Ortho-anthranilamide derivatives as anti-coagulants

• US 6,140,351 A
• Filed: 11/05/1998
• Issued: 10/31/2000
• Est. Priority Date: 12/19/1997
• Status: Expired due to Fees

• Current Assignee: Bayer Schering Pharma AG (Bayer AG)
• Original Assignee: Berlex Laboratories Incorporated (Bayer AG)
• Inventors: Wu, Shung C., Ye, Bin, Zhao, Zuchun, Kochanny, Monica J., Lee, Wheeseong, Phillips, Gary B., Chou, Yuo-Ling, Sakata, Steven T., Arnaiz, Damian O., Shaw, Kenneth J., Karanjawala, Rushad E., Morrissey, Michael M., Griedel, Brian D., Snider, R. Michael, Sacchi, Karna Lyn, Liang, Amy Mei
• Primary Examiner(s): SEAMAN, D MARGARET M
• Application Number:
  US09/187,459
• Time in Patent Office: 726 Days
• Field of Search: 514/536, 546/280.4
• US Class Current: 514/336
• CPC Class Codes: C07D 333/38 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/70 attached in position 2
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 409/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 473/06 with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
• CPC Class Codes: C07D 473/34 attached in position 6, e.g. adenine

Abstract

This invention is directed to compounds of formula (III): ##STR1## wherein B, C, D, E, R¹, R² and R³ are disclosed herein. These compounds are disclosed as being useful as anti-coagulants.

Claims

1. A compound of formula (I):

##STR55## wherein;

A is =N--;

m is 1 to 3;

n is 1 to 4;

D is --N(R⁵)--C(Z)-- or --N(R⁵)--S(O)_p -- (where p is 0 to 2;

Z is oxygen, sulfur or H₂ ; and

the nitrogen atom is directly bonded to the phenyl ring having the R¹ and R² substituents);

E is --C(Z)--N(R⁵)-- or --S(O)_p --N(R⁵)-- (where p is 0 to 2;

Z is oxygen, sulfur or H₂ ; and

the nitrogen atom can be bonded to the phenyl ring having the R¹ and the R² substituents or to the aromatic ring having the R⁴ substituent);

each R¹ is independently hydrogen, alkyl, aryl, aralkyl, halo, haloalkyl, cyano, --OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --C(O)OR⁵, --C(O)N(R⁵)R⁶, --N(R⁵)R⁶, --O--C(O)R⁵, or --N(R⁵)--CH(R¹²)--C(O)OR⁵ ;

or two adjacent R¹, s together with the carbons to which they are attached form a heterocyclic ring fused to the phenyl ring wherein the heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl and aralkyl;

R² is hydrogen, alkyl, aryl, aralkyl, halo, haloalkyl, cyano, --OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --C(O)OR⁵, --OC(O)--R⁵, --C(O)N(R⁵)R⁶, --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--S(O)_p --R⁹ (where p is 0 to

     2), --C(R⁷)H--R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --O--R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --C(R⁷)H--N(R⁵)R⁶, --C(R⁷)H--R⁸ --N(R⁵)R⁶, --O--R⁸ --CH(OH)--CH₂ --N(R¹⁰)R¹¹, --O--R⁸ --N(R¹⁰)R¹¹, --O--R⁸ --O--C(O)R⁵, --O--R⁸ --CH(OH)--CH₂ --OR⁵, --O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --O--(R⁸ --O)_t --R¹⁹ (where t is 1 to

     6), --O--R⁸ --C(O)R5, --O--R⁸ --C(O)R¹⁹, --O--R⁸ --C(O)OR⁵, --N(R⁵)--R⁸ --N(R¹⁰)R¹¹, --S(O)_p --R⁸ --N(R⁵)R⁶ (where p is 0 to

     2), --S(O)_p --R⁸ --C(O)OR⁵ (where p is 0 to

     2), or --N(R⁵)--CH(R¹²)--C(O)OR⁵ ;

R³ is a radical of formula (i);

##STR56## where;

r is 1 or2;

R¹³ is hydrogen, alkyl, halo, haloalkyl, --N(R⁵)R⁶, --C(R⁷)H--N(R⁵)R⁶, O--R⁵, --R⁸ --OR⁵, --S(O)_p --R⁸ --N(R⁵)R⁶ (where p is 0 to

     2) or heterocyclylalkyl (where the heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, aralkyl, nitro and cyano); and

each R¹⁴ is independently hydrogen, alkyl, halo, formyl, acetyl, cyano, --R⁸ --CN, --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R⁷)H--N.sup.⊕

(R⁹)(R¹⁶)₂, --C(R⁷)H--R⁸ --N.sup.⊕

(R⁹)(R¹⁶)₂, --C(O)OR⁵, --C(R⁷)H--C(O)OR⁵, --C(R⁷)H--R⁸ --C(O)OR⁵, --OR⁵, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--O--R¹⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --S(O)_p --N(R⁵)R⁶ (where p is 0 to

     2), --C(O)N(R⁵)R⁶, --C(R⁷)H--C(O)N(R⁵)R⁶, --C(R⁷)H--R⁸ --C(O)N(R⁵)R⁶, --C(R⁷)H--N(R⁵)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--R⁸ --N(R⁵)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--R⁸ --O--(R⁸ --O)_t --R⁵ (where t is I to

     6), --O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--N(R⁵)--R⁸ --[CH(OH)]_t --CH₂ --OR⁵ (where t is 1 to

     6), --C(R⁷)H--N(R⁵)--S(O)₂ --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(N R¹⁷)--R¹⁰, --C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--O--N(R⁵)R⁶, heterocyclyl (wherein the heterocyclyl radical is not attached to the radical of formula (i) through a nitrogen atom and is optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (wherein the heterocyclyl radical is not attached to the alkyl radical through a nitrogen atom and is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

each R⁴ is independently hydrogen, alkyl, halo, haloalkyl, cyano, nitro, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, or --R⁸ --N(R⁵)R⁶ ;

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁷ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)p--R¹⁵ (where p is 0 to

     2), --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R¹⁵, --R⁸ --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --S(O)p--R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶);

R¹² is a side chain of an α

-amino acid;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶);

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl;

each R¹⁶ is independently alkyl, aryl, aralkyl, --R⁸ --OR⁵, --R⁸ --N(R⁵)R⁶, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

or

both R^16'"'"' s together with the nitrogen to which they are attached (and wherein the R⁹ substituent is not present) form an aromatic N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and --(R⁸ --O)_t --R⁵ (where t is 1 to

     6);

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ ;

R¹⁸ is hydrogen, alkyl, aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂ ; and

each R¹⁹ is cycloalkyl, haloalkyl, --R⁸ --OR⁵, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --R⁸ --C(O)N(R⁵)R⁶, heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

as a single stereoisomer or a mixture thereof;

or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 wherein:

A is =N--;

m is 1 to 3;

n is 1 to 4;

D is --N(R⁵)--C(Z)-- (where Z is oxygen, sulfur or H₂, and R⁵ is hydrogen or alkyl);

