Pyrrole Derivatives As Pharmaceutical Agents

• US 20080234270A1
• Filed: 07/30/2005
• Published: 09/25/2008
• Est. Priority Date: 07/30/2004
• Status: Active Grant

• Current Assignee: Exelixis Incorporated
• Original Assignee: Exelixis Incorporated
• Inventors: Wang, Yong, Forsyth, Timothy Patrick, Martin, Richard, Mac, Morrison B., Murphy, Brett, Flatt, Brenton T., Mohan, Raju, Mann, Grace, Chen, Jeff, Mann, Larry W., Gu, Xiao-Hui, Wang, Tie-Lin, Nyman, Michael Charles, Canne Bannen, Lynne, Wu, Jason H., Dalrymple, Lisa Esther, Stevens, William C.
• Granted Patent: US 8,026,237 B2
• Time in Patent Office: Days
• US Class Current: 514/235.5
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/42 for decreasing, blocking or antagonising the activity of mineralocorticosteroids
• CPC Class Codes: A61P 5/44 Glucocorticosteroids; Drugs increasing or potentiating the activity of glucocorticosteroids
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: C07D 207/416 : with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to other ring carbon atoms
• CPC Class Codes: C07D 401/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 : linked by a chain containing hetero atoms as chain links

Abstract

Compounds, compositions and methods for modulating the activity of receptors are provided. In particular compounds and compositions are provided for modulating the activity of receptors and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder directly or indirectly related to the activity of the receptors.

Claims

1-65. -65. (canceled)

66. The compound of formula (III);

67. The compound of claim 66 wherein:

R⁵ is cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl, where each is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, alkoxy, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —

R⁸—

OR⁹, —

R⁸—

SR⁹, —

R⁸—

S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

N(R⁹)₂, —

R⁸—

CN, —

R⁸—

C(O)R⁹, —

R⁸—

C(S)R⁹, —

R⁸—

C(NR⁹)R⁹, —

R⁸—

C(O)OR⁹, —

R⁸—

C(S)OR⁹, —

R⁸—

C(NR⁹)OR⁹, —

R⁸—

C(O)N(R⁹)₂, —

R⁸—

C(S)N(R⁹)₂, —

R⁸—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)SR⁹, —

R⁸—

C(S)SR⁹, —

R⁸—

C(NR⁹)SR⁹, —

R⁸—

S(O)_tOR⁹ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N═

C(R⁹)₂, —

R⁸—

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

N(R⁹)C(O)R¹⁰, —

R⁸—

N(R⁹)C(O)OR¹⁰, —

R⁸—

N(R⁹)C(O)SR¹⁰, —

R⁸—

N(R⁹)C(NR⁹)SR¹⁰, —

R⁸—

N(R⁹)C(S)SR¹⁰, —

R⁸—

N(R⁹)C(O)N(R⁹)₂, —

R⁸—

N(R⁹)C(NR⁹)N(R⁹)₂, —

R⁸—

N(R⁹)C(S)N(R⁹)₂, —

R⁸—

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

OC(O)R¹⁰, —

R⁸—

OC(NR⁹)R¹⁰, —

R⁸—

OC(S)R¹⁰, —

R⁸—

OC(O)OR¹⁰, —

R⁸—

OC(NR⁹)OR¹⁰, —

R⁸—

OC(S)OR¹⁰, —

R⁸—

OC(O)SR⁹, —

R⁸—

OC(O)N(R⁹)₂, —

R⁸—

OC(NR⁹)N(R⁹)₂, —

R⁸—

OC(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)R⁹, —

R⁸—

C(O)—

R¹¹—

C(S)R⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)R⁹, —

R⁸—

C(O)—

R¹¹—

C(O)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(O)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)SR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)SR⁹ and —

R⁸—

C(O)—

R¹¹—

C(NR⁹)SR⁹;

68. The compound of claim 66

wherein:

R¹ is cyano, halo, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl;

R³ is hydrogen or halo;

R⁴ is aryl or heteroaryl, where each is optionally substituted by one or more substituents selected from the group consisting of halo, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —

R⁸—

OR⁹, —

R⁸—

SR⁹, —

R⁸—

S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

N(R⁹)₂, —

R⁸—

CN, —

R⁸—

C(O)R⁹, —

R⁸—

C(S)R⁹, —

R⁸—

C(NR⁹)R⁹, —

R⁸—

C(O)OR⁹, —

R⁸—

C(S)OR⁹, —

R⁸—

C(NR⁹)OR⁹, —

R⁸—

C(O)N(R⁹)₂, —

R⁸—

C(S)N(R⁹)₂, —

R⁸—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)SR⁹, —

R⁸—

C(S)SR⁹, —

R⁸—

C(NR⁹)SR⁹, —

R⁸—

S(O)_tOR⁹ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N═

C(R⁹)₂, —

R⁸—

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

N(R⁹)C(O)R¹⁰, —

R⁸—

N(R⁹)C(O)OR¹⁰, —

R⁸—

N(R⁹)C(O)SR¹⁰, —

R⁸—

N(R⁹)C(NR⁹)SR¹⁰, —

R⁸—

N(R⁹)C(S)SR¹⁰, —

R⁸—

N(R⁹)C(O)N(R⁹)₂, —

R⁸—

N(R⁹)C(NR⁹)N(R⁹)₂, —

R⁸—

N(R⁹)C(S)N(R⁹)₂, —

R⁸—

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

OC(O)R¹⁰, —

R⁸—

OC(NR⁹)R¹⁰, —

R⁸—

OC(S)R¹⁰, —

R⁸—

OC(O)OR¹⁰, —

R⁸—

OC(NR⁹)OR¹⁰, —

R⁸—

OC(S)OR¹⁰, —

R⁸—

OC(O)SR⁹, —

R⁸—

OC(O)N(R⁹)₂, —

R⁸—

OC(NR⁹)N(R⁹)₂, —

R⁸—

OC(S)N(R⁹)₂;

