Fused heterocyclic 11-beta-hydroxysteroid dehydrogenase type 1 inhibitors

A compound of formula (I) W-L-Z enantiomers, diastereomers or salts thereof wherein:

• W is —C(═O)R6, —C(OH)R6(R6), —C(═O)OR6, —C(═O)NR6R6, halogen, —OH, alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, wherein the alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl may be optionally substituted with R1, R1a, R1b, R1c and R1d;
• R1, R1a, R1b, R1c and R1d are independently hydrogen, halogen, —OH, —CN, —NO2, —CO2R6, —CONR6R6, —SO2NR6R6, —SOR6, —SO2R6, —NR6SO2R6, —NR6CO2R6, —OCONR6R6, tetrazolyl, alkyl, haloalkyl, cycloalkyl, alkoxy, aryloxy, alkenyl, haloalkoxy, alkylthio, arylthio, arylsulfonyl, alkylamino, aminoalkyl, arylamino, heteroarylamino, aryl, heteroaryl or heterocyclyl, wherein the tetrazolyl, alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R78, R2b, and R7c;
• or alternatively any two R1, R1a, R1b, R1c and R1d can be taken together to form a fused cycloalkyl, aryl, heteroaryl, heterocyclyl ring or spiro heterocyclyl ring;
• L is a bond, O, S, SO, SO2, C(═O), alkenyl, cycloalkyl, NR5, CR2R2a, CR2R6, CR2R2aCR2bR2c, SO2NR6, OCR2R2a, OCR2R2aCR2bR2c, CR2R2aO, CR2bR2cCR2R2aO, N(R5)CR2R2a, CR2R2aN(R5), SCR2R2a, CR2R2aS, CR2R2aSO, CR2R2aSO2, SOCR2R2a, SO2CR2R2a, CR2R2aOCR2bR2c, CR2R2aSCR2bR2c, CR2R2aSO2CR2bR2c, SO2NR6CR2aR2b, COCR2R2a, CR2R2aCO, CONR6CR2aR2b, CR2R2aCR2bR2cS, CR2R2,CR2bR2cSO, CR2R2aCR2bR2cSO2, provided that W is not halogen or —OH when L is O, S, SO, SO2, C(═O) or NR5;
• R2, R2a, R2b and R2c are independently hydrogen, halogen, —OH, alkyl, cycloalkyl, aryl, or haloalkyl;
• or alternatively any two R2, R2a, R2b, and R2c can be taken together to which the atom they are attached to form a cycloalkyl, halogen substituted cycloalkyl or heterocyclyl ring;
• Z is selected from the following bicyclic heteroaryl groups:
• R3 is hydrogen, halogen, —OH, —CN, —NO2, —CO2R6, —CONR6R6, —SO2NR6R6, —SOR6, —SO2R6, —NR6SO2R6, —NR6CO2R6, —OCONR6R6, tetrazolyl, alkyl, haloalkyl, cycloalkyl, alkoxy, aryloxy, alkenyl, haloalkoxy, alkylthio, arylthio, arylsulfonyl, alkylamino, arylamino, heteroarylamino, aryl, heteroaryl or heterocyclyl, wherein the tetrazolyl, alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• R3a is hydrogen, halogen, —OH, —CN, —NO2, —CO2R6, —CONR6R6, —SO2NR6R6, —SOR6, —SO2R6, —NR6SO2R6, —NR6CO2R6, —OCONR6R6, tetrazolyl, alkyl, haloalkyl, cycloalkyl, alkoxy, aryloxy, alkenyl, haloalkoxy, alkylthio, arylthio, arylsulfonyl, alkylamino, aminoalkyl, arylamino, heteroarylamino, aryl, heteroaryl or heterocyclyl, wherein the tetrazolyl, alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• or alternatively any R3 and R3a can be taken together to form a fused cycloalkyl, aryl, heteroaryl or heterocyclyl ring, which may be optionally substituted with R1, R1a, R1b, R1c and R1d;
• or alternatively one of R3 or R3a can be taken together with W-L to form a fused cycloalkyl, aryl, heteroaryl or heterocyclyl ring, which may be optionally substituted with R1, R1a, R1b, R1c and R1d;