E is --C(Z)--N(R⁵)-- (where Z is oxygen, sulfur or H₂, R⁵ is hydrogen or alkyl, and the nitrogen is attached to the pyridinyl ring);

R¹ is halo or haloalkyl;

R² is --N(R¹⁰)R¹¹, --O--R⁸ --S(O)p--R⁹ (where p is

     0), --O--R⁸ --C(O)OR⁵, --O--(R⁸ --O)_t --R⁵ (where t is

     1) or --O--R⁸ --N(R¹⁰)R¹¹ where;

each R⁵ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene chain;

R⁹ is alkyl; and

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, or --R⁸ --O--R⁵ (where R⁸ is a straight or branched alkylene chain and R⁵ is hydrogen or alkyl);

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to one additional hetero atoms, where the N-heterocyclic ring is optionally substituted by alkyl;

R³ is a radical of the formula (i);

##STR59## where r is 1;

R¹³ is halo; and

R¹⁴ is --C(R⁷)H--N(R¹⁰)R¹¹ where;

R⁷ is hydrogen; and

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form piperazinyl optionally substituted by one or more substituents selected from the group consisting of alkyl and --C(O)R⁵ ; and

R⁴ is hydrogen or halo.

4. The compound of claim 3 wherein:

m is 1;

n is 1;

D is --N(H)--C(O)--;

E is --C(O)--N(H)-- (where the nitrogen is bonded to the 2-position of the pyridinyl ring);

R¹ is halo in the 5-position;

R² is --N(R¹⁰)R¹¹, --O--R⁸ --S(O)_p --R⁹ (where p is

     0), --O--R⁸ --C(O)OR⁵, --O--(R⁸ --O)_t --R⁵ (where t is

     1) or --O--R⁸ --N(R¹⁰)R¹¹ where;

each R⁵ is independently hydrogen, methyl or ethyl;

each R⁸ is independently a methylene, ethylene or propylene chain;

R⁹ is methyl or ethyl; and

R¹⁰ and R¹¹ are each independently hydrogen, methyl, ethyl, or --R⁸ --O--R⁵ (where R⁸ is ethylene and R⁵ is hydrogen, methyl or ethyl);

or

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to one additional hetero atoms, where the N-heterocyclic ring is optionally substituted by alkyl;

R³ is a radical of the formula (i);

##STR60## where r is 1;

R¹³ is chloro; and

R¹⁴ is in the 4-position and is --C(R⁷)H--N(R¹⁰)R¹¹ where;

R⁷ is hydrogen; and

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form piperazinyl optionally substituted by methyl or ethyl; and

R⁴ is hydrogen, bromo or chloro in the 5-position.

5. The compound of claim 4 wherein:

R¹ is chloro;

R² is --O--R⁸ --S(O)_p --R⁹ (where p is

     0), --O--R⁸ --C(O)OR⁵ or --O--(R⁸ --O)_t --R⁵ (where t is 1 or

     2) where;

each R⁵ is independently hydrogen, methyl or ethyl;

each R⁸ is independently a methylene, ethylene or propylene chain; and

R⁹ is methyl or ethyl.

6. The compound of claim 5 which is selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(methylthio)methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(ethoxycarbonyl)methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxyethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-methoxyethoxy)-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-ethoxyethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-ethylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-methoxyethoxy)-5-chlorobenzamide, and

N-(5-chloropyridin-2-yl)-2-[((4-((4-ethylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-(2-methoxyethoxy)ethoxy)-5-chlorobenzamide.

7. The compound of claim 4 wherein

R¹ is chloro;

and

R² is --N(R¹⁰)R¹¹ or --O--R⁸ --N(R¹⁰)R¹¹ where;

R⁸ is a methylene, ethylene or propylene chain; and

R¹⁰ and R¹¹ are each independently hydrogen, methyl, ethyl, or --R⁸ --O--R⁵ (where R⁸ is ethylene and R⁵ is hydrogen, methyl or ethyl).

8. The compound of claim 7 which is selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(dimethyl)amino-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(N'"'"'-methyl-N'"'"'-(2-hydroxyethyl)amino)propoxy)-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-amino-5-chlorobenzamide.

9. The compound of claim 4 wherein

R¹ is chloro;

R² is --N(R¹⁰)R¹¹ or --O--R⁸ --N(R¹⁰)R¹¹ where;

R⁸ is methylene, ethylene or propylene; and

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to one additional hetero atoms, where the N-heterocyclic ring is optionally substituted by alkyl and is selected from the group consisting of morpholinyl, piperazinyl, pyrrolidinyl or imidazolyl.

10. The compound of claim 9 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(4-methylpiperazin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-morpholinylpropoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(pyrrolidin-1-yl)propoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(pyrrolidin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(imidazol-1-yl)propoxy)-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((4-ethylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide.

11. The compound of claim 1 wherein:

A is =N--;

m is 1 to 3;

n is 1 to 4;

D is --N(R⁵)--C(Z)--(where Z is oxygen, sulfur or H₂, and R⁵ is hydrogen or alkyl);

E is --C(Z)--N(R⁵)--(where Z is oxygen, sulfur or H₂, R⁵ is hydrogen or alkyl, and the nitrogen is attached to the pyridinyl ring);

R¹ is halo or haloalkyl;

R² is hydrogen, haloalkyl, or --OR⁵ where R⁵ is hydrogen or alkyl;

R³ is a radical of the formula (i);

##STR61## where r is 1;

R¹³ is halo; and

each R¹⁴ is independently hydrogen, alkyl, halo, formyl, acetyl, cyano, --R⁸ --CN, --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R⁷)H--N.sup.⊕

(R⁹)(R¹⁶)₂, --C(R⁷)H--R⁸ --N.sup.⊕

(R⁹)(R¹⁶)₂, --C(O)OR⁵, --C(R⁷)H--C(O)OR⁵, --C(R⁷)H--R⁸ --C(O)OR⁵, --OR⁵, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--O--R¹⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --S(O)_p --N(R⁵)R⁶ (where p is 0 to

     2), -C(O)N(R⁵)R⁶, --C(R⁷)H--C(O)N(R⁵)R⁶, --C(R⁷)H--R⁸ --C(O)N(R⁵)R⁶, --C(R⁷)H--N(R⁵)--(R⁸ -O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--R--N(R⁵)-(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--R⁸ --O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--N(R⁵)--R⁸ --[CH(OH)]_t --CH₂ --OR⁵ (where t is 1 to

     6), --C(R⁷)H--N(R⁵)--S(O)₂ --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--R¹⁰, --C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--O--N(R⁵)R⁶, heterocyclyl (wherein the heterocyclyl radical is not attached to the radical of formula (i) through a nitrogen atom and is optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (wherein the heterocyclyl radical is not attached to the alkyl radical through a nitrogen atom and is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

where R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁷ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --N(R )R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R¹⁵, R⁸ --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R₁₅, --C(O)O--R --N(R⁸)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)p--R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)p--R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl,

--R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶,

--R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl, where

each R⁵ is hydrogen, alkyl, aryl or aralkyl; and

R¹⁸ is hydrogen, alkyl, aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂ ;

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t R⁵ (where t is 1 to

     6), --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶, where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R¹⁶ is independently alkyl, aryl, aralkyl, --R --OR⁵, --R⁸ --N(R⁵)R⁶, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

or

both R¹⁶, s together with the nitrogen to which they are attached (and wherein the R⁹ substituent is not present) form an aromatic N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and --(R⁸ --O)_t --R⁵ (where t is 1 to

     6), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶, where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

and R⁴ is hydrogen or halo.

