Fused heterocyclic succinimide compounds and analogs thereof, modulators of nuclear hormone receptor function

Abstract

Fused cyclic compounds, methods of using such compounds in the treatment of nuclear hormone receptor-associated conditions such as cancer and immune disorders, and pharmaceutical compositions containing such compounds.

What we claim is:  
     
         1 . A compound of the following formula:  
       
         
           
           
               
               
           
         
       
       wherein the symbols have the following meanings and are, for each occurrence, independently selected: 
 G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;  
 Z 1  is O, S, NH, or NR 6 ;  
 Z 2  is O, S, NH, or NR 6 ;  
 A 1  is CR 7  or N;  
 A 2  is CR 7  or N;  
 Y′ is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is a bond or O, S, S═O, SO 2 , NH, NR 7 , CR 7 R 7′ , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, N═N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, or heterocyclo or substituted heterocyclo, and J″ is (CR 7 R 7′ )n and n=0-3, where Y is not a bond; and  
 W′ is CR 7 R 7′ —CR 7 R 7   7′ , CR 7 R 7′ —C═O, C═O—C═O, CR 7 R 7′ —C═CH 2 , C═CH 2 —C═CH 2 , CR 7 R 7′ —C═NR 1 , C═NR 1 —C═NR 1 , NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 NR 9′ , cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl, wherein when W′ is not NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 NR 9′ , or heterocyclo or substituted heterocyclo, then J′ must be O, S, S═O, SO 2 , NH, NR 7 , OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N; or  
 when W′ is CR 7 R 7′ —CR 7 R 7′ , the R 7  and R 7′ substituents in each occurrence may be taken together to form a substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring system which can be formed by any combination of R 7  and R 7′  attached to the same carbon atom;  
 Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1 or NR 4 R 5 ;  
 L is a bond, (CR 7 R 7′ )n, NH, NR 5 , NH (CR 7 R 7′ )n, or NR 5 (CR 7 R 7′ )n, where n=0-3;  
 R 1  and R 1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 3  and R 3′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenyl, heterocyclocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, hydroxylamine, hydroxamide, alkoxy or substituted alkoxy, amino, NR 1 R 2 , thiol, alkylthio or substituted alkylthio;  
 R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 OR 1 , SO 2 R 1  or SO 2 NR 1 R 1′ ;  
 R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalky, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SOR 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, hydroxylamine, hydroxylamide, amino, NHR 4 , NR 2 R 5 , NR 5 R 5 , NOR 1 , thiol, alkylthio or substituted alkylthio, HOC═O, R 1 C═O, R 1 (C═O)O, R 1 OC═O, R 1 NHC═O, NH 2 C═O, SO 2 R 1 , SOR 1 , PO 3 R 1 R 1′ , R 1 R 1′ NC═O, C═OSR 1 , SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ , or, wherein A 1  or A 2  contains a group R 7  and W contains a group R 7 , said R 7  groups of A 1  or A 2  and W together form a heterocyclic ring;  
 R 8  and R 8′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, nitro, halo, CN, OR 1 , amino, NHR 4 , NR 2 R 5 , NOR 1 , alkylthio or substituted alkylthio, C═OSR 1 , R 1 OC═O, R 1 C═O, R 1 NHC═O, R 1 R 1′ NC═O, SO 2 OR 1 , S═OR 1 , SO 2 R 1 , PO 3 R 1 R 1′ , or SO 2 NR 1 R 1′ ; and  
 R 9  and R 9′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 with the provisos that: 
 (1) when Y′ is —O—, Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is —CH 2 —CH 2 —, and A 1  and A 2  are CH, then G—L is not phenyl, monosubstituted phenyl or phenyl which is substituted with two or more of the following groups: methoxy, halo, NO 2 , methyl, CH 3 —S—, OH, CO 2 H, trifluoromethyl, —C(O)—C 6 H 5 , NH 2 , 4-7-epoxy, hexahydro-1H-isoindole-1,3(2H)dione, or —C(O)—CH 3 ;  
 (2) when Y′ is —O—, Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is CH 2 —CH 2 , and one of A 1  and A 2  is CH and the other is CR 7 , then G—L is not unsubstituted phenyl;  
 (3) when Y′ is —O—, Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is CH 2 —CH 2 , and one of A 1  and A 2  is CH and the other is C—CH 3 , then G—L is not phenyl substituted with chloro and/or methyl;  
 (4) when Y′ is —O— or —S—, Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is CH 2 —CH 2 , and one of A 1  and A 2  is CH and the other is CH or C-alkyl, then G—L is not N-substituted piperazine-alkyl- or N-substituted imidazolidine-alkyl-;  
 (5) when Y′ is —O—; Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is CH 2 -CH 2 , and A 1  and A 2  are CH, then G—L is not oxazole or triazole;  
 (6) when Y′ is —O—; Q 1  and Q 2  are hydrogen or methyl, Z 1  and Z 2  are O, W′ is CH 2 —CH 2 , and A 1  and A 2  are CH or C—CH 3 , then G—L is not thiazole or substituted thiazole;  
 (7) when Y′ contains a group J′ selected from S, S═O, SO 2 , NH, NR 7 , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHR 6 , NR 6 NH or N═N, W′ is CR 7 R 7′ —CR 7 R 7′ , and Z 1  and Z 2  are O, then G—L is not unsubstituted phenyl;  
 (8) when Y is NR 7 , W′ is unsubstituted or substituted phenyl, and Q 1  and Q 2  are hydrogen, then Z 1  and Z 2  are not O;  
 (9) when Y′ is —O—, Q 1  and Q 2  are hydrogen, Z and Z   2  are O, W′ is dihydroisoxazole bearing an optionally substituted phenyl group, and A 1  and A 2  are CH, then G—L is not unsubstituted phenyl or dichlorophenyl;  
 (10) when Y′ is O, Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is ethylene oxide, and A 1  and A 2  are CH, then G—L is not methylphenyl or chlorophenyl;  
 (11) when Y′ is NR 7 —CR 7 R 7′ , W′ is CR 8 ═CR 8′ , Q 1  and Q 2  are hydrogen, A 1  and A 2  are CH, C—CH 3 , C—CH 2 —C 6 H 5  or C—CH 2 —CH 3 , and Z 1  and Z 2  are O, then G—L is not unsubstituted phenyl, monosubstituted phenyl or methylpyridinyl;  
 (12) when Y′ is CR 7 R 7′ —C═O, W′ is NR 9 —CR 7 R 7′ , Q 1  Q 2  are hydrogen, A 1  and A 2  are CH, and Z 1  and Z 2  are O, then G—L is not unsubstituted phenyl;  
 (13) when Y′ is CHR 7′ —NR 7  where R 7′  is unsubstituted phenyl, methoxy or ethoxy and R 7  is unsubstituted phenyl, methyl or —C(O)—C 6 H 5 , W′ is dimethoxyphenylene or unsubstituted phenylene, Z 1  and Z 2  are O, Q 1  and Q 2  are hydrogen, A 1  and A 2  are CH, C—CN, C—C(O)—C 6 H 5 , or —C(O)— dimethoxyphenyl, then G—L is not unsubstituted phenyl;  
 (14) the compound of formula Ia is not 6,10-epithio-4H-thieno-[3′,4′:5,6]cyclooct[1,2-f]isoindole-7,9(5H,8H)dione, 8-(3,5-dichlorophenyl)-6,6a,9a,10,11,12,-hexahydro-1,3,6,10-tetramethyl-2,2,13-trioixde, (6R,6aR,9aS,10S);  
 (15) when Y′ is O, W′ is —CH 2 —CH 2 —, Q 1  and Q 2  are methyl, Z 1  and Z 2  are O, and A 1  and A 2  are CH, then G—L is not unsubstituted phenyl, phenyl substituted with methoxy, phenyl-alkyl-, or morpholine-alkyl, nor is the compound bridged to itself through a group L which is alkylene to form a bis compound;  
 (16) when Y′ is —O—, Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is CR 7 R 7′ —CR 7 R 7′ , and A 1  and A 2  are CH, then G—L is not an unsubstituted phenyl group; and  
 (17) when Y′ is —O—, Q 1  and Q 2  are hydrogen, Z 1  and Z 2  are O, W′ is cyclopentyl, cyclohexyl, 3-phenyl-2-isoxazoline or CR 7 R 7′ —CR 7 R 7′  where R 7  and R 7 ′ are each independently defined as Cl, Br, H and 4-butyrolactone and R 7  and R 7 ′ are not all simultaneously H, and A 1  and A 2  are CH, then G—L is not an unsubstituted naphthyl ring or a monosubstituted phenyl ring, where said substituent is methoxy, Br, Cl, NO 2 , methyl, ethyl, CH 2 -phenyl, S-phenyl, or O-phenyl;  
 or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof.  
 