—

R⁸—

C(O)—

R¹¹—

C(O)R¹⁴, —

R⁸—

C(O)—

R¹¹—

C(S)R¹⁴, —

R⁸—

C(O)—

R¹¹—

C(NR¹⁴)R¹⁴, —

R⁸—

C(O)—

R¹¹—

C(O)OR¹⁴, —

R⁸—

C(O)—

R¹¹—

C(S)OR¹⁴, —

R⁸—

C(O)—

R¹¹—

C(NR¹⁴)OR¹⁴, —

R⁸—

C(O)—

R¹¹—

C(O)N(R¹⁴)₂, —

R⁸—

C(O)—

R¹¹—

C(S)N(R¹⁴)₂, —

R⁸—

C(O)—

R¹¹—

C(NR¹⁴)N(R¹⁴)₂, —

R⁸—

C(O)—

R¹¹—

C(O)SR¹⁴, —

R⁸—

C(O)—

R¹¹—

C(S)SR¹⁴ and —

R⁸—

C(O)—

R¹¹—

C(NR¹⁴)SR¹⁴;

R⁵ is hydrogen, —

C(O)R⁹ or —

S(O)₂R⁹;

or R⁵ is alkyl, alkenyl or alkynyl, where each is optionally substituted by one or more substituents selected from the group consisting of halo, nitro, —

OR⁹, —

SR⁹, —

S(O)_tR¹⁰ (where t is 1 or

     2), —

N(R⁹)₂, —

CN, —

C(O)R⁹, —

C(S)R⁹, —

C(NR⁹)R⁹, —

C(O)OR⁹, —

C(S)OR⁹, —

C(NR⁹)OR⁹, —

C(O)N(R⁹)₂, —

C(S)N(R⁹)₂, —

C(NR⁹)N(R⁹)₂, —

C(O)SR⁹, —

C(S)SR⁹, —

C(NR⁹)SR⁹, —

S(O)_tOR⁹ (where t is 1 or

     2), —

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

S(O)_tN(R⁹)N═

C(R⁹)₂, —

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

N(R⁹)C(O)R¹⁰, —

N(R⁹)C(O)OR¹⁰, —

N(R⁹)C(O)SR¹⁰, —

N(R⁹)C(NR⁹)SR¹⁰, —

N(R⁹)C(S)SR¹⁰, —

N(R⁹)C(O)N(R⁹)₂, —

N(R⁹)C(NR⁹)N(R⁹)₂, —

N(R⁹)C(S)N(R⁹)₂, —

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

OC(O)R¹⁰, —

OC(NR⁹)R¹⁰, —

OC(S)R¹⁰, —

OC(O)OR¹⁰, —

OC(NR⁹)OR¹⁰, —

OC(S)OR¹⁰, —

OC(O)SR⁹, —

OC(O)N(R⁹)₂, —

OC(NR⁹)N(R⁹)₂, —

OC(S)N(R⁹)₂, —

C(O)—

R¹¹—

C(O)R⁹, —

C(O)—

R¹¹—

C(S)R⁹, —

C(O)—

R¹¹—

C(NR⁹)R⁹, —

C(O)—

R¹¹—

C(O)OR⁹, —

C(O)—

R¹¹—

C(S)OR⁹, —

C(O)—

R¹¹—

C(NR⁹)OR⁹, —

C(O)—

R¹¹—

C(O)N(R⁹)₂, —

C(O)—

R¹¹—

C(S)N(R⁹)₂, —

C(O)—

R¹¹—

C(NR⁹)N(R⁹)₂, —

C(O)—

R¹¹—

C(O)SR⁹, —

C(O)—

R¹¹—

C(S)SR⁹ and —

C(O)—

R¹¹—

C(NR⁹)SR⁹;

or R⁵ is cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl or heteroaralkyl, where each is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —

R⁸—

OR⁹, —

R⁸—

SR⁹, —

R⁸—

S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

N(R⁹)₂, —

R⁸—

CN, —

R⁸—

C(O)R⁹, —

R⁸—

C(S)R⁹, —

R⁸—

C(NR⁹)R⁹, —

R⁸—

C(O)OR⁹, —

R⁸—

C(S)OR⁹, —

R⁸—

C(NR⁹)OR⁹, —

R⁸—

C(O)N(R⁹)₂, —

R⁸—

C(S)N(R⁹)₂, —

R⁸—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)SR⁹, —

R⁸—

C(S)SR⁹, —

R⁸—

C(NR⁹)SR⁹, —

R⁸—

S(O)_tOR⁹ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N═

C(R⁹)₂, —

R⁸—

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

N(R⁹)C(O)R¹⁰, —

R⁸—

N(R⁹)C(O)OR¹⁰, —

R⁸—

N(R⁹)C(O)SR¹⁰, —

R⁸—

N(R⁹)C(NR⁹)SR¹⁰, —

R⁸—

N(R⁹)C(S)SR¹⁰, —

R⁸—

N(R⁹)C(O)N(R⁹)₂, —

R⁸—

N(R⁹)C(NR⁹)N(R⁹)₂, —

R⁸—

N(R⁹)C(S)N(R⁹)₂, —

R⁸—

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

OC(O)R¹⁰, —

R⁸—

OC(NR⁹)R¹⁰, —

R⁸—

OC(S)R¹⁰, —

R⁸—

OC(O)OR¹⁰, —

R⁸—

OC(NR⁹)OR¹⁰, —

R⁸—

OC(S)OR¹⁰, —

R⁸—

OC(O)SR⁹, —

R⁸—

OC(O)N(R⁹)₂, —

R⁸—

OC(NR⁹)N(R⁹)₂, —

R⁸—

OC(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)R⁹, —

R⁸—

C(O)—

R¹¹—

C(S)R⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)R⁹, —

R⁸—

C(O)—

R¹¹—

C(O)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(O)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)SR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)SR⁹ and —