12. The compound of claim 11 wherein:

m is 1;

n is 1;

D is --N(H)--C(O)--;

E is --C(O)--N(H)-- (where the nitrogen is bonded to the 2-position of the pyridinyl ring);

R² is hydrogen, haloalkyl, or --OR⁵ where R⁵ is hydrogen or alkyl;

R³ is a radical of the formula (i);

##STR62## where r is 1;

R¹³ is halo; and

R is --C(R⁷)H--N(R¹⁰)R¹¹ where;

R⁷ is hydrogen;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R⁵, --R--C(O)--N(R⁵)R¹⁵,--C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alky, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)p--R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R8--S(O)p--R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl, where

each R⁵ is hydrogen, alkyl, aryl or aralkyl; and

R¹⁸ is hydrogen, alkl, aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂ ;

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

and R⁴ is in the 5-position.

13. The compound of claim 12 wherein:

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)p--R¹⁵ (where p is 0 to

     2), --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R¹⁵, --R⁸ --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)p--R9 (where p is 0 to

     2), --R⁸ --S(O)_p R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R9 (where p is 0 to

     2), --R --S(O)p--R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R6 are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R--OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶) where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl, where

each R⁵ is independently hydrogen, alkyl, aryl or aralkyl; and

R¹⁸ is hydrogen, alkyl, aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂.

14. The compound of claim 13 wherein:

R¹⁰ is hydrogen, alkyl, or --R⁸ --OR⁵ ; and

R¹¹ is hydrogen, alkyl or --R⁸ --OR⁵ ;

where each R⁸ is independently a straight or branched alkylene chain, and each R⁵ is hydrogen or alkyl.

15. The compound of claim 14 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-hydroxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'N'"'"'-di(2-hydroxypropyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(3-hydroxypropyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxypropyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2,2-dimethyl-2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-ethoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(((2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(amino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((dimethylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(1-methylethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(ethylamino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-(diethylamino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

16. The compound of claim 13 wherein:

R¹⁰ is hydrogen, alkyl, or --R⁸ --N(R⁵)R⁶, and

R¹¹ is --S(O)_p --R¹⁵ (where p is 0 to

     2) or --R⁸ --N(R⁵)R⁶ where;

R⁵ and R⁶ are independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain; and

R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶) where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain.

17. The compound of claim 16 selected from the group consisting of.

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(3-(dimethylamino)propyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(dimethylamino)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-hydroxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(methyl)sulfonyl--N'"'"'-(2-(dimethylamino)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(dimethylamino)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((3,5-dimethylisoxazol4-yl)sulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-hydroxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'- ((2-(4-hydroxypiperidin-1-yl)ethyl)sulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((2-(pyrrolidin-1-yl)ethyl)sulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((Nt-methyl--N'"'"'-((dimethylamino)sulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2-aminoethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(4-(dimethylamino)but-3-yn-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

18. The compound of claim 13 wherein:

R10 is hydrogen, alkyl or --R⁸ --OR⁵ ; and

R¹¹ is formyl, cyano, --C(O)--R¹⁵, --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R¹⁵, --R⁸ (R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, or --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

R⁸ is a straight or branched alkylene chain;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶) where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain; and

R¹⁸ is hydrogen, alkyl aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂.

19. The compound of claim 18 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N"-ethylureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N"-(2-carboxyethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((4-(2-hydroxyethyl)piperazin-1-yl)carbonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N"-(2-(morpholin-4-yl)ethyl)thioureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(((4-hydroxypiperidin-1-yl)methyl)carbonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N"-(2-hydroxyethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(N'"'"'-methylureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2-hydroxyethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N"-(2-(chloro)ethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N"-(2-(acetoxy)ethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N"-(2-(pyrrolidin-1-yl)ethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N"-(2-(chloro)ethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(((2-hydroxyphenyl)carbonyl)oxy)ethyl)ureido)-methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-cyanoamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2-((fluoromethylcarbonyl)amino)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((2-aminoethoxy)carbonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((methylthio)carbonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-((phenylthio)carbonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-nitro-1-(methylamino)ethenyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(((2-dimethylphosphoramidoethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

20. The compound of claim 13 wherein:

R¹⁰ is hydrogen, alkyl, haloalkyl, or --R⁸ --OR⁵ ;

R¹¹ is cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain; and

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶) where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain.

21. The compound of claim 20 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2-(morpholin-4-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(1-methylpiperidin-4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-hydroxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(4-hydroxycyclohexyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(pyridin-2-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(thiazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(thiazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(4-(oxo)oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(pyridin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(dihydro-4(H)-1,3-oxazin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--Nt-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-hydroxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(t-butyl)--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(((thiazol-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2-methoxyethyl)-

N-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(oxazol-2-yl)amino)methyl)-3-chiorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N- (4-trifluoromethyl-5-(methoxycarbonyl)pyrimidin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(dihydro-4(H)-1,3-oxazin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N-methyl--Nt-(5-methyloxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(tetrazol-5-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N (tetrazol-5-yl)amino)methyl-3-chiorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(4-methyloxazolin-2-yl)amino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(pyrazol-3-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2,2,2-trifluoroethyl)--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(4-(ethoxycarbonyl)oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((Nt-(3,4-dihydro-2H-pyrrol-5-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(1,2,4-triazol4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(3,4-dihydro-2H-pyrrol-5-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl-N-(pyridin-4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N!-(2-amino-6-methylpyrimidin-4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((1,2,4-oxadiazol-3-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2-(imidazol-4-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-y)-2-[((4-((N'"'"'-methyl--N'"'"'-(3,4,5,6-tetrahydropyridin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-chloropyrimidin-4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'ethyl--N'"'"'-((imidazol-2-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(4-aminopyrimidin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide

N-(5-chloropyridin-2-yl)-2-[((4-((Nt-(4-aminopyrimidin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(4-(methylamino)pyrimidin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((3-(methoxymethyl)-1,2,4-oxadiazol-5-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((3-((methylthio)methyl)-1,2,4-oxadiazol-5-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(1,3,2-dioxaphospholan-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

22. The compound of claim 12 wherein:

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --S(O)p--R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ --O),R⁵ (where t is 1 to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain.