 
     
     
         2 . The compound of  claim 1  wherein 
 G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;  
 Z 1  is O, S, NH, or NR 6 ;  
 Z 2  is O, S, NH, or NR 6 ;  
 A 1  is CR 7  or N;  
 A 2  is CR 7  or N;  
 Y′ is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is a bond or O, S, S═O, SO 2 , NH, NR 7 , CR 7 R 7′ , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, N═N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, or heterocyclo or substituted heterocyclo, and J″ is (CR 7 R 7′ )n and n=0-3, where Y′ is not a bond;  
 W′ is CR 7 R 7′ —CR 7 R 7′ , CR 7 R 7′ —C═O, C═O—C═O, CR 7 R 7′ —C═CH 2 , C═CH 2 —C═CH 2 , CR 7 R 7′ —C═NR 1 , C═NR 1 —C═NR 1 , NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 NR 9′ , cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl, wherein when W′ is not NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , or heterocyclo or substituted heterocyclo, then J′ must be O, S, S═O, SO 2 , NH, NR 7 , OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N; or  
 when W′ is CR 7 R 7′ —CR 7 R 7′ , the R 7  and R 7′  substituents in each occurrence may be taken together to form a substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring system which can be formed by any combination of R 7  and R 7′  attached to the same carbon atom;  
 Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , or NR 4 R 5 ;  
 Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , or NR 4 R 5 ;  
 L is a bond, (CR 7 R 7′ )n, NH, NR 5  or NR 5 (CR 7 R 7′ )n, where n=0-3;  
 R 1  and R 1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 3  and R 3′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, hydroxylamine, hydroxamide, alkoxy or substituted alkoxy, amino, NR 1 R 2 , thiol, alkylthio or substituted alkylthio;  
 R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, or SO 2 NR 1 R 1′ ;  
 R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , or SO 2 NR 1 R 1′ ;  
 R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SO 2 R 1 , or SO 2 NR 1 R 1′ ;  
 R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, hydroxylamine, hydroxylamide, amino, NHR 4 , NR 2 R 5 , NOR 1 , thiol, alkylthio or substituted alkylthio, R 1 C═O, R 1 (C═O)O, R 1 OC═O, R 1 NHC═O, SOR 1 , PO 3 R 1 R 1′ , R 1 R 1′ NC═O, C═OSR 1 , SO 2 R 1 , or SO 2 NR 1 R 1′ ;  
 R 8  and R 8′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, nitro, halo, CN, OR 1 , amino, NHR 4 , NR 2 R 5 , NOR 1 , alkylthio or substituted alkylthio, C═OSR 1 , R 1 OC═O, R 1 C═O, R 1 NHC═O, R 1 R 1′ NC═O, S═OR 1 , SO 2 R 1 , PO 3 R 1 R 1′ , or SO 2 NR 1 R 1′ ;  
 R 9  and R 9′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl; cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 OC═O, R 1 NHC═O, or SO 2 NR 1 R 1′ ;  
 with the provisos (1) to (17) of said formula Ia, and further where (i) when Y′ is —O— and W′ is CR 7 R 7′ —CR 7 R 7′ , A 1  and A 2  are not simultaneously CH; and (ii) when L is a bond, G is not an unsubstituted phenyl group;  
 or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof.  
 
