Quinolinones and uses thereof

• US 6,713,462 B2
• Filed: 06/21/2002
• Issued: 03/30/2004
• Est. Priority Date: 06/21/2001
• Status: Expired due to Term

• Current Assignee: Takeda Pharmaceutical Company Limited
• Original Assignee: Ariad Pharmaceuticals Incorporated (Takeda Pharmaceutical Company Limited)
• Inventors: Sawyer, Tomi K., Shakespeare, William C., Wang, Yihan, Metcalf, Chester A. III, Sundaramoorthi, Rajeswari, Bohacek, Regine
• Primary Examiner(s): SEAMAN, D MARGARET M
• Application Number:
  US10/177,500
• Publication Number:
  US 20030114486A1
• Time in Patent Office: 648 Days
• Field of Search: 514/82, 514/312, 546/23, 546/153, 546/155, 546/157, 546/158
• US Class Current: 514/82
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07F 9/4012 substituted by B, Si, P or a metal C07F9/4025 takes precedence
• CPC Class Codes: C07F 9/58 Pyridine rings
• CPC Class Codes: C07F 9/60 Quinoline or hydrogenated quinoline ring systems
• CPC Class Codes: C07F 9/65583 each of the hetero rings containing nitrogen as ring hetero atom

Abstract

The invention relates to compounds of the general formula (and pharmaceutically acceptable derivatives thereof):

in which R^A, R^B, R^C, R^D, R⁵, R⁷, R⁹, R^9a, AK, p, q, r and X are as defined herein, and to their preparation and use.

Claims

1. A compound having the structure (and pharmaceutically acceptable derivatives thereof):

wherein the dotted line represents an optional bond;

X is O, S or NR^H;

R^A is hydrogen, oxygen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^B is an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, 13 CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^D is an aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

at least one of R^B or R^D as defined above, comprises a phosphorus-containing moiety.

2. The compound of claim 1, wherein if q is 0;

and R^B comprises the only phosphorus-containing moiety PCM and PCM is —

P(═

O)OR′

R″

, or if R^9a is —

C_1-6alkylP(═

O)OR′

OR″

;

wherein R′ and

R″

are independently hydrogen, C_1-6alkyl, —

(CR_xR_y)_ω

—

C_3-10cycloalkyl or arylC_1-6alkyl;

wherein w is an integer from 0-5 and R_x and R_y are independently hydrogen or C_1-6alkyl;

then R^B is not phenyl.

3. The compound of claim 1, wherein if q is 0;

and R^B and R^D are each phenyl, then neither R^B nor R^D is substituted with —

P(═

O)OR′

R″

; and

R^9a is not —

C_1-6alkylP(═

O)OR′

OR″

;

wherein R′ and

R″

are independently hydrogen, C_1-6alkyl, —

(CR_xR_y)ω

—

C_3-10cycloalkyl or arylC_1-6alkyl;

wherein w is an integer from 0-5 and R_x and R_y are independently hydrogen or C_1-6alkyl.

4. The compound of claim 1, wherein one or more of R^B or R^D comprises or is substituted with a phosphorus-containing moiety from Series I:

wherein each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted.

5. The compound of claim 1, wherein either or both of R^B and R^D comprises or is substituted with one or more of the phosphorus-containing moieties of Series Ia or Ib:

wherein each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl, alkylaryl, or alkylheteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted; and

each occurrence of R⁴ is independently an aliphatic, heteroaliphatic, aryl or heteroaryl moiety.

6. The compound of claim 5 wherein R¹ is hydrogen or lower alkyl and M is —

CH₂—

, —

CH(OH)—

, —

CH(NH₂)—

, —

C(alkyl)(OH)—

, —

C(alkyl)(NH₂)—

, —

CH(halo)- or —

C(halo)₂-.

7. The compound of claim 1, wherein either or both of R^B or R^D comprises or is substituted with a phosphorus-containing moiety of Series Ic:

wherein each occurrence of R¹ is independently hydrogen, alkyl or aryl;

each occurrence of R⁴ is independently alkyl or aryl;

each occurrence of R⁶ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl; and

each occurrence of R⁸ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl, or a prodrug moiety.

8. The compound of claim 1, wherein either or both of R^B or R^D comprises or is substituted with a phosphorus-containing aryl or heteroaryl moieties of Series II:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂; and

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

PCM is a phosphorus-containing moiety of Series I, Series Ia, Series Ib;

or Series Ic, and m is an integer from 0-3, t is an integer from 1-3, and the sum of m+t is an integer from 1-5.