R⁸—

C(O)—

R¹¹—

C(NR⁹)SR⁹;

R⁶ is hydrogen or optionally substituted alkyl;

R⁷ is alkyl, alkenyl or alkynyl, where each is optionally substituted by one or more substituents selected from the group consisting of nitro, halo, —

OR¹⁴, —

SR¹⁴, —

S(O)_tR¹⁵ (where t is 1 or

     2), —

N(R¹⁴)₂, —

CN, —

C(O)R¹⁴, —

C(S)R¹⁴, —

C(NR¹⁴)R¹⁴, —

C(O)OR¹⁴, —

C(S)OR¹⁴, —

C(NR¹⁴)OR¹⁴, —

C(O)N(R¹⁴)₂, —

C(S)N(R¹⁴)₂, —

C(NR¹⁴)N(R¹⁴)₂, —

C(O)SR¹⁴, —

C(S)SR¹⁴, —

C(NR¹⁴)SR¹⁴, —

S(O)_tOR¹⁴ (where t is 1 or

     2), —

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2), —

S(O)_tN(R¹⁴)N(R¹⁴)₂ (where t is 1 or

     2), —

S(O)_tN(R¹⁴)N═

C(R¹⁴)₂, —

S(O)_tN(R¹⁴)C(O)R¹⁵ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R¹⁴)C(O)N(R¹⁴)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R¹⁴)C(NR¹⁴)N(R¹⁴)₂ (where t is 1 or

     2), —

N(R¹⁴)C(O)R¹⁵, —

N(R¹⁴)C(O)OR¹⁵, —

N(R¹⁴)C(O)SR¹⁵, —

N(R¹⁴)C(NR¹⁴)SR¹⁵, —

N(R¹⁴)C(S)SR¹⁵, —

N(R¹⁴)C(O)N(R¹⁴)₂, —

N(R¹⁴)C(NR¹⁴)N(R¹⁴)₂, —

N(R¹⁴)C(S)N(R¹⁴)₂, —

N(R¹⁴)S(O)_tR¹⁵ (where t is 1 or

     2), —

OC(O)R¹⁵, —

OC(NR¹⁴)R¹⁵, —

OC(S)R¹⁵, —

OC(O)OR¹⁵, —

OC(NR¹⁴)OR¹⁵, —

OC(S)OR¹⁵, —

OC(O)SR¹⁴—

OC(O)N(R¹⁴)₂, —

OC(NR¹⁴)N(R¹⁴)₂, —

OC(S)N(R¹⁴)₂, —

C(O)—

R¹⁶—

C(O)R¹⁴, —

C(O)—

R¹⁶—

C(S)R¹⁴, —

C(O)—

R¹⁶—

C(NR¹⁴)R¹⁴, —

C(O)—

R¹⁶—

C(O)OR¹⁴, C(O)—

R¹⁶—

C(S)OR¹⁴—

C(O)—

R¹⁶—

C(NR¹⁴)OR¹⁴, —

C(O)—

R¹⁶—

C(O)N(R¹⁴)₂, —

C(O)—

R¹⁶—

C(S)N(R¹⁴)₂, —

C(O)—

R¹⁶C(NR¹⁴)N(R¹⁴)₂, —

C(O)—

R¹⁶—

C(O)SR¹⁴, —

C(O)—

R¹⁶—

C(S)SR¹⁴ and —

C(O)—

R¹⁶—

C(NR¹⁴)SR¹⁴;

R⁶ is hydrogen;

R⁷ is aryl or heteroaryl, where each is optionally substituted by one or more substituents selected from the group consisting of halo, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —

R¹³—

OR¹⁴, —

R¹³—

SR¹⁴, —

R¹³—

S(O)_tR¹⁵ (where t is 1 or

     2), —

R¹³—

N(R¹⁴)₂, —

R¹³—

CN, —

R¹³—

C(O)R¹⁴, —

R¹²—

C(S)R¹⁴, —

R¹³—

C(NR¹⁴)R¹⁴, —

R¹³—

C(O)OR¹⁴, —

R¹³—

C(S)OR¹⁴, —

R¹³—

C(NR¹⁴)OR¹⁴, —

R¹³—

C(O)N(R¹⁴)₂, —

R¹³—

C(S)N(R¹⁴)₂, —

R¹³—

C(NR¹⁴)N(R¹⁴)₂, —

R¹³—

C(O)SR¹⁴, —

R¹³—

C(S)SR¹⁴, —

R¹³—

C(NR¹⁴)SR¹⁴, —

R¹³—

S(O)_tOR¹⁴ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)N(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)N═

C(R¹⁴)₂, —

R¹³—

S(O)_tN(R¹⁴)C(O)R¹⁵ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(O)N(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(NR¹⁴)N(R¹⁴)₂ (where t is 1 or

     2) and —

R¹³—

N(R¹⁴)S(O)_tR¹⁵ (where t is 1 or

     2);

where each R⁸ and R¹³ are independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where each R⁹ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl;

or

where two R⁹s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl; and

where each R¹⁴ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl andoptionally substituted heteroaralkyl;

or

where two R¹⁴s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R¹⁰ and R¹⁵ are independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and

where each R¹¹ is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain; and

as a single isomer, a mixture of isomers, or as a racemic mixture of isomers;

or as a solvate or polymorph;

or as a prodrug;

or as a pharmaceutically acceptable salt thereof.