     
     
         3 . The compound of  claim 1 , wherein 
 G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;    Z 1  is O;    Z 2  is O;    A 1  is CR 7 ;    A 2  is CR 7 ;    Y′ is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is a bond or O, S, S═O, SO 2 , NH, NR 7 , CR 7 R 7′ , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, N═N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, or heterocyclo or substituted heterocyclo, and J″ is (CR 7 R 7′ )n and n=0-3, where Y′ is not a bond;    W′ is CR 7 R 7′ —CR 7 R 7′ , CR 7 R 7′ —C═O, C═O—C═O, CR 7 R 7′ —C═CH 2 , C═CH 2 —C═CH 2 , CR 7 R 7′—C═NR   1 , C═NR 1 —C═NR 1 , NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl, wherein when W′ is not NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , or heterocyclo or substituted heterocyclo, then J′ must be O, S, S═O, SO 2 , NH, NR 7 , OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N; or    when W′ is CR 7 R 7′ —CR 7 R 7′ , the R 7  and R 7′  substituents in each occurrence may be taken together to form a substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring system which can be formed by any combination of R 7  and R 7′  attached to the same carbon atom;    Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , or NR 4 R 5 ;    Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , or NR 4 R 5 ;    L is a bond;    R and R   1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;    R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;    R 3  and R 3′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, alkoxy or substituted alkoxy, amino, NR 1 R 2 , alkylthio or substituted alkylthio;    R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, or SO 2 NR 1 R 1′ ;    R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , or SO 2 NR 1 R 1′ ;    R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SO 2 R 1 , or SO 2 NR 1 R 1′ ;    R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, amino, NHR 4 , NR 2 R 5 , alkylthio or substituted alkylthio, R 1 C═O, R 1 (C═O)O, R 1 NHC═O, SO 2 R 1 , R 1 R 1′ NC═O, or SO 2 NR 1 R 1′ ;    R 8  and R 8′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, nitro, halo, CN, OR 1 , amino, NHR 4 , NR 2 R 5 , alkylthio or substituted alkylthio, R 1 C═O, R 1 NHC═O, R 1 R 1′ NC═O, SO 2 R 1 , or SO 2 NR 1 R 1′ ; and    R 9  and R 9′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, or SO 2 NR 1 R 1′ ;    with the provisos (1) to (17) of said formula Ia, and further where (i) when Y′ is —O— and W′ is CR 7 R 7′ —CR 7 R 7′ , A 1  and A 2  are not simultaneously CH; and (ii) when L is a bond, G is not an unsubstituted phenyl group;    or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof.    
     
     
         4 . A compound selected from the group consisting of: 
 (3aα,4β,5β,7β,7aα)-4-[Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-1-isoquinolinecarbonitrile (748D);    [3aS-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile (471Di) or [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile (471Dii);    [3aS-(3aα,4β,5β,7β,7aα)]-5-[7-[2-[[3-Chloro-5-(trifluoromethyl)-2-pyridinyl]oxy]ethyl]octahydro-5-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (744);    [3aS-(3aα,4β,5β,7β,7aα)]-5-[7-[2-(3-Fluorophenoxy)ethyl]octahydro-5-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (745);    [3aS-(3aα,4β,5β,7β,7aα)]-5-[7-[2-(1,3-Benzodioxol-5-yloxy)ethyl]octahydro-5-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-5-[7-[2-(4-Fluorophenoxy)ethyl]octahydro-5-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-5-[7-[2-(1,2-Benzisoxazol-3-yloxy)ethyl]octahydro-5-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-5-[7-[2-[(5-Chloro-1,2-benzisoxazol-3-yl)oxy]ethyl]octahydro-5-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (737);    [3aS-(3aα,4β,7β,7aα)]-5-[4-[2-[(5-Chloro-2-pyridinyl)oxy]ethyl]octahydro-7-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (577);    [3aS-(3aα,4β,7β,7aα)]-5-[Octahydro-4-methyl-1,3-dioxo-7-[2-[[6-(trifluoromethyl)-4-pyrimidinyl]oxy]ethyl]-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (579);    [3aS-(3aα,4β,7β,7aα)]-5-[4-[2-[(5-Chloro-1,2-benzisoxazol-3-yl)oxy]ethyl]octahydro-7-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (581);    [3aS-(3aα,4β,7β,7aα)]-5-[Octahydro-4-methyl-7-[2-(5-methyl-2H-1,2,3-benzotriazol-2-yl)ethyl]-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (589);    [3aS-(3aα,4β,5β,7β,7aα)]-5-[Octahydro-5-hydroxy-4-methyl-1,3-dioxo-7-[2-[[6-(trifluoromethyl)-4-pyrimidinyl]oxy]ethyl]-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (689);    [3aR-(3aα,4β,7β,7aα)]-5-[7-[2-[(5-Chloro-2-pyridinyl)oxy]ethyl]octahydro-5-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-8-quinolinecarbonitrile (487);    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile (489Gi);    [3aS-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile (489Gii);    (3aα,4β,7β,7aα)-4-(Octahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-1,2-benzenedicarbonitrile (313);    (3aα,4β,7β,7aα)-2-Methoxy-4-(octahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)benzonitrile (328);    (3aα,4β,7β,7aα)-5-(Octahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-8-quinolinecarbonitrile (345);    (3aα,4β,7β,7aα)-2-(Methylthio)-4-(octahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)benzonitrile (224);    (3aα,4β,7β,7aα)-2-(6-Benzothiazolyl)hexahydro-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione (368);    (3aα,4β,7β,7aα)-7-[Octahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl]-2,1,3-benzoxadiazole-4-carbonitrile (423); and    (3aα,4β,7β,7aα)-2-(2,1,3-Benzoxadiazol-5-yl)hexahydro-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione (480B);    or a pharmaceutically acceptable salt, solvate or prodrug thereof.    
     