23. The compound of claim 22 wherein the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, and nitro.

24. The compound of claim 23 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((4,5-dihydropyrazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((imidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((morpholin-4-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((pyrazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((hydantoin-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((1,4,5,6-tetrahydropyrimidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((pyrrolidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2,3,4,5,6,7-hexahydro-3,7-dimethyl-2,6-dioxo-1H-purin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-hydroxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide;

N-(pyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide;

N-(5-bromopyridin-2-yl)-2-[((4-((4-methylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-ethylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-methylimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-methylimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((5-methylimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-methylimidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2,4-dimethylimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2,5-dimethylimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-methyl-4-nitroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4,5-dichloroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(chloromethyl)imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((2-(fluoromethyl)imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

25. The compound of claim 22 wherein the N-heterocylic ring is substituted by one or more substituents selected from the group consisting of alkyl, nitro, --R⁸ --CN, --OR⁵, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --S(O)_p --R⁹ (where p is 0 to 2), --(R⁸ --O)_t R⁵ (where t is 1 to 6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl.

26. The compound of claim 25 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((4-(hydroxymethyl)imidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((5-(hydroxymethyl)imidazol-1-yl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(methoxymethyl)imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(hydroxymethyl)imidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-formylpiperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(N amino--N'"'"'-methylamino)imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-hydroxypiperidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(methylthio)imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-(methylsulfonyl)piperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-methyl-4-nitroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(cyanomethyl)imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((4-(pyrimidin-2-yl)piperazin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

27. The compound of claim 22 wherein the N-heterocylic ring is substituted by one or more substituents selected from the group consisting of alkyl, oxo, --OR⁵ =N(R¹⁷), --C(O)OR⁵, --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --(R⁸ --O)_t R⁵, and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, or --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, --R⁸ --C(O)--N(R⁵)R⁶ where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain.

28. The compound of claim 27 wherein the N-heterocylic ring is substituted by =N(R¹⁷) and is optionally substituted by one or more substituents selected from the group consisting of alkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, and --(R⁸ --O)_t --R⁵, where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain.

29. The compound of claim 28 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-5-methyltetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-5,5(dimethyl)tetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-ethylimino-5,5-(dimethyl)tetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2- imino-5,5-methyltetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-5(S)-methyltetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino tetrahydrooxazol -3-yl) methyl)-3-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-iminotetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-4-methyltetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((trans4,5-dimethyl-2-iminotetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((cis4,5-dimethyl-2-iminotetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((3-methyl-2-imino-2,3-dihydroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-tetrahydroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-1 ,2-dihydropyrimidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-4-(hydroxymethyl)tetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-iminotetrahydrothiazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-4-oxoimidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((tetrahydro-2-imino-2H-pyrimidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(methoxycarbonylamino)imidazolin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(cyanoimino)tetrahydroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-3-((phenylamino)carbonyl)tetrahydroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((cis4,5-dimethoxy-2-iminotetrahydroimidazol-l -yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-amino4-imino-1,4-dihydropyrimidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-((2-hydroxyethyl)imino)tetrahydroimidazol-l -yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-iminopiperidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-imino-1 (4H)-pyridinyl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-1 (2M)-pyridin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(ethylimino)pyrrolidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((2-(((aminocarbonyl)methyl)imino)tetrahydroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

30. The compound of claim 22 wherein the N-heterocylic ring is substituted by --N(R⁵)R⁶ and optionally substituted by one or more substituents selected from the group consisting of alkyl, oxo, --N(R⁵)R⁶, --OR⁵, and --C(O)N(R⁵)R⁶, where R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl.

31. The compound of claim 30 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((2-aminoimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((5-aminotetrazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((3-amino-1 ,2,4-triazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((3,5-diamino-4H-1 ,2,4-triazol-4-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((4-amino-5-(aminocarbonyl)imidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2,6-diaminopurin-9-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2,6-diaminopurin-7-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((5-amino-2-oxo-2H-pyrimidin-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((6-aminopurin-9-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((6-aminopurin-7-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-amino-6-oxopurin-9-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-amino-6-oxopurin-7-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((5-(dimethylamino)-1 ,2,4-oxadiazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((5-amino-1 ,2,4-oxadiazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(methylamino)imidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2,4-diamino-6-hydroxypyrimidin-5-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(ethylamino)imidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-(1-methylethyl)aminolmidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((3-dimethylamino-5-methylpyrazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((3-dimethylamino-5-methylpyrazol-2-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

32. The compound of claim 11 wherein:

each R¹⁴ is independently alkyl, --R⁸ --CN, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N.sup.⊕

(R⁹)(R¹⁶)₂, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--O--R¹⁵, --C(R⁷)H--S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--N(R⁵)--(R⁵)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--N(R⁵)--R⁸ --[CH(OH)]_t CH₂ --OR⁵ (where t is 1 to

     6), --C(R⁷)H--N(R⁵)--S(O)₂ --N(R¹⁰)R¹¹, --C(R⁷)H--O--N(R⁵)R⁶, or heterocyclyl (wherein the heterocyclyl radical is not attached to the radical of formula (i) through a nitrogen atom and is optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁷ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁵ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R¹⁵, --R⁸ --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl, where

each R⁵ is hydrogen, alkyl, aryl or aralkyl; and

R¹⁸ is hydrogen, alkyl, aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂ ;

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶, where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R¹⁶ is independently alkyl, aryl, aralkyl, --R⁸ --OR⁵, --R⁸ --N(R⁵)R⁶, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

or

both R16,s together with the nitrogen to which they are attached (and wherein the R⁹ substituent is not present) form an aromatic N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, --OR⁵, --R⁸ OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O),R⁵ (where t is 1 to

     6), and --(R⁸ --O)_t --R⁵ (where t is I to

     6), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain.

33. The compound of claim 32 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((pyridinium-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-hydroxy-5-chlorobenzamide,

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(hydroxyethoxy)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((methylsulfinyl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2,3-dihydroxypropyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(((2-hydroxyethyl)sulfinyl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((pyridinium-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-cyanomethyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(2-methylaminoethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(hydroxy)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(((imidazol-2-yl)thio)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((imidazolin-2-yl)thio)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(((5-hydroxymethyl-1-methylimidazol-2-yl)thio)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(((diethylamino)oxy)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-(imidazolin-2-yl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

34. The compound of claim 11 wherein:

each R¹⁴ is independently --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--N(R¹⁰)R¹¹ --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--R¹⁰, or --C(R⁷)H--C(NR¹⁷)--N(R⁵)R⁶, where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁷ is independently hydrogen or alkyl;

each R⁹ is independently alkyl, aryl or aralkyl;

R¹⁰ and R¹ " are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)p--R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R¹⁵, --R⁸ --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)--P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)p--R9 (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR , --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl, where

each R⁵ is hydrogen, alkyl, aryl or aralkyl; and

R¹⁸ is hydrogen, alkyl, aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂ ;

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), where

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R8 is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶, where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶, where

R⁵ and R⁶ are independently each hydrogen, alkyl, aryl or aralkyl, and

each R8 is independently a straight or branched alkylene, alkylidene or alkylidyne chain.