9. The compound of claim 1, wherein either or both of R^B or R^D comprises or is substituted with a phosphorus-containing aryl or heteroaryl moieties of Series IIa:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

wherein each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

m is an integer from 0-3; and

PCM is a phosphorus-containing moiety of Series I, Series Ia, Series Ib or Series Ic.

10. The compound of claim 1, wherein either or both of R^B or R^D comprises or is substituted with a phosphorus-containing aryl or heteroaryl moieties of Series IIb:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

m is an integer from 0-3.

11. The compound of claim 1, wherein either or both of R^B or R^D comprises or is substituted with a phosphorus-containing aryl or heteroaryl moieties of Series III:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN, NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x; and

m is an integer from 0-4;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

each occurrence of R⁶ is independently hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety; and

each occurrence of R⁸ is independently hydrogen, an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or a prodrug moiety;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

12. The compound of claim 4, 5, 7 or 10, wherein Y is a chemical bond linking the phosphorus atom to R¹.

13. The compound of claim 4, 5, 7 or 10, wherein Y is an oxygen atom.

14. The compound of claim 4, 5, 7 or 10, wherein Y is a chemical bond linking the phosphorus atom to R¹ and R¹ is an alkyl group having 1-6 carbon atoms.

15. The compound of claim 1, wherein R^A is hydrogen or an aliphatic or heteroaliphatic moiety.

16. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein AR is an aryl or heteroaryl moiety;

X is oxygen or sulfur;

R^A is hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^B is an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

each occurrence of n is independently 0-3;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

each occurrence of PCM is independently a phosphorus-containing moiety;

t is an integer from 1-3;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^B optionally additionally comprises a phosphorus-containing moiety.

17. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein AR is an aryl or heteroaryl moiety;

X is oxygen or sulfur;

R^A is hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^D is an aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

13 OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

13 NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

each occurrence of n is independently 0-3;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

each occurrence of PCM is independently a phosphorus-containing moiety;

t is an integer from 1-3;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^D optionally additionally comprises a phosphorus-containing moiety.

18. The compound of claim 1, wherein R^B is a phenyl moiety substituted with a phosphorus-containing moiety and the compound has the structure (and pharmaceutically acceptable derivatives thereof):

wherein each occurrence of AR is independently an aryl or heteroaryl moiety;

X is oxygen or sulfur;

R^A is hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

each occurrence of n is independently 0-3;

q is an integer from 0 -5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

PCM, for each occurrence, is independently a phosphorus-containing moiety;

t and t′

are each independently an integer from 0-3;

wherein the sum t+t′

is at least 1;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

19. The compound of claim 16, 17 or 18, wherein AR is an aryl or heteroaryl moiety selected from phenyl, pyridyl, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, pyrazole and pyrimidine, optionally further substituted with one or more occurrences of R³ as defined above.

20. The compound of claim 19 wherein each occurrence of R³ is independently hydrogen, halogen, cyano, hydroxy, or alkoxy.

21. The compound of claim 1, wherein R^B is a phenyl moiety substituted with a phosphorus-containing moiety and the compound has the structure (and pharmaceutically acceptable derivatives thereof):

X is oxygen or sulfur;

R^A is hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^B is an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

each occurrence of n is independently 0-3;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

each occurrence of R³ is independently hydrogen;

halogen;

R¹;

—

GR¹;

—

CO(Y′

R¹);

acylamino, amido, amidino, cyano, nitro, azido, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, or sulfonamido;

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits; and

each occurrence of x is independently an integer from 0-6;

s is an integer from 0-3;

each occurrence of PCM is independently a phosphorus-containing moiety;

t is an integer from 1-3;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^B optionally additionally comprises a phosphorus-containing moiety.

22. The compound of claim 1, wherein R^B is a phenyl moiety substituted with a phosphorus-containing moiety and the compound has the structure (and pharmaceutically acceptable derivatives thereof):

wherein X is oxygen or sulfur;

R^A is hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

each occurrence of n is independently 0-3;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

each occurrence of R³ is independently hydrogen;

halogen;

R¹;

—

GR¹;

—

CO(Y′

R¹);

acylamino, amido, amidino, cyano, nitro, azido, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, or sulfonamido;

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits; and

each occurrence of x is independently an integer from 0-6;

s is an integer from 0-3;

PCM is a phosphorus-containing moiety;

t is an integer from 1-3;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^D optionally additionally comprises a phosphorus-containing moiety.