     
         5 . A compound selected from the group consisting of: 
 [3aS-(3aα,4β,6β,7β,7aα)]-4-(Octahydro-6-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,6β,7β,7aα)]-4-(Octahydro-6-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,5β,6α,7β,7aα)]-4-(Octahydro-5,6-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-5-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3methyl-2-pyridinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-2-(2,1,3-Benzoxadiazol-5-yl)hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    [3aS-(3aα,4β,5β,7β,7aα)]-5-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3,4-dimethyl-2-pyridinecarbonitrile;    [3aR-(3aα,4β,5β,7β,7aα)]-5-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3,4-dimethyl-2-pyridinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-2-(6-Benzothiazolyl)hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    [3aR-(3aα,4β,5β,7β,7aα)]-2-(7-Chloro-2,1,3-benzoxadiazol-4-yl) hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    [3aR-(3aα,4β,5α,7β,7aα)]-5-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3-(trifluoromethyl)-2-pyridinecarbonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile;    (3aα,4β,5α,6β,7β,7aα)-2-(4-Cyano-3-(trifluoromethyl)phenyl)hexahydro-6-cyano-4,7-dimethyl-1,3-dioxo-4,7-epoxy-1H-isoindole-5-carboxylic acid, methyl ester;    (3aα,4β,7β,7aα)-4-(Octahydro-4,7,8-trimethyl-1,3-dioxo-4,7-imino-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5β,6α,7β,7aα)]-4-(Octahydro-5,6-dichloro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,5β,6α,7β,7aα)]-4-(Octahydro-5,6-dichloro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,7β,7aα)-4-(Octahydro-4,7-dimethyl-1,3,5-trioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[[difluoromethyl]oxy]methyl]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[phenylmethoxycarbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[propyloxycarbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[[cyclopropylmethyloxy]carbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[methoxycarbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2,3-dichlorobenzonitrile;    [3aR-(3aα,4β,4aα,5aα,6β,7aα)]-4-(Octahydro-4a-hydroxy-4,6-dimethyl-1,3-dioxo-4,6-epoxycycloprop[f]isoindol-2(1 H)-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-2-(4-Cyano-3-(trifluoromethyl)phenyl)hexahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-N,N-dimethyl-1H-isoindole-5-carboxamide;    [3aR-(3aα,4β,5β,6β,7β,7aα)]-4-(Octahydro-5-chloro-6-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,5β,6β,7β,7aα)]-4-(Octahydro-5-chloro-6-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[[6-(trifluoromethyl)-4-pyrimidinyl]oxy]methyl]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[[5-chloro-2-pyridinyl]oxy]methyl]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[[phenylamino]carbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[(1-methylethyloxy)carbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[[5-fluoro-4-pyrimidinyl]oxy]methyl]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[ethyloxycarbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-2-(4-Cyano-3-(trifluoromethyl)phenyl)-hexahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-1H-isoindole-5-carboxylic acid, 4-pyridinylmethyl ester;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[4-pyridinylmethoxycarbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    3aα,4β,5β,7β,7aα)-4-(Octahydro-5-[[[2-methyl-5-(trifluoromethyl)-2H-pyrazol-3-yl]oxy]methyl]-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-2-(4-Cyano-3-(trifluoromethyl)phenyl)hexahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-1H-isoindole-5-carboxylic acid, methyl ester;    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-cyclopropylmethoxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[((phenylmethyl)amino)carbonyl]oxy]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile; and    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-cyclopropyloxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    or a pharmaceutically acceptable salt, solvate or prodrug thereof.    
     
