Triazolopyridine 11-beta hydroxysteroid dehydrogenase type I inhibitors

A compound of formula I

• enantiomers, diastereomers, or salts thereof wherein:
• Q is L, Laa or Lee;
• X is C and Y is N;
• G is R4, R4aa or R4ee;
• L is -alkenyl-(W1)n, -cycloalkyl-(W1)n or -alkyl-(W2)n;
• Laa is -alkenyl-(W1)n or -alkyl-(W2aa)n;
• Lee is -alkenyl-(W1ee)n, -cycloalkyl-(W1)n or -alkyl-(W2ee)n;
• n is 1 to 3;
• W1, at each occurrence, is independently halogen, —OH, —CN, —CO2R6, —CONR8R8a, —OCONR8R8a, —SO2NR8R8a, —SOR6, —SO2R6, —NR9SO2R9a, —NR9CO2R9a, —NR9COR9a, alkyl, cycloalkyl, haloalkyl, alkoxy, aryloxy, haloalkoxy, alkylthio, arylthio, arylsulfonyl, alkylamino, amino, aminoalkyl, arylamino or heteroarylamino;
• W1ee is independently halogen, —OH, —CN, —CO2R6, —CONR8R8a, —OCONR8R8a, —SO2NR8R8a, —SOR6, —SO2R6, —NR9SO2R9a, —NR9CO2R9a, —NR9COR9a, cycloalkyl, alkyl, haloalkyl, alkoxy, aryloxy, haloalkoxy, alkylthio, arylthio, arylsulfonyl, alkylamino, amino, aminoalkyl, arylamino or heteroarylamino;
• W2 is independently —OH, —CO2H, —CO2R6, —CONR8R8a, —OCOR6, —OCONR8R8a, —SO2NR8R8a, —SO-alkyl, —SO2-alkyl, —NR9SO2R9a, —NR9CO2R9a, —NR9COR9a, cycloalkyl, alkyl, haloalkyl, alkoxy, alkenyl, haloalkoxy, alkylthio, alkylamino, amino or aminoalkyl;
• W2aa is independently —OH, —CO2H, —CO2R6, —CONR8R8a, —OCOR6, —OCONR8R8a, —SO2NR8R8a, —SO-alkyl, —SO2-alkyl, —NR9SO2R9a, —NR9CO2R9a, —NR9COR9a, —OR9bOR9bSi(R9b)3, cycloalkyl, alkyl, haloalkyl, alkoxy, alkenyl, haloalkoxy, alkylthio, alkylamino, amino or aminoalkyl;
• W2ee is independently —OH, —CO2H, —CO2R6, —CONR8R8a, —OCOR6, —OCONR8R8a, —SO2NR8R8a, —SO-alkyl, —SO2-alkyl, —NR9SO2R9a, —NR9CO2R9a, —NR9COR9a, cycloalkyl, alkyl, haloalkyl, alkenyl, haloalkoxy, alkylthio, amino, aminoalkyl, aryl, heteroaryl or heterocyclyl, wherein the aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• provided that W2aa or W2ee are not only alkyl;
• R3, R3a and R3b are independently hydrogen, halogen, —OH, —NO2, —CO2R8a, —CONR8R8a, —SO2NR8R8a, —SOR8a, —SO2R8a, —NR8SO2R6, —NR8CO2R6, alkyl, haloalkyl, cycloalkyl, alkoxy, aryloxy, alkenyl, haloalkoxy, alkylthio, arylthio, arylsulfonyl, alkylamino, aminoalkyl, arylamino, heteroarylamino, aryl, heteroaryl or heterocyclyl, wherein the aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• R4 is alkyl, cycloalkyl or heterocyclyl, all of which may be optionally substituted with one or more substituents selected from halogen, —OH, —OR6, —SR6, —OCOR6, —CN, —NR5COR6, —NR5SO2R6, —COR6, —CO2R6, —CO2H, —OCONR8R8a, —CONR8R8a, —NR5CO2R6, —SO2R6, alkyl, alkoxy, aryl, amino, heterocyclyl or heteroaryl, wherein the alkyl, alkoxy, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• R4aa is cycloalkyl, which may be optionally substituted with one or more substituents selected from halogen, —OH, —OR6, —SR6, —OCOR6, —CN, —NR5COR6, —NR5SO2R6, —COR6, —CO2R6, —CO2H, —OCONR8R8a, —CONR8R8a, —NR5CO2R6, —SO2R6, alkyl, alkoxy, aryl, amino, heterocyclyl or heteroaryl, wherein the alkyl, alkoxy, aryl, heteroaryl or heterocyclyl may be optionally substituted with R7, R7a, R7b, and R7c;