69. The compound of claim 66 wherein R⁷ is cycloalkyl, aryl, heterocyclyl or heteroaryl, where each is substituted by R²⁶ and optionally substituted by R²⁵;

wherein;

R²⁵ is selected from the group consisting of halo, nitro, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkenyl, —

R¹³—

OR¹⁴;

—

R¹³—

SR¹⁴, —

R¹³—

S(O)_tR¹⁵ (where t is 1 or

     2), —

R¹³—

N(R¹⁴)₂, —

R¹³—

CN, —

R¹³—

C(O)R¹⁴, —

R¹³—

C(O)OR¹⁴, —

R¹³—

C(O)N(R¹⁴)₂, —

R¹³—

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(O)R¹⁵, (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(O)N(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(NR¹⁴)N(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

N(R¹⁴)C(O)R¹⁵, —

R¹³—

N(R¹⁴)S(O)_tR¹⁵ (where t is 1 or

     2), —

R¹³—

C(O)—

R¹⁶—

C(O)R¹⁴, —

R¹³—

C(O)—

R¹⁶—

C(S)R¹⁴ and —

R¹³—

C(O)—

R¹⁶—

C(O)N(R¹⁴)₂;

R²⁶ is selected from the group consisting of —

R¹³—

C(O)R¹⁴, —

R¹³—

S(O)_tR¹⁵ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2) and —

R¹³—

S(O)_tN(R¹⁴)C(O)R¹⁵ (where t is 1 or

     2);

where each R¹³ is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where each R¹⁴ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl;

or

where two R¹⁴s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R¹⁵ is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and

where each R¹⁶ is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain.

70. The compound of claim 69 wherein R⁷ is:

71. The compound of claim 70 wherein R²⁶ is in the para position.

72. The compound of claim 66 wherein R⁷ is alkyl, alkenyl or alkynyl, where each is substituted by R²⁶ and optionally substituted by R²⁵ wherein:

R²⁵ is selected from the group consisting of halo, nitro,optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —

OR¹⁴;

—

SR¹⁴, —

S(O)_tR¹⁵ (where t is 1 or

     2), —

N(R¹⁴)₂, —

CN, —

C(O)R¹⁴, —

C(O)OR¹⁴, —

C(O)N(R¹⁴)₂, —

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2), —

S(O)_tN(R¹⁴)C(O)R¹⁵, (where t is 1 or

     2), —

S(O)_tN(R¹⁴)C(O)N(R¹⁴)₂ (where t is 1 or

     2), —

S(O)_tN(R¹⁴)C(NR¹⁴)N(R¹⁴)₂ (where t is 1 or

     2), —

N(R¹⁴)C(O)R¹⁵, —

N(R¹⁴)S(O)_tR¹⁵ (where t is 1 or

     2), and —

C(O)—

R¹⁶—

R¹⁷; and

R²⁶ is selected from the group consisting of —

S(O)_tR¹⁵ (where t is 1 or

     2), —

N(R¹⁴)₂, —

C(O)R¹⁴ and —

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2);

each R¹⁴ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl;

or

where two R¹⁴s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl; and

each R¹⁵ is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl.

73. The compound of claim 66 wherein R⁷ is cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl except phenyl, aralkyl, heteroaryl or heteroaralkyl, where each is substituted by R²⁶ and optionally substituted by R²⁵ wherein:

R²⁵ is selected from the group consisting of halo, nitro, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted heteroaralkenyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heteroaryl, —

R¹³—

OR¹⁴;

—

R¹³—

SR¹⁴, —

R¹³—

S(O)_tR¹⁵ (where t is 1 or

     2), —

R¹³—

N(R¹⁴)₂, —

R¹³—

CN, —

R¹³—

C(O)R¹⁴, —

R¹³—

C(O)OR¹⁴, —

R¹³—

C(O)N(R¹⁴)₂, —

R¹³—

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(O)R¹⁵, (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(O)N(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

S(O)_tN(R¹⁴)C(NR¹⁴)N(R¹⁴)₂ (where t is 1 or

     2), —

R¹³—

N(R¹⁴)C(O)R¹⁵, —

R¹³—

N(R¹⁴)S(O)_tR¹⁵ (where t is 1 or

     2), and —

R¹³—

C(O)—

R¹⁶—

R¹⁷; and

R²⁶ is selected from the group consisting of —

S(O)_tR¹⁵ (where t is 1 or

     2), —

N(R¹⁴)₂, —

C(O)R¹⁴ and —

S(O)_tN(R¹⁴)₂ (where t is 1 or

     2);

where each R¹³ is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where each R¹⁴ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl;

or

where two R¹⁴s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl; and

where each R¹⁵ is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl.

74. The compound of claim 67 wherein R²⁵ is selected from the group consisting of halo, optionally substituted alkyl, optionally substituted cycloalkyl, —

R¹³—

OR¹⁴, —

R¹³—

SR¹⁴ and —

R¹³—

N(R¹⁴)₂;

where each R¹³ is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain; and

where each R¹⁴ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl or optionally substituted heteroaralkyl;

or

where two R¹⁴S, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl.

75. The compound of claim 67 wherein R¹ and R⁵ are each independently selected from the group consisting of cyano, optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl.