     
         6 . A compound selected from the group consisting of: 
 [3aR-(3aα,4β,5β,7β,7aα)]-5-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3-(trifluoromethyl)-2-pyridinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-5-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3-(trifluoromethyl)-2-pyridinecarbonitrile;    [3aR-(3aα,4β,5β,7β,7aα)]-2-(4-Chloro-3-iodophenyl)hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    [3aS-(3aα,4β,5β,6α,7β,7aα)]-4-(Octahydro-5 ,6-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,7β,7aα)]-4-(Octahydro-4,7-dimethyl-1,3,5-trioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,6β,7β,7aα)]-4-(Octahydro-6-hydroxy-4-methyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5β,7β,7aα)]-2-(4-Chloro-3-(trifluoromethyl)phenyl)hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    [3aS-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile;    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-2-(4-Chloro-3-(trifluoromethyl)pyridinyl)hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3-methyl-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-methoxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-5-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3-(trifluoromethyl)-2-pyridinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-methoxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,6β,7β,7aα)]-4-(Octahydro-6-fluoro-5,5-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,7β,7aα)]-5-(Octahydro-4,7-dimethyl-1,3,5-trioxo-4,7-epoxy-2H-isoindol-2-yl)-3-(trifluoromethyl)-2-pyridinecarbonitrile;    [3aS-(3aα,4β,5β,7β,7aα)]-2-(4-Chloro-2-methyl-3-(trifluoromethyl)phenyl)hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    [3aR-(3aα,4β,5β,7β,7aα)]-2-(4-Chloro-2-methyl-3-(trifluoromethyl)phenyl)hexahydro-5-hydroxy-4,7-dimethyl-4,7-epoxy-1H-isoindole-1,3(2H)-dione;    (3aα,4β,6β,7β,7aα)-4-(Octahydro-6-fluoro-5,5-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile;    (3aα,4β,5α,7β,7aα)-2-(4-Cyano-3-(trifluoromethyl)phenyl)-hexahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-1H-isoindole-5-carboxylic acid, methyl ester;    [3aS-(3aα,4β,6β,7β,7aα)]-4-(Octahydro-6-fluoro-5,5-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-ethylsulfonamido-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[(4-fluorophenylamino)carbonyl]oxy]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[(1-methylethylamino)carbonyl]oxy]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[(1-methylethoxy)carbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,6β,7β,7aα)]-4-(Octahydro-6-fluoro-5,5-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-iodobenzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-2-(4-Cyano-3-(trifluoromethyl)phenyl)hexahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-N-methyl-N-phenyl-1H-isoindole-5-carboxamide;    [3aR-(3aα,4β,5β,7β,7aα)]-4-(Octahydro-5-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-chloro-3-methylbenzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[ethoxycarbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[[2-methyl-5-(trifluoromethyl)-2H-pyrazol-3-yl]oxy]methyl]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aS-(3aα,4β,5α,6β,7β,7aα)]-2-(4-Cyano-3-(trifluoromethyl)phenyl)-hexahydro-6-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-1H-isoindole-5-carboxylic acid, methyl ester;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-[[[6-(trifluoromethyl)-4-pyrimidinyl]oxy]methyl]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-methoxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-2-(4-Cyano-3-(trifluoromethyl)phenyl)-hexahydro-4,7-dimethyl-1,3-dioxo-4,7-epoxy-1H-isoindole-5-carbonitrile;    [3aR-(3aα,4β,5β,6α,7β,7aα)]-4-(Octahydro-5,6-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-3-methyl-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[[(cyclopropylmethyl)amino]carbonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[(dimethylamino)sulfonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    (3aα,4β,5α,7β,7aα)-4-(Octahydro-5-benzenesulfonamido-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,6β,7β,7aα)]-4-(Octahydro-6-fluoro-5,5-dihydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    [3aR-(3aα,4β,5α,6β,7β,7aα)]-2-(4-Cyano-3-(trifluoromethyl)phenyl)-hexahydro-6-hydroxy-4,7-dimethyl-1,3-dioxo-4,7-epoxy-1H-isoindole-5-carboxylic acid, methyl ester; and    [3aR-(3aα,4β,5α,7β,7aα)]-4-(Octahydro-5-[[(dimethylamino)sulfonyl]amino]-4,7-dimethyl-1,3-dioxo-4,7-epoxy-2H-isoindol-2-yl)-2-(trifluoromethyl)benzonitrile;    or a pharmaceutically acceptable salt, solvate or prodrug thereof.    
     
     
         7 . A pharmaceutical composition capable of treating a NHR-associated condition, comprising at least one compound of the following formula I or a pharmaceutically acceptable salt, solvateor prodrug thereof, and a pharmaceutically acceptable carrier:  
       
         
           
           
               
               
           
         
       
       wherein the symbols have the following meanings and are, for each occurrence, independently selected: 
 G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;  
 Z 1  is O, S, NH, or NR 6 ;  
 Z 2  is O, S, NH, or NR 6 ;  
 A 1  is CR 7  or N;  
 A 2  is CR 7  or N;  
 Y is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is a bond or O, S, S═O, SO 2 , NH, NR 7 , C═O, OC═O, NR 1 C═O, CR 7 R 7′ , C═CR 8 R 8′ , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OP═OR 2 , OSO 2 , C═NR 7 , NHNH, NHNR 6 , NR 6 NH, N═N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo or aryl or substituted aryl, and J″ is (CR 7 R 7′ )n and n=0-3, where Y is not a bond;  
 W is CR 7 R 7′ —CR 7 R 7′ , CR 8 ═CR 8′ , CR 7 R 7′ —C═O, C═O—C═O, CR 7 R 7′ —C═CH 2 , C═CH 2 —C═CH 2 , CR 7 R 7′ —C═NR 1 , C═NR 1 —C═NR 1 , NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , S—CR 7 R 7′ , SO—CR 7 R 7′ , SO 2 —CR 7 R 7′ , cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl, wherein when W is not NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , S—CR 7 R 7′ , SO—CR 7 R 7′ , SO 2 —CR 7 R 7′ , or heterocyclo or substituted heterocyclo, then J′ must be O, S, S═O, SO 2 , NH, NR 7 , OC═O, NR 1 C═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N; or  
 when W is CR 7 R 7′ —CR 7 R 7′ , the R 7  and R 7′  substituents in each occurrence may be taken together to form a substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring system which can be formed by any combination of R 7  and R 7′  attached to the same carbon atom;  
 Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 L is a bond, (CR 7 R 7′ )n, NH, NR 5 , NH(CR 7 R 7′ )n, or NR 5 (CR 7 R 7′ )n, where n=0-3;  
 R 1  and R 1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 3  and R 3′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, hydroxylamine, hydroxamide, alkoxy or substituted alkoxy, amino, NR 1 R 2 , thiol, alkylthio or substituted alkylthio;  
 R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 OR 1 , SO 2 R 1  or SO 2 NR 1 R 1′ ;  
 R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, hydroxylamine, hydroxylamide, amino, NHR 4 , NR 2 R 5 , NR 5 R 5 , NOR 1 , thiol, alkylthio or substituted alkylthio, HOC═O, R 1 C═O, R 1 (C═O)O, R 1 OC═O, R 1 NHC═O, NH 2 C═O, SO 2 R 1 , SOR 1 , PO 3 R 1 R 1′ , R 1 R 1′ NC═O, C═OSR 1 , SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ , or, wherein A 1  or A 2  contains a group R 7  and W contains a group R 7 , said R 7  groups of A 1  or A 2  and W together form a heterocyclic ring;  
 R 8  and R 8′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, nitro, halo, CN, OR 1 , amino, NHR 4 , NR 2 R 5 , NOR 1 , alkylthio or substituted alkylthio, C═OSR 1 , R 1 OC═O, R 1 C═O, R 1 NHC═O, R 1 R 1′ NC═O, SO 2 OR 1 , S═OR 1 , SO 2 R 1 , PO 3 R 1 R 1′ , or SO 2 NR 1 R 1′ ; and  
 R 9  and R 9′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ .  
 