23. The compound of claim 1, wherein R^B is a phenyl moiety substituted with a phosphorus-containing moiety and the compound has the structure (and pharmaceutically acceptable derivatives thereof):

wherein X is oxygen or sulfur;

R^A is hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

13 (CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

each occurrence of n is independently 0-3;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

each occurrence of R³ is independently hydrogen;

halogen;

R¹;

—

GR¹;

—

CO(Y′

R¹);

acylamino, amido, amidino, cyano, nitro, azido, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, or sulfonamido;

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits; and

each occurrence of x is independently an integer from 0-6;

each occurrence of s is independently an integer from 0-3;

each occurrence of PCM is independently a phosphorus-containing moiety;

t and t′

are each independently an integer from 0-3;

wherein the sum t+t′

is at least 1;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

24. The compound of any one of claims 16-23, wherein R^9a is an aliphatic or heteroaliphatic moiety.

25. The compound of any one of claims 16-23, wherein R^9a is a C_1-6 alkyl or heteroalkyl moiety.

26. The compound of any one of claims 16-23, wherein R^9a is hydrogen, methyl or ethyl.

27. The compound of any one of claims 16-23, wherein R⁷ is NH₂ or N(alkyl)₂.

28. The compound of claim 1, wherein X is O, R⁷ is NH₂ and the compound has the structure (and pharmaceutically acceptable derivatives thereof):

wherein is hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^B is an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^C is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

halogen;

cyano;

alkyloxycarbonyl;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, and wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R^D is an aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R<sup>M, —

CH≡

NORJ</sup>, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

R⁷ is hydrogen;

aliphatic;

heteroaliphatic;

aryl;

heteroaryl;

cyano;

—

C(O)R^J;

—

C(O)OR^J;

—

NR^JC(O)OR^K;

—

OC(O)R^J;

—

NR^JSO₂R^K;

—

SO₂NR^JR^K;

—

NR^JC(O)R^K;

—

C(O)NR^JR^K;

—

CH═

NOR^J;

—

S(O)_nR^J, wherein n is an integer from 0 to 2;

—

(CR^LCR^M)_u—

C≡

CR^J;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

CO(NOR^L)R^M, —

CH═

NOR^J, —

NR^LR^M, —

S(O)₂R^L, —

P(O)(OR^L)R^M, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

u is an integer from 0-6;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an aliphatic moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an aliphatic or heteroaliphatic moiety;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

at least one of R^B or R^D as defined above, comprises a phosphorus-containing moiety.

29. The compound of any one of claims 16-18, 21-23 and 28 wherein either or both of R^B or R^D or AR or phenyl group when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series I:

wherein each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)^x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

each occurrence of M^Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted.

30. The compound of any one of claims 16-18, 21-23 and 28, wherein either or both of R^B or PR^D or AR or phenyl group when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series Ia or Ib:

wherein each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl, alkylaryl, or alkylheteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted; and

each occurrence of R⁴ is independently an aliphatic, heteroaliphatic, aryl or heteroaryl moiety.

31. The compound of any one of claims 16-18, 21-23 and 28, wherein either or both of R^B or R^D or AR or phenyl group when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series Ic:

wherein each occurrence of R¹ is independently hydrogen, alkyl or aryl;

each occurrence of R⁴ is independently alkyl or aryl;

each occurrence of R⁶ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl; and

each occurrence of R⁸ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl, or a prodrug moiety.

32. The compound of any one of claims 16-18, 21-23 and 28, wherein either or both of R^B or R^D or AR or phenyl group when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series II:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂; and

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

PCM is a phosphorus-containing moiety of Series I, Series Ia, Series Ib;

or Series Ic, and m is an integer from 0-3, t is an integer from 1-3, and the sum of m+t is an integer from 1-5.

33. The compound of any one of claims 16-18, 21-23 and 28, wherein either or both of R^B or R^D or AR or phenyl group when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series IIa:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR<sup>1(Y′

R1</sup>);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

wherein each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

m is an integer from 0-3; and

PCM is a phosphorus-containing moiety of Series I, Series Ia, Series Ib or Series Ic.