76. The compound of claim 67 wherein R¹ is hydrogen or optionally substituted alkyl and R⁵ is selected from the group consisting of optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl.

77. The compound of claim 76 wherein R⁵ is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —

R⁸—

OR⁹, —

R⁸—

SR⁹, —

R⁸—

S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

N(R⁹)₂, —

R⁸—

CN, —

R⁸—

C(O)R⁹, —

R⁸—

C(S)R⁹, —

R⁸—

C(NR⁹)R⁹, —

R⁸—

C(O)OR⁹, —

R⁸—

C(S)OR⁹, —

R⁸—

C(NR⁹)OR⁹, —

R⁸—

C(O)N(R⁹)₂, —

R⁸—

C(S)N(R⁹)₂, —

R⁸—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)SR⁹, —

R⁸—

C(S)SR⁹, —

R⁸—

C(NR⁹)SR⁹, —

R⁸—

S(O)_tOR⁹ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N═

C(R⁹)₂, —

R⁸—

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

N(R⁹)C(O)R¹⁰, —

R⁸—

N(R⁹)C(O)OR¹⁰, —

R⁸—

N(R⁹)C(O)SR¹⁰, —

R⁸—

N(R⁹)C(NR⁹)SR¹⁰, —

R⁸—

N(R⁹)C(S)SR¹⁰, —

R⁸—

N(R⁹)C(O)N(R⁹)₂, —

R⁸—

N(R⁹)C(NR⁹)N(R⁹)₂, —

R⁸—

N(R⁹)C(S)N(R⁹)₂, —

R⁸—

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

OC(O)R¹⁰, —

R⁸—

OC(NR⁹)R¹⁰, —

R⁸—

OC(S)R¹⁰, —

R⁸—

OC(O)OR¹⁰, —

R⁸—

OC(NR⁹)OR¹⁰, —

R⁸—

OC(S)OR¹⁰, —

R⁸—

OC(O)SR⁹, —

R⁸—

OC(O)N(R⁹)₂, —

R⁸—

OC(NR⁹)N(R⁹)₂, —

R⁸—

OC(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)R⁹, —

R⁸—

C(O)—

R¹¹—

C(S)R⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)R⁹, —

R⁸—

C(O)—

R¹¹—

C(O)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(O)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)SR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)SR⁹ and —

R⁸—

C(O)—

R¹¹—

C(NR⁹)SR⁹;

78. The compound of claim 75 wherein R¹ and R⁵ are each optionally substituted alkyl

79. The compound of claim 75 wherein R¹ and R⁵ are each independently alkyl or optionally substituted phenyl.

80. The compound of claim 75 wherein R⁴ is cycloalkyl, heterocyclyl, aryl or heteroaryl, where each is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —

R⁸—

OR⁹, —

R⁸—

SR⁹, —

R⁸—

S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

N(R⁹)₂, —

R⁸—

CN, —

R⁸—

C(O)R⁹, —

R⁸—

C(S)R⁹, —

R⁸—

C(NR⁹)R⁹, —

R⁸—

C(O)OR⁹, —

R⁸—

C(S)OR⁹, —

R⁸—

C(NR⁹)OR⁹, —

R⁸—

C(O)N(R⁹)₂, —

R⁸—

C(S)N(R⁹)₂, —

R⁸—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)SR⁹, —

R⁸—

C(S)SR⁹, —

R⁸—

C(NR⁹)SR⁹, —

R⁸—

S(O)_tOR⁹ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N═

C(R⁹)₂, —

R⁸—

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

N(R⁹)C(O)R¹⁰, —

R⁸—

N(R⁹)C(O)OR¹⁰, —

R⁸—

N(R⁹)C(O)SR¹⁰, —

R⁸—

N(R⁹)C(NR⁹)SR¹⁰, —

R⁸—

N(R⁹)C(S)SR¹⁰, —

R⁸—

N(R⁹)C(O)N(R⁹)₂, —

R⁸—

N(R⁹)C(NR⁹)N(R⁹)₂, —

R⁸—

N(R⁹)C(S)N(R⁹)₂, —

R⁸—

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

OC(O)R¹⁰, —

R⁸—

OC(NR⁹)R¹⁰, —

R⁸—

OC(S)R¹⁰, —

R⁸—

OC(O)OR¹⁰, —

R⁸—

OC(NR⁹)OR¹⁰, —

R⁸—

OC(S)OR¹⁰, —

R⁸—

OC(O)SR⁹, —

R⁸—

OC(O)N(R⁹)₂, —

R⁸—

OC(NR⁹)N(R⁹)₂, —

R⁸—

OC(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)R⁹, —

R⁸—

C(O)—

R¹¹—

C(S)R⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)R⁹, —

R⁸—

C(O)—

R¹¹—

C(O)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(O)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)SR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)SR⁹ and —

R⁸—

C(O)—

R¹¹—

C(NR⁹)SR⁹;

where each R⁸ is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where each R⁹ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl;

or

where two R⁹s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R¹⁰ is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and

where each R¹¹ is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain.

81. The compound of claim 80 wherein said compound is selected from the group consisting of:

5-Benzo[b]thiophen-2-yl-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(5-Acetyl-thiophen-2-yl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Benzo[1,3]dioxol-5-yl-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(1H-Indol-5-yl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Dibenzofuran-4-yl-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(1-Benzenesulfonyl-1H-indol-3-yl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-pyrimidin-5-yl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Acenaphthen-5-yl-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-(1-methyl-1H-indol-5-yl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide; and

5-(1-Benzyl-1H-pyrazol-4-yl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Biphenyl-2-yl-1-(2-diethylamino-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Biphenyl-2-yl-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-Biphenyl-2-yl-4-methyl-1-(2-morpholin-4-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-4-fluoro-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-4-fluoro-phenyl)-1-(2-dimethylamino-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-4-fluoro-phenyl)-4-methyl-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(2-morpholin-4-yl-ethyl)-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Diethylamino-ethyl)-4-methyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-5-(2-phenoxy-phenyl)-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-5-(2-phenoxy-phenyl)-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3-Dimethylamino-propyl)-4-methyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-ethyl)-4-methyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(4-Benzyloxy-2-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide.