     
     
         8 . A pharmaceutical composition of  claim 7  further comprising another anti-cancer agent.  
     
     
         9 . A pharmaceutical composition capable of treating a NHR-associated condition, comprising at least one compound as defined in  claim 2  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
     
     
         10 . A pharmaceutical composition of  claim 9  further comprising another anti-cancer agent.  
     
     
         11 . A pharmaceutical composition capable of treating a NHR-associated condition, comprising at least one compound as defined in  claim 3  or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.  
     
     
         12 . A pharmaceutical composition of  claim 11  further comprising another anti-cancer agent.  
     
     
         13 . A method of modulating the function of a nuclear hormone receptor which comprises administering to a mammalian species in need thereof an effective nuclear hormone receptor modulating amount of at least one compound of the following formula I:  
       
         
           
           
               
               
           
         
       
       wherein the symbols have the following meanings and are, for each occurrence, independently selected: 
 G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;  
 Z 1  is O, S, NH, or NR 6 ;  
 Z 2  is O, S, NH, or NR 6 ;  
 A 1  is CR 7  or N;  
 A 2  is CR 7  or N;  
 Y is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is a bond or O, S, S═O, SO 2 , NH, NR 7 , C═O, OC═O, NR 1 C═O, CR 7 R 7′ , C═CR 8 R 8′ , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OP═OR 2 , OSO 2 , C═NR 7 , NHNH, NHNR 6 , NR 6 NH, N═N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo or aryl or substituted aryl, and J″ is (CR 7 R 7′ )n and n=0-3, where Y is not a bond;  
 W is CR 7 R 7′ —CR 7 R 7′ , CR 8 ═CR 8′ , CR 7 R 7′ —C═O, C═O—C═O, CR 7 R 7′ —C═CH 2 , C═CH 2 —C═CH 2 , CR 7 R 7′ —C═NR 1 , C═NR 1 —C═NR 1 , NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , S—CR 7 R 7′ , SO—CR 7 R 7′ , SO 2 —CR 7 R 7′ , cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl, wherein when W is not NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , S—CR 7 R 7′ , SO—CR 7 R 7′ , SO 2 —CR 7 R 7′ , or heterocyclo or substituted heterocyclo, then J′ must be O, S, S═O, SO 2 , NH, NR 7 , OC═O, NR 1 C═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N; or  
 when W is CR 7 R 7′ —CR 7 R 7′ , the R 7  and R 7′  substituents in each occurrence may be taken together to form a substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring system which can be formed by any combination of R 7  and R 7′  attached to the same carbon atom;  
 Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 L is a bond, (CR 7 R 7′ )n, NH, NR 5 , NH(CR 7 R 7′ )n, or NR 5 (CR 7 R 7′ )n, where n=0-3;  
 R 1  and R 1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 3  and R 3′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, hydroxylamine, hydroxamide, alkoxy or substituted alkoxy, amino, NR 1 R 2 , thiol, alkylthio or substituted alkylthio;  
 R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 OR 1 , SO 2 R 1  or SO 2 NR 1 R 1′ ;  
 R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, hydroxylamine, hydroxylamide, amino, NHR 4 , NR 2 R 5 , NR 5 R 5 , NOR 1 , thiol, alkylthio or substituted alkylthio, HOC═O, R 1 C═O, R 1 (C═O)O, R 1 OC═O, R 1 NHC═O, NH 2 C═O, SO 2 R 1 , SOR 1 , PO 3 R 1 R 1′ , R 1 R 1′ NC═O, C═OSR 1 , SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ , or, wherein A 1  or A 2  contains a group R 7  and W contains a group R 7 , said R 7  groups of A 1  or A 2  and W together form a heterocyclic ring;  
 R 8  and R 8′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, nitro, halo, CN, OR 1 , amino, NHR 4 , NR 2 R 5 , NOR 1 , alkylthio or substituted alkylthio, C═OSR 1 , R 1 OC═O, R 1 C═O, R 1 NHC═O, R 1 R 1′ NC═O, SO 2 OR 1 , S═OR 1 , SO 2 R 1 , PO 3 R 1 R 1′ , or SO 2 NR 1 R 1′ ; and  
 R 9  and R 9′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof.  
 
     
     
         14 . The method of  claim 13  wherein said nuclear hormone receptor is a steroid binding nuclear hormone receptor.  
     
     
         15 . The method of  claim 13  wherein said nuclear hormone receptor is the androgen receptor.  
     
     
         16 . The method of  claim 13  wherein said nuclear hormone receptor is the estrogen receptor.  
     
     
         17 . The method of  claim 13  wherein said nuclear hormone receptor is the progesterone receptor.  
     
     
         18 . The method of  claim 13  wherein said nuclear hormone receptor is the glucocorticoid receptor.  
     
     
         19 . The method of  claim 13  wherein said nuclear hormone receptor is the mineralocorticoid receptor.  
     
     
         20 . The method of  claim 13  wherein said nuclear hormone receptor is the aldosterone receptor.  
     