35. The compound of claim 34 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-(((amidino)(methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(1-iminoethyl)--N'"'"'-methylamino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(N'"'"',N"-dimethyl--N'"'"'"-cyanoguanidino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(N'"'"'-methyl-N"-hydroxyguanidino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(N'"'"'-methyl-N"-(2-aminoethyl)-N'"'"'"-cyanoguanidino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(N'"'"'-methyl-N"-aminoguanidino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-(N'"'"',N"-dimethyl--N'"'"'"-(aminocarbonyl)guanidino)methyl-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(imino(phenyl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(i-imino-2-(aminocarbonyl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(1-imino4,4,4-trifluorobutyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(imino(pyridin4-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(imino(thiophen-2-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(imino(pyrazin-2-yl)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(cyclopropyl(imino)methyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(3-cyano-1-iminopropyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(1-imino-4,4,4-trifluorobutyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-(2-amino-2-(hydroxylmino)ethyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide.

36. The compound of claim 1 wherein:

A is =N--;

m is 1;

n is 1;

D is --N(H)--C(O)--;

E is --C(O)--N(H)-- (where the nitrogen is bonded to the 2-position of the pyridinyl ring);

R² is --N(R¹⁰)R¹¹ where;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl or --R⁸ --O--R⁵ where R⁸ is an alkylene chain, and R⁵ is hydrogen or alkyl;

or

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl and --C(O)OR⁵ where R⁵ is hydrogen or alkyl;

R³ is a radical of the formula (i);

##STR63## where r is 1;

R¹³ is halo; and

R¹⁴ is --C(R⁷)H--N(R¹⁰)R¹¹ or --C(R⁷)H--N(R⁵)--R⁸ --[CH(OH)]_t --CH₂ --OR⁵ (where t is 1 to

     3)

where;

each R⁵ is independently hydrogen or alkyl;

R⁷ is hydrogen;

R⁸ is a straight or branched alkylene chain;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, formyl, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --C(S)NH₂, --C(O)--N(R⁵)R¹¹, --C(S)--N(R⁵)R¹⁵, cycloalkyl (optionally substituted by --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵), where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene chain; and

each R¹⁵ is alkyl, --R⁸ --OR⁵, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by --R⁸ --OR⁵), or heterocyclylalkyl (optionally substituted by --OR⁵);

or R¹⁰ and R¹⁰ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, oxo, =N(R¹⁷), --OR⁵, --R⁸ --OR⁵, and --N(R⁵)R⁶ ;

where

each R⁵ and R⁶ is independently hydrogen or alkyl;

R⁸ is a straight or branched alkylene chain; and

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ ;

and R⁴ is in the 5-position and is hydrogen or halo.

37. The compound of claim 36 wherein:

R² is --N(R¹⁰)R¹¹ where;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl or --R⁸ --O--R⁵ where R⁸ is an alkylene chain, and R⁵ is hydrogen or alkyl.

38. The compound of claim 37 wherein:

R¹⁴ is --C(R⁷)H--N(R¹⁰)R¹¹ where;

R⁷ is hydrogen;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, formyl, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --C(S)NH₂, --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, cycloalkyl (optionally substituted by --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alky, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵);

where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene chain; and

each R¹⁵ is alkyl, --R⁸ --OR⁵, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by --R⁸ --OR⁵), or heterocyclylalkyl (optionally substituted by --OR⁵);

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, oxo, =N(R¹⁷), --OR⁵, --R⁸ --OR⁵, and --N(R⁵)R⁶ ;

where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

R⁸ is straight or branched alkylene chain; and

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶.

39. The compound of claim 38 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(3-(dimethylamino)propyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(dimethyl)amino-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(dimethylamino)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(dimethyl)amino-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(1-methylpiperidin4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(dimethyl)amino-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N (2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(di(2-methoxyethyl)amino)-5-chlorobenzamide.

40. The compound of claim 36 wherein

R² is --N(R¹⁰)R¹¹ where:

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl and --C(O)OR⁵ where R⁵ is hydrogen or alkyl.

41. The compound of claim 40 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl-N-(2-(dimethylamino)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(1-methylpiperidin-4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(morpholin-4-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl-N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl-N'"'"'-(3-(dimethylamino)propyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropynidin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-methoxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methylsulfonyl--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)ureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(4-methylpiperazin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(4-methylpiperazin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl-N-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(pyrrolidin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-(1-methylethyl)--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(4-(ethoxycarbonyl)piperidin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--Nt-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(4-(carboxy)piperidin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--Nt-(2,3-dihydroxypropyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-ethylureido)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(4-ethylpiperazin-1-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--Nt-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((Nt-methyl--Nt-(4-trifluoromethyl-5-(methoxycarbonyl)pyrimidin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(4-trifluoromethyl-5-carboxypyrimidin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin-4-yl)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((2-iminotetrahydrooxazol-3-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin4-yl)-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(tetrazol-5-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(morpholin4-yl)-5-chlorobenzamide.

42. The compound of claim 1 wherein:

A is =N--;

m is 1;

n is 1;

D is --N(H)--C(O)--;

E is --C(O)--N(H)-- (where the nitrogen is bonded to the 2-position of the pyridinyl ring);

R² is --O--(R⁸ --O)_t R⁵ (where t is 1 to

     3) or --O--(R⁸ --O)_t --R¹⁹ where R⁵ is hydrogen or alkyl, each R⁸ is independently a straight or branched alkylene chain, and R¹⁹ is heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, or haloalkyl);

R³ is a radical of the formula (i);

##STR64## where r is 1;

R¹³ is halo; and

R¹⁴ is --C(R⁷)H--N(R¹⁰)R¹¹ or --C(R⁷)H--N(R⁵)--R⁸ --[CH(OH)], --CH₂ --OR⁵ (where t is 1 to

     6) where;

each R⁵ is independently hydrogen or alkyl;

R⁸ is a straight or branched alkylene chain;

R⁷ is hydrogen;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, formyl, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --C(S)NH₂, --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, cycloalkyl (optionally substituted by --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵);

where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene chain; and

each R¹⁵ is alkyl, --R⁸ --OR⁵, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by --R⁸ --OR⁵), or heterocyclylalkyl (optionally substituted by --OR⁵);

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, oxo, =N(R¹⁷), --OR⁵, --R⁸ --OR⁵, and --N(R⁵)R⁶ ;

where

each R⁵ and R⁶ is independently hydrogen or alkyl;

R⁸ is straight or branched alkylene chain; and

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ ; and

R⁴ is in the 5-position and is hydrogen or halo.

43. The compound of claim 42 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(dimethylamino)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxyethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(1-methylpiperidin-4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxyethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-methoxyethoxy)-5-chlorobenzamide,

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxyethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2,3-dihydroxypropyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-methoxyethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-ethyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-methoxyethoxy)-5-chlorobenzamide,

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-methoxyethoxy)-5-chlorobenzamide,

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-((2-(2-methoxyethoxy)ethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-((2-(2-methoxyethoxy)ethoxy)-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--Nt-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(pyridin-3-yloxy)propoxy)-5-chlorobenzamide.