• R4 is cycloalkyl, which may be optionally substituted with one or more substituents selected from halogen, —OH, —OR6, —SR6, —OCOR6, —CN, —NR6COR6, —NR6SO2R6, —COR6, —CO2R6, —CO2H, —OCONR6R6, —CONR6R6, —NR6CO2R6, —SO2R6, alkyl, cycloalkyl, Spiro cycloalkyl, Spiro heterocycloalkyl, aryl, amino, heterocyclyl or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, Spiro cycloalkyl, spiro heterocycloalkyl, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• provided that R4 is not cycloalkyl when (i) W is aryl, cycloalkyl, heteroaryl or heterocyclyl and (ii) Z is formula (d);
• or
• R4 is heterocyclyl, which may be optionally substituted with one or more substituents selected from halogen, —OR6, —SR6, —OCOR5, —CN, —NR6COR6, —NR6SO2R6, —COR6, —CO2R6, —CO2H, —OCONR6R5, —CONR6R6, —NR6CO2R6, —SO2R6, alkyl, cycloalkyl, Spiro cycloalkyl, spiro heterocycloalkyl, aryl, amino, heterocyclyl or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, spiro cycloalkyl, Spiro heterocycloalkyl, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• or
• R4 is alkyl, which may be optionally substituted with one or more substituents selected from halogen, —OH, —OR6, —SR6, —OCOR6, —CN, —NR6COR6, —NR6SO2R6, —COR6, —CO2R6, —CO2H, —OCONR6R6, —CONR6R6, —NR6CO2R6, —SO2R6, alkyl, cycloalkyl, Spiro cycloalkyl, Spiro heterocycloalkyl, aryl, amino, heterocyclyl or heteroaryl, wherein the alkyl, alkoxy, cycloalkyl, Spiro cycloalkyl, Spiro heterocycloalkyl, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• R5, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, haloalkyl, COR6, CO2R5, SO2NR6R6, or SO2R6;
• R6, at each occurrence, is independently H, alkyl, cycloalkyl, aryl or heteroaryl, all of which may be optionally substituted with R7, R7a, R7b, and R7c;
• or
• two R6's may be taken together with the atom to which they are attached to form a 3- to 7-membered cycloalkyl or heterocyclyl ring, which may be optionally substituted with R7, R7a, R7b and R7c;
• R7, R7a, R7b, and R7c, at each occurrence, are independently halo, alkyl, haloalkyl, alkoxy, aryl, aryloxy, arylaryl, arylalkyl, arylalkyloxy, alkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, amino, —OH, hydroxyalkyl, acyl, heteroaryl, heteroaryloxy, heteroarylalkyl, heteroarylalkoxy, aryloxyalkyl, alkylthio, arylalkylthio, aryloxyaryl, alkylamido, alkanoylamino, arylcarbonylamino, —NO2, —CN, —CO2H, tetrazolyl or thiol, wherein the alkyl, alkoxy, aryl, aryloxy, arylaryl, arylalkyl, arylalkyloxy, alkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, heteroaryl, heteroaryloxy, heteroarylalkyl, heteroarylalkoxy, aryloxyalkyl, alkylthio, arylalkylthio, aryloxyaryl, alkylamido, alkanoylamino, arylcarbonylamino or tetrazolyl may be optionally substituted with R8, R8a, R8b, and R8c;
• and
• R8, R8a, R8b, and R8c, at each occurrence, are independently halo, alkyl, haloalkyl, alkoxy, aryl, aryloxy, arylaryl, arylalkyl, arylalkyloxy, alkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, amino, —OH, hydroxyalkyl, acyl, heteroaryl, heteroaryloxy, heteroarylalkyl, heteroarylalkoxy, aryloxyalkyl, alkylthio, arylalkylthio, aryloxyaryl, alkylamido, alkanoylamino, arylcarbonylamino, —NO2, —CN, —CO2H, tetrazolyl or thiol.