     
         21 . The method of  claim 13  wherein said nuclear hormone receptor is the RORbeta receptor.  
     
     
         22 . The method of  claim 13  wherein said nuclear hormone receptor is the COUP-TF2 receptor.  
     
     
         23 . A method for treating a condition or disorder comprising administering to a mammalian species in need thereof a therapeutically effective amount of at least one compound of the following formula:  
       
         
           
           
               
               
           
         
       
       or a pharmceutically acceptable salt, solvate, prodrug or stereoisomer thereof, wherein the symbols have the following meanings and are, for each occurrence, independently selected: 
 G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;  
 Z 1  is O, S, NH, or NR 6 ;  
 Z 2  is O, S, NH, or NR 6 ;  
 A 1  is CR 7  or N;  
 A 2  is CR 7  or N;  
 Y is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is a bond or O, S, S═O, SO 2 , NH, NR 7 , C═O, OC═O, NR 1 C═O, CR 7 R 7′ , C═CR 8 R 8′ , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OP═OR 2 , OSO 2 , C═NR 7 , NHNH, NHNR 6 , NR 6 NH, N═N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo or aryl or substituted aryl, and J″ is (CR 7 R 7′ )n and n=0-3, where Y is not a bond;  
 W is CR 7 R 7′ —CR 7 R 7′ , CR 8 ═CR 8′ , CR 7 R 7′ —C═O, C═O—C═O, CR 7 R 7′ —C═CH 2 , C═CH 2 —C═CH 2 , CR 7 R 7′ —C═NR 1 , C═NR 1 —C═NR 1 , NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , S—CR 7 R 7′ , SO—CR 7 R 7′ , SO 2 —CR 7 R 7′ , cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl, wherein when W is not NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , S—CR 7 R 7′ , SO—CR 7 R 7′ , SO 2 —CR 7 R 7′ , or heterocyclo or substituted heterocyclo, then J′ must be O, S, S═O, SO 2 , NH, NR 7 , OC═O, NR 1 C═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N; or  
 when W is CR 7 R 7′ —CR 7 R 7′ , the R 7  and R 7′  substituents in each occurrence may be taken together to form a substituted or unsubstituted carbocyclic or substituted or unsubstituted heterocyclic ring system which can be formed by any combination of R 7  and R 7′  attached to the same carbon atom;  
 Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo (e.g., heteroaryl) or substituted heterocyclo (e.g., substituted heteroaryl), halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 L is a bond, (CR 7 R 7′ )n, NH, NR 5 , NH(CR 7 R 7′ )n, or NR 5 (CR 7 R 7′ )n, where n=0-3;  
 R 1  and R 1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 3  and R 3′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, hydroxylamine, hydroxamide, alkoxy or substituted alkoxy, amino, NR 1 R 2 , thiol, alkylthio or substituted alkylthio;  
 R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 OR 1 , SO 2 R 1  or SO 2 NR 1 R 1′ ;  
 R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, hydroxylamine, hydroxylamide, amino, NHR 4 , NR 2 R 5 , NR 5 R 5 , NOR 1 , thiol, alkylthio or substituted alkylthio, HOC═O, R 1 C═O, R 1 (C═O)O, R 1 OC═O, R 1 NHC═O, NH 2 C═O, SO 2 R 1 , SOR 1 , PO 3 R 1 R 1′ , R 1 R 1′ NC═O, C═OSR 1 , SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ , or, wherein A 1  or A 2  contains a group R 7  and W contains a group R 7 , said R 7  groups of A 1  or A 2  and W together form a heterocyclic ring;  
 R 8  and R 8′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, nitro, halo, CN, OR 1 , amino, NHR 4 , NR 2 R 5 , NOR 1 , alkylthio or substituted alkylthio, C═OSR 1 , R 1 OC═O, R 1 C═O, R 1 NHC═O, R 1 R 1′ NC═O, SO 2 OR 1 , S═OR 1 , SO 2 R 1 , PO 3 R 1 R 1′ , or SO 2 NR 1 R 1′ ; and  
 R 9  and R 9′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 OC═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 wherein said condition or disorder is selected from the group consisting of proliferate diseases, cancers, benign prostate hypertrophia, adenomas and neoplasies of the prostate, benign or malignant tumor cells containing the androgen receptor, heart disease, angiogenic conditions or disorders, hirsutism, acne, hyperpilosity, inflammation, immune modulation, seborrhea, endometriosis, polycystic ovary syndrome, androgenic alopecia, hypogonadism, osteoporosis, suppressing spermatogenisis, libido, cachexia, anorexia, inhibition of muscular atrophy in ambulatory patients, androgen supplementation for age related decreased testosterone levels in men, cancers expressing the estrogen receptor, prostate cancer, breast cancer, endometrial cancer, hot flushes, vaginal dryness, menopause, amennoreahea, dysmennoreahea, contraception, pregnancy termination, cancers containing the progesterone receptor, endometriosis, cachexia, menopause, cyclesynchrony, meniginoma, fibroids, labor induction, autoimmune diseases, Alzheimer's disease, psychotic disorders, drug dependence, non-insulin dependent Diabetes Mellitus, dopamine receptor mediated disorders, congestive heart failure, disregulation of cholesterol homeostasis, and attenuating the metabolism of a pharmaceutical agent.  
 