5-(4-Hydroxy-2-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-[2-methyl-4-(3-morpholin-4-yl-propoxy)-phenyl]-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-[4-(3-morpholin-4-yl-propoxy)-2-trifluoromethyl-phenyl]-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide.

82. The compound of any one of claims 80 wherein R⁴ is:

83. The compound of claim 82 selected from the group consisting of:

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid [4-(2-fluoro-benzoyl)-phenyl]-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-3-trifluoromethyl-phenyl)-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-sulfamoyl-phenyl)-amide;

5-(4-fluoro-2-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-dimethyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (3-chloro-4-sulfamoyl-phenyl)-amide;

5-(4-fluoro-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(4-fluoro-2-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (3-chloro-4-sulfamoyl-phenyl)-amide;

5-(4-fluoro-2-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-sulfamoyl-3-trifluoromethyl-phenyl)-amide;

1,4-Dimethyl-5-(2-phenoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-(4-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Isopropoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-5-fluoro-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Butoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Benzyloxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Bromo-2-methoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Bromo-2-butoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

3-[4-(4-Methanesulfonyl-phenylcarbamoyl)-1,3-dimethyl-1H-pyrrol-2-yl]-benzoic acid methyl ester;

5-(3,5-Bis-trifluoromethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Isopropoxy-5-methyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Butoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(3-Benzylcarbamoyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Benzyloxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide; and

5-(3-Carbamoyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

N-[4-(aminosulfonyl)-3-chlorophenyl]-5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-1-(pyridin-3-ylmethyl)-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-1H pyrrole-3-carboxamide;

1-[3-(dimethylamino)propyl]-5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-2-ylmethyl)-1H-pyrrole-3-carboxamide;

1-[3-(dimethylamino)propyl]-5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-piperidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-[4-fluoro-2-(trifluoromethyl)phenyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide;

4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-3-ylmethyl)-1H-pyrrole-3-carboxamide;

4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide;

1-[2-(diethylamino)ethyl]-4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[(6-chloropyridin-2-yl)methyl]-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-1,4-dimethyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[(6-aminopyridin-2-yl)methyl]-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[2-(diethylamino)ethyl]-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

1-[(6-aminopyridin-2-yl)methyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-[(6-pyrrolidin-1-ylpyridin-2-yl)methyl]-1H-pyrrole-3-carboxamide;

5-(2,4-difluorophenyl)-4-methyl-1-[(6-methylpyridin-2-yl)methyl]-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

methyl(6-{[2-(2,4-difluorophenyl)-3-methyl-4-({[4-(methylsulfonyl)phenyl]amino}carbonyl)-1H-pyrrol-1-yl]methyl}pyridin-2-yl)carbamate;

1-{[6-(acetylamino)pyridin-2-yl]methyl}-5-(2,4-difluorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-({6-[bis(methylsulfonyl)amino]pyridin-2-yl}methyl)-5-(2,4-difluorophenyl)-4-methyl-N[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-{2-hydroxy-3-[(2-methylpropyl)amino]propyl}-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-{2-hydroxy-3-[(phenylmethyl)amino]propyl}-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(3-amino-2-hydroxypropyl)-5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-1-{2-[(2-methylpropyl)amino]-2-oxoethyl}-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(2-amino-2-oxoethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[2-(butylamino)-2-oxoethyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1,4-dimethyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-fluorophenyl)-1,4-dimethyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-piperidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-2-ylmethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-piperidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[3-(dimethylamino)propyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[2-(diethylamino)ethyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[(6-chloropyridin-2-yl)methyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-phenyl-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-4-ethyl-1-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-Fluoro-phenyl)-4-methyl-1-pyridin-2-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Fluoro-phenyl)-1-(2-hydroxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

N-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1,4-dimethyl-5 [2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-Chloro-phenyl)-4-methyl-1-pyrazin-2-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3-Fluoro-pyridin-2-ylmethyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(tetrahydro-furan-2-ylmethyl)-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(1-Hydroxy-2-methoxy-ethyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3,3-Dimethyl-2-oxo-butyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-Furan-2-ylmethyl-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid

(4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (3-chloro-4-sulfamoyl-phenyl)-amide;

(N-{4-[(acetylamino-kappaN)sulfonyl]-3-chlorophenyl}-1,4-dimethyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamidato)sodium;

1-(2-hydroxyethyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-pyrrolidin-1-ylethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-morpholin-4-ylethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(pyridin-2-ylmethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-[2-(diethylamino)ethyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-(2-piperidin-1-ylethyl)-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-[2-hydroxy-3-(phenyloxy)propyl]-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chlorophenyl)-1-(2,3-dihydroxypropyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-prop-2-en-1-yl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-phenyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(3-hydroxypropyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-{(2S)-3-[(4-fluorophenyl)oxy]-2-hydroxypropyl}-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

1-(4-hydroxybutyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

4-methyl-N-[4-(methylsulfonyl)phenyl]-1-[2-(tetrahydro-2H-pyran-2-yloxy)ethyl]-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