44. The compound of claim 1 wherein:

A is =N--;

m is 1;

n is 1;

D is --N(H)--C(O)--;

E is --C(O)--N(H)-- (where the nitrogen is bonded to the 2-position of the pyridinyl ring);

R² is --O--R --N(R¹⁰)R¹¹ where;

R⁸ is a straight or branched alkylene chain; and

R¹⁰ and R¹¹ are each independently hydrogen, alkyl or --R⁸ --O--R⁵ where R⁸ is an alkylene chain, and R⁵ is hydrogen or alkyl;

or

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl and --C(O)OR⁵ where R⁵ is hydrogen or alkyl;

R³ is a radical of the formula (i);

##STR65## where r is 1;

R¹³ is halo; and

R¹⁴ is --C(R⁷)H--N(R¹⁰)R¹¹ where;

R⁷ is hydrogen;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, formyl, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R₁₅, --C(O)NH₂, --C(S)NH₂, --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, cycloalkyl (optionally substituted by --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵ and --C(O)OR⁵), where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene chain; and

each R¹⁵ is alkyl, --R⁸ --OR⁵, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by --R⁸ --OR⁵), or heterocyclylalkyl (optionally substituted by --OR⁵); and

R⁴ is in the 5-position and is hydrogen or halo.

45. The compound of claim 44 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(1-methylpiperidin-4-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(morpholin-4-yl)propoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(pyrrolidin-1-yl)propoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(morpholin-4-yl)propoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-(imidazol-1-yl)ethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(imidazol-I -yl)propoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-(pyrrolidin-1-yl)ethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-(imidazol-I -yl)ethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-(pyrrolidin-1-yl)ethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--Nt-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(3-(4-ethylpiperazin-1-yl)propoxy)-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-aminoethoxy)-5-chlorobenzamide.

46. The compound of claim 1 wherein:

A is =N--;

m is 1;

n is 1;

D is --N(H)--C(O)--;

E is --C(O)--N(H)-- (where the nitrogen is bonded to the 2-position of the pyridinyl ring);

R² is --O--R⁸ --O--C(O)R⁵, --O--R⁸ --CH(OH)--CH₂ --N(R¹⁰)R¹¹, or --O--R⁸ --CH(OH)--CH₂ --OR⁵ where

each R⁵ is hydrogen or alkyl;

R⁸ is a straight or branched alkylene chain; and

R¹⁰ and R¹¹ are each independently hydrogen, alkyl or --R⁸ --O--R⁵ where R⁸ is an alkylene chain, and R⁵ is hydrogen or alkyl;

or

R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocylic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl and --C(O)OR⁵ where R⁵ is hydrogen or alkyl;

R³ is a radical of the formula (i);

##STR66## where r is 1;

R¹³ is halo; and

R¹⁴ is --C(R⁷)H--N(R¹⁰)R¹¹ or --C(R⁷)H--N(R⁵)--S(O)₂ --N(R¹⁰)R¹¹ where;

R⁵ is hydrogen or alkyl;

R⁷ is hydrogen;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, formyl, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --C(S)NH₂, --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, cycloalkyl (optionally substituted by --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵);

where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene chain; and

each R is alkyl, --R⁸ --OR⁵, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by --R⁸ --OR⁵), or heterocyclylalkyl (optionally substituted by --OR⁵); and

R⁴ is in the 5-position and is hydrogen or halo.

47. The compound of claim 46 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-(pyrrolidin-1-yl)ethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-acetoxyethoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl-N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-((dimethylamino)sulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-5-chlorobenzamide;

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxy-3-(imidazol-1-yl)propoxy)-5-chlorobenzamide; and

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(methylsulfonyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-(2-hydroxy-3-methoxypropoxy)-5-chlorobenzamide.

48. The compound of claim 1 wherein:

A is =N--;

m is 1 to 3;

n is 1;

D is --N(R⁵)--C()--(where Z is oxygen and R⁵ is hydrogen or alkyl);

E is --C(Z)--N(R⁵)--(where Z is oxygen, R⁵ is hydrogen or alkyl, and the nitrogen is attached to the pyridinyl ring);

each R¹ is independently hydrogen, halo or --OR⁵ ;

or two adjacent R^1'"'"' s together with the carbons to which they are attached form a dioxole ring fused to the phenyl ring wherein the dioxole ring is optionally substituted by alkyl;

R² is hydrogen;

R³ is a radical of the formula (i);

##STR67## where r is 1;

R¹³ is halo; and

R¹⁴ is --C(R⁷)H--N(R¹⁰)R¹¹ where;

R⁷ is hydrogen; and

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, formyl, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --C(S)NH₂, --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, cycloalkyl (optionally substituted by --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵), or heterocyclyalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, haloalkyl, oxo, --OR⁵, and --C(O)OR⁵);

where;

each R⁵ and R⁶ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene chain; and

each R¹⁵ is alkyl, --R⁸ --OR⁵, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by --R⁸ --OR⁵), or heterocyclyalkyl (optionally substituted by --OR⁵); and

R⁴ is in the 5-position and is hydrogen or halo.

49. The compound of claim 48 selected from the group consisting of:

N-(5-chloropyridin-2-yl)-2-[((4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3,4,5-trimethoxybenzamide;

5-(N-(5-chloropyridin-2-yl)amino)carbonyl-6-[4-((N'"'"'-methyl--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl]amino-1 ,3-benzodioxole;

5-(N-(5-chloropyridin-2-yl)amino)carbonyl-6-[4-((N'"'"'-methyl--N'"'"'-(2-hydroxyethyl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl]amino-1,3-benzodioxole; and

5-(N-(5-chloropyridin-2-yl)amino)carbonyl-6-[4-((N'"'"'-(2-methoxyethyl)--N'"'"'-(oxazolin-2-yl)amino)methyl)-3-chlorothiophen-2-yl)carbonyl]amino-1,3-benzodioxole.

2. A pharmaceutical composition useful in treating a human having a disease-state characterized by thrombotic activity, which composition comprises a pharmaceutically acceptable excipient and a therapeutically effective amount of a compound of formula (I):

##STR57## wherein;

A is =N--;

m is 1 to 3;

n is 1 to 4;

D is --N(R⁵)--C(Z)-- or --N(R⁵)--S(O)_p --(where p is 0 to 2;

Z is oxygen, sulfur or H₂ ; and

the nitrogen atom is directly bonded to the phenyl ring having the R¹ and R² substituents);

E is --C(Z)--N(R⁵)-- or --S(O)_p --N(R⁵)--(where p is 0 to 2;

Z is oxygen, sulfur or H₂ ; and

the nitrogen atom can be bonded to the phenyl ring having the R¹ and the R² substituents or to the aromatic ring having the R⁴ substituent);

each R¹ is independently hydrogen, alkyl, aryl, aralkyl, halo, haloalkyl, cyano, --OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --C(O)OR⁵, --C(O)N(R⁵)R⁶, --N(R⁵)R⁶, --O--C(O)R⁵, or --N(R⁵)--CH(R¹²)--C(O)OR⁵ ;

or two adjacent R¹, s together with the carbons to which they are attached form a heterocyclic ring fused to the phenyl ring wherein the heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl and aralkyl;