     
     
         24 . A method for preparation of a compound of the following formula XVI, or salt thereof:  
       where  
       
         
           
           
               
               
           
         
         G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;  
         Z 1  is O, S, NH, or NR 6 ;  
         Z 2  is O, S, NH, or NR 6 ;  
         A 1  is CR 7  or N;  
         A 2  is CR 7  or N;  
         Y′ is J—J′J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is O, S, S═O, SO 2 , NH, NR 7 , OP═OOR 2 , OC═O, NR 1 C═O, OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N, and J″ is (CR 7 R 7′ )n and n=0-3;  
         Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
         Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
         L is a bond, (CR 7 R 7′ )n, NH, NR 5  or NR 5 (CR 7 R 7′ )n, where n=0-3;  
         R 1  and R 1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
         R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
         R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 OR 1 , SO 2 R 1  or SO 2 NR 1 R 1′ ;  
         R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
         R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ; and  
         R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, hydroxylamine, hydroxylamide, amino, NHR 4 , NR 2 R 5 , NOR 1 , thiol, alkylthio or substituted alkylthio, R 1 C═O, R 1 (C═O)O, R 1 OC═O, R 1 NHC═O, SO 2 R 1 , SOR 1 , PO 3 R 1 R 1′ , R 1 R 1′ NC═O, C═OSR 1 , SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
         comprising the steps of contacting a compound of the following formula XV, or salt thereof:  
         
           
             
             
                 
                 
             
           
         
         where the symbols are as defined above;  
         with an enzyme or microorganism capable of catalyzing the hydroxylation of said compound XV to said compound XVI, and effecting said hydroxylation.  
       
     
     
         25 . A method for preparation of a compound of the following formula XVIII, or salt thereof:  
       
         
           
           
               
               
           
         
       
       where 
 G is an aryl or heterocyclo group, where said group is mono- or polycyclic, and which is optionally substituted at one or more positions;  
 Z 1  is O, S, NH, or NR 6 ;  
 Z 2  is O, S, NH, or NR 6 ;  
 A 1  is CR 7  or N;  
 A 2  is CR 7  or N;  
 Y′ is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is O, S, S═O, SO 2 , NH, NR 7 , OP═OOR 2 , OC═O, NR 1 C═O, OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N, and J″ is (CR 7 R 7′ )n and n=0-3;  
 Q 1  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 Q 2  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocycloalkyl or substituted heterocycloalkyl, arylalkyl or substituted arylalkyl, alkynyl or substituted alkynyl, aryl or substituted aryl, heterocyclo or substituted heterocyclo, halo, CN, R 1 OC═O, R 4 C═O, R 5 R 6 NC═O, HOCR 7 R 7′ , nitro, R 1 OCH 2 , R 1 O, NH 2 , C═OSR 1 , SO 2 R 1  or NR 4 R 5 ;  
 L is a bond, (CR 7 R 7′ )n, NH, NR 5  or NR 5 (CR 7 R 7′ )n, where n=0-3;  
 R 1  and R 1′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkyalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 2  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl;  
 R 4  is H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 OR 1 , SO 2 R 1  or SO 2 NR 1 R 1′ ;  
 R 5  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 R 6  is alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, CN, OH, OR 1 , R 1 C═O, R 1 NHC═O, SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ; and  
 R 7  and R 7′  are each independently H, alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, cycloalkylalkyl or substituted cycloalkylalkyl, cycloalkenylalkyl or substituted cycloalkenylalkyl, heterocycloalkyl or substituted heterocycloalkyl, aryl or substituted aryl, arylalkyl or substituted arylalkyl, halo, CN, OR 4 , nitro, hydroxylamine, hydroxylamide, amino, NHR 4 , NR 2 R 5 , NOR 1 , thiol, alkylthio or substituted alkylthio, R 1 C═O, R 1 (C═O)O, R 1 OC═O, R 1 NHC═O, SO 2 R 1 , SOR 1 , PO 3 R 1 R 1′ , R 1 R 1′ NC═O, C═OSR 1 , SO 2 R 1 , SO 2 OR 1 , or SO 2 NR 1 R 1′ ;  
 comprising the steps of contacting a compound of the following formula XVII, or salt thereof:  
                     
 where the symbols are as defined above;  
 with an enzyme or microorganism capable of catalyzing the opening of the epoxide ring of compound XVII to form the diol of said compound XVIII, and effecting said ring opening and diol formation.  
 
     
     
         26 . A compound of the following formula Ib:  
       
         
           
           
               
               
           
         
       
       where G, Z 1 , Z 2 , Q 1  and Q 2  are as defined in  claim 1;  
 Y′ is J—J′—J″ where J is (CR 7 R 7′ )n and n=0-3, J′ is a bond or O, S, S═O, SO 2 , NH, NR 7 , CR 7 R 7′ , R 2 P═O, R 2 P═S, R 2 OP═O, R 2 NHP═O, OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, N═N, cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, or heterocyclo or substituted heterocyclo, and J″ is (CR 7 R 7′ )n and n=0-3, where Y is not a bond; and  
 W′ is CR 7 R 7′ —CR 7 R 7′ , CR 7 R 7′ —C═O, NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , cycloalkyl or substituted cycloalkyl, cycloalkenyl or substituted cycloalkenyl, heterocyclo or substituted heterocyclo, or aryl or substituted aryl, wherein, when W′ is not NR 9 —CR 7 R 7′ , N═CR 8 , N═N, NR 9 —NR 9′ , or heterocyclo or substituted heterocyclo, then J′ must be O, S, S═O, SO 2 , NH, NR 7 , OP═OOR 2 , OP═ONHR 2 , OSO 2 , NHNH, NHNR 6 , NR 6 NH, or N═N; or alternatively,  
 Y′ is CR 7 R 7′ —C═O and W′ is NR 9 —CR 7 R 7′ ;  
 L is a bond; and  
 A 1  and A 2  are as defined above with the proviso that, when Y′=O and W′=—CH 2 —CH 2 —, then at least one of A 1  or A 2  is not CH;  
 with the further provisos (2), (3), (6), (7) and (8) of  claim 1;   
 or a pharmaceutically acceptable salt, solvate, prodrug or stereoisomer thereof.