N-[4-(aminosulfonyl)-3-chlorophenyl]-1-(2-hydroxyethyl)-4-methyl-5-[2-(trifluoromethyl)phenyl]-1H-pyrrole-3-carboxamide;

5-(2-chloro-phenyl)-1-(2-Methoxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-chlorophenyl)-4-methyl-N-[4-(methylsulfonyl)phenyl]-1-prop-2-en-1-yl-1H-pyrrole-3-carboxamide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-(2-morpholin-4-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-1-(2-hydroxy-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-pyridin-3-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethyl-phenyl)-4-methyl-1-pyridin-2-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-[3-(4-Fluoro-phenoxy)-2-(R)-hydroxy-propyl]-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-Cyclopropylmethyl-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-prop-2-ynyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-[3-(4-fluoro-phenoxy)-2-(S)-hydroxy-propyl]-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-[3-(4-fluoro-phenoxy)-2-(R)-hydroxy-propyl]-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-cyclopropylmethyl-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-methyl-5-[2-(methyloxy)phenyl]-N-[4-(methylsulfonyl)phenyl-1 (2-piperidin-1-ylethyl)-1H-pyrrole-3-carboxamide;

5-(2-Methoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-methyl-amide;

5-(2-Methoxy-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methane sulfonyl-phenyl)-amide.

1,4-Dimethyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Diethylamino-ethyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(2-pyrrolidin-1-yl-ethyl)-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-pyridin-2-yl-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3-Dimethylamino-propyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

4-Methyl-1-(2-piperidin-1-yl-ethyl)-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide.

4-Methyl-1-(2-morpholin-4-yl-ethyl)-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide.

1-(2-Hydroxy-3-phenoxy-propyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Diethylamino-ethyl)-5-(2,6-difluoro-phenyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-ethyl)-4-methyl-5-o-tolyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Difluoro-phenyl)-4-methyl-1-(2-pyrrolidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Difluoro-phenyl)-4-methyl-1-(2-piperidin-1-yl-ethyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Difluoro-phenyl)-4-methyl-1-pyridin-2-ylmethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2,6-Dimethoxy-phenyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1,4-Dimethyl-5-(2-trifluoromethoxy-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-3-phenyl-propyl)-4-methyl-5-(2-trifluoromethyl-phenyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-2-phenyl-ethyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-3-methoxy-propyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-4-methyl-1-(3,3,3-trifluoro-2-hydroxy-propyl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(3-tert-Butoxy-2-hydroxy-propyl)-5-(2-chloro-phenyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

5-(2-Chloro-phenyl)-1-(2-hydroxy-3-isopropoxy-propyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide;

1-(2-Hydroxy-ethyl)-5-(4-methoxy-2-trifluoromethyl-phenyl)-4-methyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide.

84. The compound of any one of claims 80 wherein R⁴ is optionally substituted naphthyl.

85. The compound of claim 84 wherein said compound is selected from the group consisting of:

1,4-dimethyl-5-naphthalen-1-yl-1H-pyrrole-3-carboxylic acid (4-methane sulfonyl-phenyl)-amide; and

1,4-dimethyl-5-(4-methyl-naphthalen-1-yl)-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide.

86. The compound of claim 75 wherein R⁴ is hydrogen, —

C(O)R⁹ or —

S(O)₂R⁹;

where R⁹ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl.

87. The compound of claim 75 wherein R⁴ is alkyl, alkenyl or alkynyl, where each is optionally substituted by one or more substituents selected from the group consisting of halo, haloalkoxy, nitro, —

OR⁹, —

SR⁹, —

S(O)_tR¹⁰ (where t is 1 or

     2), —

N(R⁹)₂, —

CN, —

C(O)R⁹, —

C(S)R⁹, —

C(NR⁹)R⁹, —

C(O)OR⁹, —

C(S)OR⁹, —

C(NR⁹)OR⁹, —

C(O)N(R⁹)₂, —

C(S)N(R⁹)₂, —

C(NR⁹)N(R⁹)₂, —

C(O)SR⁹, —

C(S)SR⁹, —

C(NR⁹)SR⁹, —

S(O)_tOR⁹ (where t is 1 or

     2), —

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

S(O)_tN(R⁹)N═

C(R⁹)₂, —

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

N(R⁹)C(O)R¹⁰, —

N(R⁹)C(O)OR¹⁰, —

N(R⁹)C(O)SR¹⁰, —

N(R⁹)C(NR⁹)SR¹⁰, —

N(R⁹)C(S)SR¹⁰, —

N(R⁹)C(O)N(R⁹)₂, —

N(R⁹)C(NR⁹)N(R⁹)₂, —

N(R⁹)C(S)N(R⁹)₂, —

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

OC(O)R¹⁰, —

OC(NR⁹)R¹⁰, —

OC(S)R¹⁰, —

OC(O)OR¹⁰, —

OC(NR⁹)OR¹⁰, —

OC(S)OR¹⁰, —

OC(O)SR⁹, —

OC(O)N(R⁹)₂, —

OC(NR⁹)N(R⁹)₂, —

OC(S)N(R⁹)₂, —

C(O)—

R¹¹—

C(O)R⁹, —

C(O)—

R¹¹—

C(S)R⁹, —

C(O)—

R¹¹—

C(NR⁹)R⁹, —

C(O)—

R¹¹—

C(O)OR⁹, —

C(O)—

R¹¹—

C(S)OR⁹, —

C(O)—

R¹¹—

C(NR⁹)OR⁹, —

C(O)—

R¹¹—

C(O)N(R⁹)₂, —

C(O)—

R¹¹—

C(S)N(R⁹)₂, —

C(O)—

R¹¹C(NR⁹)N(R⁹)₂, —

C(O)—

R¹¹—

C(O)SR⁹, —

C(O)—

R¹¹—

C(S)SR⁹ and —

C(O)—

R¹¹—

C(NR⁹)SR⁹;

or R⁴ is cycloalkylalkyl, heterocyclylalkyl, aralkyl, or heteroaralkyl, where each is optionally substituted by one or more substituents selected from the group consisting of alkyl, alkenyl, alkynyl, halo, haloalkyl, haloalkenyl, haloalkoxy, nitro, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkenyl, optionally substituted cycloalkenylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted aralkenyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkenyl, optionally substituted heteroaryl, optionally substituted heteroaralkyl, optionally substituted heteroaralkenyl, —