R² is hydrogen, alkyl, aryl, aralkyl, halo, haloalkyl, cyano, --OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --C(O)OR⁵, --OC(O)--R⁵, --C(O)N(R⁵)R⁶, --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--S(O)_p --R⁹ (where p is 0 to

     2), --C(R⁷)H--R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --O--R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --C(R⁷)H--N(R⁵)R⁶, --C(R⁷)H--R⁸ --N(R⁵)R⁶, --O--R⁸ --CH(OH)--CH₂ --N(R¹⁰)R¹¹, --O--R⁸ --N(R¹⁰)R¹¹, --O--R⁸ --O--C(O)R⁵, --O--R⁸ --CH(OH)--CH₂ --OR⁵, --O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --O--(R⁸ --O)_t --R¹⁹ (where t is 1 to

     6), --O--R⁸ --C(O)R⁵, --O--R⁸ --C(O)R¹⁹, --O--R⁸ --C(O)OR⁵, --N(R⁵)--R⁸ --N(R¹⁰)R¹¹, --S(O)_p --R⁸ --N(R⁵)R⁶ (where p is 0 to

     2), --S(O)p--R⁸ --C(O)OR⁵ (where p is 0 to

     2), or --N(R⁵)--CH(R¹²)--C(O)OR⁵ ;

R³ is a radical of formula (i);

##STR58## where;

r is 1 or 2;

R¹³ is hydrogen, alkyl, halo, haloalkyl, --N(R⁵)R⁶, --C(R⁷)H--N(R⁵)R⁶, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R⁸ --N(R⁵)R⁶ (where p is 0 to

     2) or heterocyclylalkyl (where the heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, aralkyl, nitro and cyano); and

each R¹⁴ is independently hydrogen, alkyl, halo, formyl, acetyl, cyano, --R⁸ --CN, --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R7)H--N.sup.⊕

(R⁹)(R¹⁶)₂, --C(R⁷)H--R⁸ --N.sup.⊕

(R⁹)(R¹⁶)₂, --C(O)OR⁵, --C(R⁷)H--C(O)OR⁵, --C(R⁷)H--R⁸ --C(O)OR⁵, --OR⁵, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--O--R¹⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --S(O)_p --N(R⁵)R⁶ (where p is 0 to

     2), --C(O)N(R⁵)R⁶, --C(R⁷)H--C(O)N(R⁵)R⁶, --C(R⁷)H--R⁸ --C(O)N(R⁵)R⁶, --C(R⁷)H--N(R⁵)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--R⁸ --N(R⁵)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--R⁸ --O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--N(R⁵)--R⁸ -[CH(OH)]_t --CH₂ --OR⁵ (where t is 1 to

     6), --C(R⁷)H--N(R⁵)--S(O)₂ --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--R¹⁰, --C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--O--N(R⁵)R⁶, heterocyclyl (wherein the heterocyclyl radical is not attached to the radical of formula (i) through a nitrogen atom and is optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (wherein the heterocyclyl radical is not attached to the alkyl radical through a nitrogen atom and is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

each R⁴ is independently hydrogen, alkyl, halo, haloalkyl, cyano, nitro, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, or --R⁸ --N(R⁵)R⁶ ;

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁷ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --N(R⁵)R⁶, --R⁸ --N(R⁵)R, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O--S--R⁵, --C(O)--N(R⁵)R¹⁵, --R⁸ --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶);

R¹² is a side chain of an α

-amino acid;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶);

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl;

each R¹⁶ is independently alkyl, aryl, aralkyl, --R⁸ --OR⁵, --R⁸ --N(R⁵)R⁶, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

or

both R^16'"'"' s together with the nitrogen to which they are attached (and wherein the R⁹ substituent is not present) form an aromatic N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, --OR⁵, --C(O)OR⁵, R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and --(R⁸ --O)_t --R⁵ (where t is 1 to

     6);

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ ;

R¹⁸ is hydrogen, alkyl, aryl, aralkyl, cyano, --C(O)OR⁵, or --NO₂ ; and

each R¹⁹ is cycloalkyl, haloalkyl, --R⁸ --OR⁵, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --R⁸ --C(O)N(R⁵)R⁶, heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

as a single stereoisomer or a mixture thereof;

or a pharmaceutically acceptable salt thereof.

50. A method of treating a human having a disease-state characterized by thrombotic activity, wherein the method comprises administering to a human in need thereof a therapeutically effective amount of a compound of formula (I):

##STR68## wherein;

A is =N--;

m is 1 to 3;

n is 1 to 4;

D is --N(R⁵)--C(Z)-- or --N(R⁵)--S(O)_p -- (where p is 0 to 2;

Z is oxygen, sulfur or H₂ ; and

the nitrogen atom is directly bonded to the phenyl ring having the R¹ and R² substituents);

E is --C(Z)--N(R⁵)-- or --S(O)_p --N(R⁵)--(where p is 0 to 2;

Z is oxygen, sulfur or H₂ ; and

the nitrogen atom can be bonded to the phenyl ring having the R¹ and the R² substituents or to the aromatic ring having the R⁴ substituent);

each R¹ is independently hydrogen, alkyl, aryl, aralkyl, halo, haloalkyl, cyano, --OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --C(O)OR⁵, --C(O)N(R⁵)R⁶, --N(R⁵)R⁶, --O--C(O)R⁵, or --N(R⁵)--CH(R¹²)--C(O)OR⁵ ;

or two adjacent R¹, s together with the carbons to which they are attached form a heterocyclic ring fused to the phenyl ring wherein the heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl and aralkyl;

R² is hydrogen, alkyl, aryl, aralkyl, halo, haloalkyl, cyano, --OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --C(O)OR⁵, --OC(O)--R⁵, --C(O)N(R⁵)R⁶, --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--S(O)_p --R⁹ (where p is 0 to

     2), --C(R⁷)H--R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --O--R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --C(R⁷)H--N(R⁵)R⁶, --C(R⁷)H--R⁸ --N(R⁵)R⁶, --O--R⁸ --CH(OH)--CH₂ --N(R¹⁰)R¹¹, --O--R⁸ --N(R¹⁰)R¹¹, --O--R⁸ --O--C(O)R⁵, --O--R⁸ --CH(OH)--CH₂ --OR⁵, --O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --O--(R⁸ --O)_t --R¹⁹ (where t is 1 to

     6), --O--R⁸ --C(O)R⁵, --O--R⁸ --C(O)R¹⁹, --O--R⁸ --C(O)OR⁵, --N(R⁵)--R⁸ --N(R¹⁰)R¹¹, --S(O)_p --R⁸ --N(R⁵)R⁶ (where p is 0 to

     2), --S(O)_p --R⁸ --C(O)OR⁵ (where p is 0 to

     2), or --N(R⁵)--CH(R¹²)--C(O)OR⁵ ;