34. The compound of claim 33, wherein PCM is a phosphorus-containing moiety of Series Ic:

wherein each occurrence of R¹ is independently hydrogen, alkyl or aryl;

each occurrence of R⁴ is independently alkyl or aryl;

each occurrence of R⁶ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl; and

each occurrence of R⁸ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl, or a prodrug moiety.

35. The compound of any one of claims 16-18, 21-23 and 28, wherein either or both of R^B or R^D or AR or phenyl group when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series IIb:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

S₂(YR¹) or —

C(O)(YR¹);

each occurrence of Y is independently —

O—

, —

SO—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

m is an integer from 0-3.

36. The compound of any one of claims 16-18, 21-23 and 28, wherein either or both of R^B or R^D or AR or phenyl group when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series III:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of G is independently absent, or is —

O—

—

S—

, —

NR¹—

, S(O)₂, or (M)_x; and

m is an integer from 0-4;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

each occurrence of R⁶ is independently hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety; and

each occurrence of R⁸ is independently hydrogen, an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or a prodrug moiety;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

37. The compound of any one of claims 16-18, 21-23 and 28, wherein both R^B and R^D or AR or phenyl group when R^B and/or R^D are defined as such, independently comprises or is substituted with a phosphorus-containing moiety of Series I, Ia, Ib, Ic, II, IIa or IIb.

38. The compound of any one of claims 16-18, 21-23 and 28, wherein both R^B and R^D or AR or phenyl group when R^B and/or R^D are defined as such, independently comprises or is substituted with a phosphorus-containing moiety of Series Ic:

wherein each occurrence of R¹ is independently hydrogen, alkyl or aryl;

each occurrence of R⁴ is independently alkyl or aryl;

each occurrence of R⁶ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl; and

each occurrence of R⁸ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl, or a prodrug moiety.

39. The compound of any one of claims 16-18, 21-23 and 28, wherein Y is a chemical bond linking the phosphorus atom to R¹.

40. The compound of any one of claims 16-18, 21-23 and 28, wherein Y is an oxygen atom.

41. The compound of any one of claims 16-18, 21-23 and 28, wherein Y is a chemical bond linking the phosphorus atom to R¹ and R¹ is an alkyl group having 1-6 carbon atoms.

42. The compound of any one of claims 16-18, 21-23 and 28, wherein R^A is hydrogen or an aliphatic or heteroaliphatic moiety.

43. The compound of any one of claims 16-18, 21-23 and 28, wherein M is —

CR_xR_y, wherein each occurrence of R_x and R_y is independently hydrogen, halogen, alkyl, heteroalkyl, OR^L or NR^LR^M;

wherein each occurrence of R^L and R^M is independently hydrogen, or an alkyl, heteroalkyl, aryl or heteroaryl moiety.

44. The compound of claim 43, wherein x is 1 and M is —

CH₂—

, —

CH(OH)—

, —

CH(NH₂)—

, —

C(alkyl)(OH)—

, —

C(alkyl)(NH₂)—

, —

CH(halo)- or —

C(halo)₂-.

45. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein AR is an aryl or heteroaryl moiety;

R^A is hydrogen, oxygen, or an alkyl or heteroalkyl moiety;

R^B is an alkyl, heteroalkyl, aryl or heteroaryl moiety;

R^C is hydrogen;

halogen, cyano or an alkyl or heteroalkyl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen, halogen, alkyl or heteroalkyl;

R⁷ is hydrogen;

alkyl;

heteroalkyl;

aryl;

heteroaryl;

cyano;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

NR^LR^M, or an alkyl, heteroalkyl, aryl or heteroaryl moiety; and

wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an alkyl or heteroalkyl moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an alkyl or heteroalkyl moiety;

K is O or S;

each occurrence of Y is independently —

O—

, —

S—

, NR¹—

, or a chemical bond linking R¹ to P,

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is 0-6;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^B optionally additionally comprises or is substituted with a phosphorus-containing moiety.

46. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein AR is an aryl or heteroaryl moiety;

R^A is hydrogen, oxygen, or an alkyl or heteroalkyl moiety;

R^C is hydrogen;

halogen, cyano or an alkyl or heteroalkyl moiety;

R^D is an alkyl, heteroalkyl, aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen, halogen, alkyl or heteroalkyl;

R⁷ is hydrogen;

alkyl;

heteroalkyl;

aryl;

heteroaryl;

cyano;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

NR^LR^M, or an alkyl, heteroalkyl, aryl or heteroaryl moiety; and

wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an alkyl or heteroalkyl moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an alkyl or heteroalkyl moiety;

K is O or S;

each occurrence of Y is independently —

O—

, —

S—

, NR¹—

, or a chemical bond linking R¹ to P,

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is 0-6;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^D optionally additionally comprises or is substituted with a phosphorus-containing moiety.

47. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein each occurrence of AR is independently an aryl or heteroaryl moiety;

R^A is hydrogen, oxygen, or an alkyl or heteroalkyl moiety;

R^C is hydrogen;

halogen, cyano or an alkyl or heteroalkyl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen, halogen, alkyl or heteroalkyl;

R⁷ is hydrogen;

alkyl;

heteroalkyl;

aryl;

heteroaryl;

cyano;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

NR^LR^M, or an alkyl, heteroalkyl, aryl or heteroaryl moiety;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an alkyl or heteroalkyl moiety; and

wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an alkyl or heteroalkyl moiety;

K is O or S;

each occurrence of Y is independently —

O—

, —

S—

, NR¹—

, or a chemical bond linking R¹ to P,

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is 0-6;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

48. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is hydrogen, oxygen, or an alkyl or heteroalkyl moiety;

R^B is an alkyl, heteroalkyl, aryl or heteroaryl moiety;

R^C is hydrogen;

halogen, cyano or an alkyl or heteroalkyl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen, halogen, alkyl or heteroalkyl;

R⁷ is hydrogen;

alkyl;

heteroalkyl;

aryl;

heteroaryl;

cyano;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

NR^LR^M, or an alkyl, heteroalkyl, aryl or heteroaryl moiety; and

wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an alkyl or heteroalkyl moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an alkyl or heteroalkyl moiety;

K is 0 or S;

each occurrence of Y is independently —

O—

, —

S—

, NR¹—

, or a chemical bond linking R¹ to P,

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is 0-6;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^B optionally additionally comprises or is substituted with a phosphorus-containing moiety.

49. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is hydrogen, oxygen, or an alkyl or heteroalkyl moiety;

R^C is hydrogen;

halogen, cyano or an alkyl or heteroalkyl moiety;

R^D is an alkyl, heteroalkyl, aryl or heteroaryl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen, halogen, alkyl or heteroalkyl;

R⁷ is hydrogen;

alkyl;

heteroalkyl;

aryl;

heteroaryl;

cyano;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

NR^LR^M, or an alkyl, heteroalkyl, aryl or heteroaryl moiety; and

wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an alkyl or heteroalkyl moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an alkyl or heteroalkyl moiety;

K is O or S;

each occurrence of Y is independently —

O—

, —

S—

, NR¹—

, or a chemical bond linking R¹ to P,

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is 0-6;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted; and

R^D optionally additionally comprises or is substituted with a phosphorus-containing moiety.

50. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is hydrogen, oxygen, or an alkyl or heteroalkyl moiety;

R^C is hydrogen;

halogen, cyano or an alkyl or heteroalkyl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen, halogen, alkyl or heteroalkyl;

R⁷ is hydrogen;

alkyl;

heteroalkyl;

aryl;

heteroaryl;

cyano;

or —

ZR^J, wherein each occurrence of Z is independently —

O—

, —

S—

, NR^K, —

C(O)—

, —

S(O)₂—

, or —

COO—

, wherein each occurrence of R^J and R^K is independently hydrogen, COR^L, COOR^L, CONR^LR^M, —

NR^LR^M, or an alkyl, heteroalkyl, aryl or heteroaryl moiety; and

wherein each occurrence of R^L and R^M is independently hydrogen, or an aliphatic, heteroaliphatic, aryl or heteroaryl moiety;

AK is (CR^PCR^Q);

each occurrence of R^P and R^Q is independently hydrogen or an alkyl or heteroalkyl moiety;

q is an integer from 0 to 5;

p is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an alkyl or heteroalkyl moiety;

K is O or S;

each occurrence of Y is independently —

O—

, —

S—

, NR¹—

, or a chemical bond linking R¹ to P,

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is 0-6;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

51. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is hydrogen, oxygen, or an alkyl or heteroalkyl moiety;

R^B is an alkyl, heteroalkyl, aryl or heteroaryl moiety;