R⁸—

OR⁹, —

R⁸—

SR⁹, —

R⁸—

S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

N(R⁹)₂, —

R⁸—

CN, —

R⁸—

C(O)R⁹, —

R⁸—

C(S)R⁹, —

R⁸—

C(NR⁹)R⁹, —

R⁸—

C(O)OR⁹, —

R⁸—

C(S)OR⁹, —

R⁸—

C(NR⁹)OR⁹, —

R⁸—

C(O)N(R⁹)₂, —

R⁸—

C(S)N(R⁹)₂, —

R⁸—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)SR⁹, —

R⁸—

C(S)SR⁹, —

R⁸—

C(NR⁹)SR⁹, —

R⁸—

S(O)_tOR⁹ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)N═

C(R⁹)₂, —

R⁸—

S(O)_tN(R⁹)C(O)R¹⁰ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(O)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

S(O)_tN(R⁹)C(NR⁹)N(R⁹)₂ (where t is 1 or

     2), —

R⁸—

N(R⁹)C(O)R¹⁰, —

R⁸—

N(R⁹)C(O)OR¹⁰, —

R⁸—

N(R⁹)C(O)SR¹⁰, —

R⁸—

N(R⁹)C(NR⁹)SR¹⁰, —

R⁸—

N(R⁹)C(S)SR¹⁰, —

R⁸—

N(R⁹)C(O)N(R⁹)₂, —

R⁸—

N(R⁹)C(NR⁹)N(R⁹)₂, —

R⁸—

N(R⁹)C(S)N(R⁹)₂, —

R⁸—

N(R⁹)S(O)_tR¹⁰ (where t is 1 or

     2), —

R⁸—

OC(O)R¹⁰, —

R⁸—

OC(NR⁹)R¹⁰, —

R⁸—

OC(S)R¹⁰, —

R⁸—

OC(O)OR¹⁰, —

R⁸—

OC(NR⁹)OR¹⁰, —

R⁸—

OC(S)OR¹⁰, —

R⁸—

OC(O)SR⁹, —

R⁸—

OC(O)N(R⁹)₂, —

R⁸—

OC(NR⁹)N(R⁹)₂, —

R⁸—

OC(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)R⁹, —

R⁸—

C(O)—

R¹¹—

C(S)R⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)R⁹, —

R⁸—

C(O)—

R¹¹—

C(O)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)OR⁹, —

R⁸—

C(O)—

R¹¹—

C(O)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(S)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(NR⁹)N(R⁹)₂, —

R⁸—

C(O)—

R¹¹—

C(O)SR⁹, —

R⁸—

C(O)—

R¹¹—

C(S)SR⁹ and —

R⁸—

C(O)—

R¹¹—

C(NR⁹)SR⁹;

where each R⁸ is independently a direct bond, an optionally substituted straight or branched alkylene chain, or an optionally substituted straight or branched alkenylene chain;

where each R⁹ is independently selected from the group consisting of hydrogen, optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl;

or

where two R⁹s, together with the nitrogen atom to which they are attached, form an optionally substituted heterocyclyl;

where each R¹⁰ is independently selected from the group consisting of optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted heteroaryl and optionally substituted heteroaralkyl; and

where each R¹¹ is independently an optionally substituted straight or branched alkylene chain or an optionally substituted straight or branched alkenylene chain.

88. The compound of claim 87 wherein said compound is:

5-((E)-3,3-dimethyl-but-1-enyl)-1,4-dimethyl-1H-pyrrole-3-carboxylic acid (4-methanesulfonyl-phenyl)-amide.

106. A method for the treatment of a disease, or disorder mediated by, or otherwise affected by one or more steroid nuclear receptors, or in which steroid nuclear receptor activity is implicated, comprising:

administering a pharmacologically active composition comprising a compound or pharmaceutically acceptable derivative thereof as set forth in claim 66, to a patient in need thereof.

107. The method of claim 106, wherein said disease or disorder is associated with an excess or a deficiency steroid receptor activity or endogenous regulators of said steroid receptor activity in said patient.

119. The method of claim 106, wherein said steroid nuclear receptor is the mineralocorticoid receptor.

120. A pharmaceutical composition comprising a compound of claim 66, and a pharmaceutically acceptable excipient.

121. The pharmaceutical composition of claim 120, further comprising one or more additional active ingredients.

122. The pharmaceutical composition of claim 121 wherein said one or more additional active ingredients are selected from the group consisting of ACE inhibitors, Angiotensin II blockers, anti-coagulants, anti-cancer agents, anti-arrhythmics, anti-inflammatory agents, beta blockers, calcium channel antagonists, lipid-modulating agents, cytokine antagonists, digitalis medicines, diuretics, endothelin blockers, vasodilators, immune-suppressants, and glucose lowering agents.

89-105. -105. (canceled)

108-118. -118. (canceled)

123-124. -124. (canceled)