R³ is a radical of formula (i);

##STR69## where;

r is 1 or 2;

R¹³ is hydrogen, alkyl, halo, haloalkyl, --N(R⁵)R⁶, --C(R⁷)H--N(R⁵)R⁶, OR⁵, --R^8--OR5, --S(O)_p --R⁸ --N(R⁵)R⁶ (where p is 0 to

     2) or heterocyclylalkyl (where the heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, aralkyl, nitro and cyano); and

each R¹⁴ is independently hydrogen, alkyl, halo, formyl, acetyl, cyano, --R⁸ --CN, --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)R¹¹, --C(R⁷)H--R⁸ --N(R¹⁰)R¹¹, --C(R⁷)H--N.sup.⊕

(R⁹)(R¹⁶)₂, --C(R⁷)H--R⁸ --N.sup.⊕

(R⁹)(R¹⁶)₂, --C(O)OR⁵, --C(R⁷)H--C(O)OR⁵, --C(R⁷)H--R⁸ --C(O)OR⁵, --OR⁵, --C(R⁷)H--OR⁵, --C(R⁷)H--R⁸ --OR⁵, --C(R⁷)H--O--R¹⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--S(O)_p --R¹⁵ (where p is 0 to

     2), --C(R⁷)H--R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --S(O)_p --N(R⁵)R⁶ (where p is 0 to

     2), --C(O)N(R⁵)R⁶, --C(R⁷)H--C(O)N(R⁵)R⁶, --C(R⁷)H--R⁸ --C(O)N(R⁵)R⁶, --C(R⁷)H--N(R⁵)--(R⁸ --O)t--R⁵ (where t is 1 to

     6), --C(R⁷)H--R⁸ --N(R⁵)--(R⁸ -O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --C(R⁷)H--R --O--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--O--R⁸ --CH(OH)--CH₂ --OR⁵, --C(R⁷)H--N(R⁵)--R⁸ -[CH(OH)]_t --CH₂ --OR⁵ (where t is 1 to

     6), --C(R⁷)H--N(R⁵)--S(O)₂ --N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--N(R¹⁰)R¹¹, --C(R⁷)H--N(R¹⁰)--C(NR¹⁷)--R¹⁰, --C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--C(NR¹⁷)--N(R⁵)R⁶, --C(R⁷)H--O--N(R⁵)R⁶, heterocyclyl (wherein the heterocyclyl radical is not attached to the radical of formula (i) through a nitrogen atom and is optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (wherein the heterocyclyl radical is not attached to the alkyl radical through a nitrogen atom and is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

each R⁴ is independently hydrogen, alkyl, halo, haloalkyl, cyano, nitro, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, or --R⁸ --N(R⁵)R⁶ ;

R⁵ and R⁶ are each independently hydrogen, alkyl, aryl or aralkyl;

each R⁷ is independently hydrogen or alkyl;

each R⁸ is independently a straight or branched alkylene, alkylidene or alkylidyne chain;

each R⁹ is independently alkyl, aryl or aralkyl;

R¹⁰ and R¹¹ are each independently hydrogen, alkyl, haloalkyl, aryl, aralkyl, formyl, cyano, --R⁸ --CN, --OR⁵, --R⁸ --OR⁵, --S(O)_p --R¹⁵ (where p is 0 to

     2), --R⁸ --S(O)_p --R¹⁵ (where p is 0 to

     2), --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --C(O)--R¹⁵, --C(O)NH₂, --R⁸ --C(O)NH₂, --C(S)NH₂, --C(O)--S--R⁵, --C(O)--N(R⁵)R¹⁵, --R⁸ --C(O)--N(R⁵)R¹⁵, --C(S)--N(R⁵)R¹⁵, --R⁸ --N(R⁵)--C(O)H, --R⁸ --N(R⁵)--C(O)R¹⁵, --C(O)O--R⁸ --N(R⁵)R⁶, --C(N(R⁵)R⁶)=C(R¹⁸)R¹⁰, --R⁸ --N(R⁵)-P(O)(OR⁵)₂, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R9 (where p is 0 to

     2), --R --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, oxo, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --S(O)_p --R⁹ (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

or R¹⁰ and R¹¹ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, halo, haloalkyl, aryl, aralkyl, oxo, nitro, cyano, --R⁸ --CN, =N(R¹⁷), --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)N(R⁵)R⁶, --R⁸ --C(O)N(R⁵)R⁶, --N(R⁵)--N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), --S(O)p--R9 (where p is 0 to

     2), --R⁸ --S(O)_p --R⁹ (where p is 0 to

     2), --(R⁸ -O)_t --R⁵ (where t is I to

     6), and heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶);

R¹² is a side chain of an α

-amino acid;

each R¹⁵ is independently alkyl, cycloalkyl, haloalkyl, aryl, aralkyl, --R⁸ --O--C(O)--R⁵, --R⁸ --OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, heterocyclyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶, and --C(O)N(R⁵)R⁶);

or R⁵ and R¹⁵ together with the nitrogen to which they are attached form a N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, amino, monoalkylamino, dialkylamino, --OR⁵, --C(O)OR⁵, aminocarbonyl, monoalkylaminocarbonyl, and dialkylaminocarbonyl;

each R¹⁶ is independently alkyl, aryl, aralkyl, --R⁸ --OR⁵, --R⁸ --N(R⁵)R⁶, cycloalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, halo and --OR⁵), heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

or

both R^16'"'"' s together with the nitrogen to which they are attached (and wherein the R⁹ substituent is not present) form an aromatic N-heterocyclic ring containing zero to three additional hetero atoms, where the N-heterocyclic ring is optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --N(R⁵)R⁶, --R⁸ --N(R⁵)R⁶, --C(O)R⁵, --C(O)--(R⁸ --O)_t --R⁵ (where t is 1 to

     6), and --(R⁸ --O)_t --R⁵ (where t is 1 to

     6);

each R¹⁷ is independently hydrogen, alkyl, aryl, aralkyl, cyano, --OR⁵, --R⁸ --OR⁵, --C(O)OR⁵, --R⁸ --C(O)OR⁵, --C(O)--N(R⁵)R⁶, or --R⁸ --C(O)--N(R⁵)R⁶ ;

R¹⁸ is hydrogen, alkyl, aryl, aralkyl, cyano, --C(O)OR⁶, or --NO₂ ; and

each R¹⁹ is cycloalkyl, haloalkyl, --R⁸ --OR⁵, --R⁸ --N(R⁵)R⁶, --R⁸ --C(O)OR⁵, --R⁸ --C(O)N(R⁵)R⁶, heterocyclyl (optionally substituted by alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ or --C(O)N(R⁵)R⁶), or heterocyclylalkyl (optionally substituted by one or more substituents selected from the group consisting of alkyl, aryl, aralkyl, halo, haloalkyl, --OR⁵, --C(O)OR⁵, --N(R⁵)R⁶ and --C(O)N(R⁵)R⁶);

as a single stereoisomer or a mixture thereof;

or a pharmaceutically acceptable salt thereof.