• R4ee is alkyl or cycloalkyl, both of which may be optionally substituted with one or more substituents selected from halogen, —OH, —OR6, —SR6, —OCOR6, —CN, —NR5COR6, —NR5SO2R6, —COR6, —CO2R6, —CO2H, —OCONR8R8a, —CONR8R8a, —NR5CO2R6, —SO2R6, alkyl, alkoxy, aryl, amino, heterocyclyl or heteroaryl, wherein the alkyl, alkoxy, 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, COR8a, CO2R8a, SO2NR8R8a, or SO2R8a;
• R6, at each occurrence, is independently alkyl, cycloalkyl, aryl or heteroaryl, all of which may be optionally substituted with R7, R7a, R7b, and R7c;
• R7, R7a, R7b, and R7c, at each occurrence, are independently halo, alkyl, haloalkyl, cyanoalkyl, alkoxy, haloalkoxy, aryl, aryloxy, arylaryl, arylalkyl, arylalkyloxy, alkenyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkyloxy, amino, —OH, —CO2R8, —CONR8R8a, hydroxyalkyl, acyl, heteroaryl, heteroaryloxy, heteroarylalkyl, heteroarylalkoxy, aryloxyalkyl, alkylthio, arylalkylthio, aryloxyaryl, alkylamido, alkanoylamino, arylcarbonylamino, alkylsilicaalkyloxy, —SO2R9b—NO2, —CN or thiol, wherein the aryl or heteroaryl may be optionally substituted with R10, R10a, R10b, and R10c;
• R8 and R8a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl or heterocyclyl, all of which may be optionally substituted with R10, R10a, R10b, and R10c;
• or alternatively R8 and R8a can be taken together with the nitrogen to which they are attached to form a heterocyclyl ring containing 1, 2, 3, or 4 heteroatoms independently selected from the group consisting of N, NH, O and S, which may be optionally substituted with R10, R10a, R10b, and R10c;
• R9 and R9a, at each occurrence, is independently hydrogen, alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl or heterocyclyl, all of which may be optionally substituted with R10, R10a, R10b, and R10c;
• R9b, at each occurrence, is independently alkyl, cycloalkyl, aryl or heteroaryl, all of which may be optionally substituted with R10, R10a, R10b, and R10c;
• and
• R10, R10a, R10b, and R10c, at each occurrence, are independently halo, alkyl, haloalkyl, cyanoalkyl, 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 or thiol;
• provided that:
• (a) W1, W1ee, W2, or W2aa is not cycloalkyl when n is 1 and R4, R4aa or R4ee are cycloalkyl;
• (b) W2ee is not cycloalkyl, aryl, heteroaryl or heterocyclyl when n is 1 and R4ee is cycloalkyl;
• (c) R7, R7a, R7b, and R7c must be substituted with at least one R10, R10a, R10b, or R10c when (i) Lee is cycloalkyl, (ii) R4ee is cycloalkyl substituted with aryl, heterocyclyl or heteroaryl, (iii) the aryl, heteroaryl or heterocyclyl is substituted with R7, R7a, R7b, or R7c;
• and (iv) R7, R7a, R7b, and R7c is aryl, heteroaryl or heterocyclyl;
• (d) Laa and Lee are not C1-3alkyl when R4aa or R4ee are substituted with an optionally substituted aryl moiety;
• and
• (e) W2ee is not alkyl, haloalkyl or aryl when R4ee is alkyl.