R^C is hydrogen;

halogen, cyano or an alkyl or heteroalkyl moiety;

each occurrence of R⁹ and R⁵ is independently hydrogen, halogen, alkyl or heteroalkyl;

is an integer from 0-3;

r is an integer from 0-2;

R^9a is hydrogen;

or an alkyl or heteroalkyl moiety;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;

and wherein either one or both of R^B and R^D comprises or is substituted with a phosphorus-containing moiety of Series II;

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR<sup>1;

—

CO(Y′

R1</sup>);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂; and

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

PCM is a phosphorus-containing moiety of Series I, Series Ia, Series Ib;

or Series Ic, and m is an integer from 0-3, t is an integer from 1-3, and the sum of m+t is an integer from 1-5.

52. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is hydrogen, oxygen or an aliphatic or heteroaliphatic moiety;

R^B is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;

R^D is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;

wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted;

and wherein either one or both of R^B and R^D comprises or is substituted with a phosphorus containing moiety of Series II;

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂; and

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

PCM is a phosphorus-containing moiety of Series I, Series Ia, Series Ib;

or Series Ic, and m is an integer from 0-3, t is an integer from 1-3, and the sum of m+t is an integer from 1-5.

53. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is an aliphatic or heteroaliphatic moiety;

R^B is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;

R³ independently represents from 0-3 substituents selected from hydrogen;

halogen;

R¹;

—

GR¹;

—

CO(Y′

R¹);

acylamino, amido, amidino, cyano, nitro, azido, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, and sulfonamido;

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

t is an integer from 1-3;

s is an integer from 0-4;

wherein the sum t+s is 1-5; and

wherein PCM is a phosphorus-containing moiety selected from Series I;

wherein each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted.

54. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is an aliphatic or heteroaliphatic moiety;

R^D is an aryl, heteroaryl, alkylaryl, or alkylheteroaryl moiety;

R³ independently represents from 0-3 substituents selected from hydrogen;

halogen;

R¹;

—

GR¹;

—

CO(Y′

R¹);

acylamino, amido, amidino, cyano, nitro, azido, sulfonyl, sulfoxido, sulfate, sulfonate, sulfamoyl, and sulfonamido;

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

t is an integer from 1-3;

s is an integer from 0-3, wherein the sum t+s is 1-5; and

wherein PCM is a phosphorus-containing moiety selected from Series I;

wherein each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted.

55. The compound of claim 51, 52, 53 or 54, wherein either or both of R^B or R^D, or phenyl when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series IIa:

wherein wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

wherein each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

m is an integer from 0-3; and

PCM is a phosphorus-containing moiety of Series I, Series Ia, Series Ib or Series Ic.

56. The compound of claim 55, wherein PCM is a phosphorus-containing moiety of Series Ic:

wherein each occurrence of R¹ is independently hydrogen, alkyl or aryl;

each occurrence of R⁴ is independently alkyl or aryl;

each occurrence of R⁶ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl; and

each occurrence of R⁸ is independently hydrogen, alkyl, heteroalkyl, aryl or heteroaryl, or a prodrug moiety.

57. The compound of claim 51, 52, 53 or 54, wherein either or both of R^B or R^D, or phenyl when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series IIb:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of R² is independently R¹, —

PK(YR¹)(YR¹), —

SO₂(YR¹) or —

C(O)(YR¹);

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x;

each occurrence of M_Y is independently a methine group or a lower alkyl moiety which contains a methine group and optionally may be further substituted;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6; and

m is an integer from 0-3.

58. The compound of claim 51, 52, 53 or 54, wherein either or both of R^B or R^D, or phenyl when R^B and/or R^D are defined as such, comprises or is substituted with a phosphorus-containing moiety of Series III:

wherein each occurrence of R³ is independently hydrogen;

halogen;

—

CN;

NO₂;

N₃;

R¹;

—

GR¹;

—

CO(Y′

R¹);

—

NR¹(Y′

R¹);

S(O)₂(Y′

R¹);

wherein each occurrence of Y′

is independently —

O—

, —

S—

, —

NR¹—

, —

C(O)—

, —

COO—

or S(O)₂;

each occurrence of G is independently absent, or is —

O—

, —

S—

, —

NR¹—

, S(O)₂, or (M)_x; and

m is an integer from 0-4;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

each occurrence of x is independently an integer from 0-6;

each occurrence of R⁶ is independently hydrogen, aliphatic, heteroaliphatic, aryl or heteroaryl moiety; and

each occurrence of R⁸ is independently hydrogen, an aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or a prodrug moiety;

wherein in each of the foregoing groups each aliphatic or heteroaliphatic moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

59. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is an aliphatic or heteroaliphatic moiety;

each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹ —

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is an integer from 0-6;

each occurrence of R³ independently represents hydrogen;

halogen;

C_1-6 alkyl; and

C_1-6 alkyloxy;

each occurrence of s is independently an integer from 0-3; and

wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

60. The compound of claim 1, having the structure (and pharmaceutically acceptable derivatives thereof):

wherein R^A is an aliphatic or heteroaliphatic moiety;

each occurrence of K is independently O or S;

each occurrence of Y is independently —

O—

, —

S—

, —

NH—

, —

NR¹—

, or a chemical bond linking R¹ to P;

each occurrence of R¹ is independently a substituted or unsubstituted aliphatic, heteroaliphatic, aryl or heteroaryl moiety, or, except in YR¹ moieties in which Y is a covalent bond, R¹ may also be H;

each occurrence of M is independently a substituted or unsubstituted C₁-alkylene moiety, and any two adjacent M moieties may be connected with a single, double or triple bond, as valency permits;

x is an integer from 0-6;

each occurrence of R³ independently represents hydrogen;

halogen;

C_1-6 alkyl; and

C_1-6 alkyloxy;

each occurrence of s is independently an integer from 0-3; and

wherein in each of the foregoing groups each aliphatic, heteroaliphatic, alkylaryl, or alkylheteroaryl moiety may be branched or unbranched, cyclic or acyclic and substituted or unsubstituted, and may contain one or more electronically unsaturated bonds, and each aryl and heteroaryl moiety may be substituted or unsubstituted.

61. The compound of any one of claims 45-54 and 59-60 wherein Y is a chemical bond linking the phosphorus atom to R¹.

62. The compound of any one of claims 45-54 and 59-60 wherein Y is an oxygen atom.

63. The compound of any one of claims 45-54 and 59-60 wherein Y is a chemical bond linking the phosphorus atom to R¹ and R¹ is an alkyl group having 1-6 carbon atoms.

64. The compound of any one of claims 45-54 and 59-60 wherein R^A is hydrogen or an aliphatic or heteroaliphatic moiety.

65. The compound of any one of claims 45-54 and 59-60 wherein K is oxygen.

66. The compound of any one of claims 45-54 and 59-60 wherein x is 0.

67. The compound of any one of claims 45-54 and 59-60 wherein x is 1-4 and M is —

CH₂—

.

68. A pharmaceutical composition comprising a compound of any one of claims 1, 16-18, 21-23, 28, 45-54 and 59-60, or a pharmaceutically acceptable derivative thereof;

and

a pharmaceutically acceptable carrier or diluent,

said composition optionally further comprising an additional therapeutic agent.

69. The composition of claim 68, wherein the composition further comprises an additional therapeutic agent and the therapeutic agent is an anticancer agent, an antiproliferative agent, an approved agent for the treatment of osteoporosis, or an approved agent for the treatment of disorders related to increased vascular permeability.

70. A method for treating a bone-related disorder comprising administering a therapeutically effective amount of a compound of any one of claims 1, 16-18, 21-23, 28, 45-54 and 59-60, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof, and optionally further comprising administering an additional therapeutic agent.

71. A method for treating a proliferative disorder comprising administering a therapeutically effective amount of a compound of any one of claims 1, 16-18, 21-23, 28, 45-54 and 59-60, or a pharmaceutically acceptable derivative thereof, to a subject in need thereof, and optionally further comprising administering an additional therapeutic agent.

72. The method of claim 71, wherein the proliferative disorder is cancer.

73. The method of claim 71, wherein the method further comprises administering a cytotoxic agent to a subject.

74. The method of claim 73, wherein the cytotoxic agent is an anticancer agent.

75. A method for the treatment and prophylaxis of diseases which are mediated by a kinase inhibited by a compound of any one of claims 1, 16-18, 21-23, 28, 45-54 and 59-60, comprising

administering a therapeutically effective amound of any one of the compounds , or a pharmaceutically acceptable derivative thereof, to a subject in need thereof.