Pyrazolotriazines as CRF antagonists

A compound of formula I:

• 46
• or a stereoisomer or pharmaceutically acceptable salt thereof, wherein:
• A equals N or CR5;
• B equals CR4;
• provided that A can not be CR5 and B can not be CR4 to form a pyrazolopyrimidine;
• and wherein,
• R1 is independently selected from the group consisting of
• H,
• halogen,
• CN,
• C1-6 alkyl,
• C2-10 alkenyl,
• C2-10 alkynyl,
• C3-6 cycloalkyl,
• C1-6 alkyloxy,
• C1-6 alkylS (O)n,
• —NR1aR1B wherein R1a and R1b are independently selected from H, C1-4 alkyl, C3-8 cycloalkyl, —C(O)C1-4alkyl,
• C1-6 alkylNR1aR1b,
• NR1aCOR1b,
• —C(O)NR1aR1b,
• —O—C(O)C1-4alkyl,
• —XR1c wherein R1c is selected from H or —C1-4 alkylaryl;
• X is selected from 0 or S(O)n,
• wherein R1 is substituted with 0-6 substituents selected from halogen, C1-4 alkyl, C3-8 cycloalkyl, C1-6 alkyloxy, C1-4 haloalkyl, C1-4alkylamino, C2-8 dialkylamino, C1-4alkyloxy, C1-4 alkylthio, C1-4 alkylsulfinyl or C1-4 alkylsulfonyl;
• R2 is selected from the group consisting of OR7, SH, NR6R7, C(OH)R6R6a, C(OR7)R6R6a, S(O)nR13, COR7, CO2R7, CHR6(OR7) R6a, OC(O)R13, NO, NO2, NR6C(O)R7, N(COR7)2, NR8CONR6R7 or NR6CO2R7;
• or R2 is selected from:
• C1-10 alkyl,
• C2-10 alkenyl,
• C2-10 alkynyl,
• C3-8 cycloalkyl,
• C3-6 cycloalkyl C1-6 alkyl,
• C1-10 alkyloxy,
• C1-10 alkyloxyC1-10 alkyl,
• —SO2-C1-10alkyl
• —SO2R2a wherein R2a is aryl,
• —SO2R2b wherein R2b is heteroaryl,
• —NR2CR2D wherein R2c and R2d are independently selected from H, C1-8 alkyl, S(O)nC1-4alkyl, C(O)NR2cR2d, CO2C1-4alkyl, C3-8 cycloalkyl, C1-6 alkyloxyC1-6 alkyl,
• —C(O)C1-4alkyl or R2c and R2d may join to form a heterocyclic ring having 0-3 heteroatoms selected from O, N or S,
• —(O)—L wherein L is selected from H, NR2cR2d, and C1-6 alkyl O(CH2)mOR wherein R is
• C1-3 alkyl, O(CH2)m—NR2cR2d,OH, C(O)OC1-6alkyl, or aryl or heteroaryl wherein m is 1-4;
• or
• —OC(O)—M wherein M is selected from C1-4 alkyl, C1-4 haloalkyl, C2-8 alkoxyalkyl,
• C3-6 cycloalkyl, C4-12 cycloalkylalkyl, aryl, C1-6 alkylaryl, heteroaryl, and C1-6 alkylheteroaryl;
• n is 0, 1 or 2;
• and wherein
• R2 is substituted with 0-3 substituents independently selected from R′, R″, R′″ wherein R′, R″ and R′″ are independently selected from C1-6 alkyl, C3-7 cycloalkyl, hydroxyC1-6 alkyl, C1-6 alkyloxyC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyloxy, and hydroxy, or
• R2 is substituted with 0-3 substituents independently selected from:
• halogen,
• —CN,
• —S(O)nR2e wherein R2e is selected from C1-4alkyl, C1-4 haloalkyl, C1-4 alkyloxy C1-4 alkyl, and C3-6 cycloalkyl;
• —COR2f wherein R2f is selected from H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkyloxy C1-4 alkyl,
• C3-6 cycloalkyl, and C3-6 cycloalkylC1-4 alkyl;
• —CO2R2f,
• —NR2gCOR2f wherein R2g is selected from H, C1-6 alkyl, C3-7 cycloalkyl, and
• C3-6 cycloalkylC1-6 alkyl;
• —N(COR2f)2,
• —NR2gCONR2fR2h, wherein R2h is selected from H, C1-6 alkyl, C1-4 haloalkyl,
• C1-4 alkoxy C1-4 alkyl, C3-6 cycloalkyl and C3-6 cycloalkylC1-6 alkyl;
• —NR2gCO2R2e,
• CONR2gR2h,
• 1-morpholinyl,
• 1-piperidinyl,
• 1-piperazinyl, and
• C3-8 cycloalkyl wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from —O—, —S(O)n—, —NR2g—, —NCO2R2e, —NCOR2e, and —NSO2R2e;
• and wherein N4 in 1-piperazinyl is substituted with 0-1 substituents selected from R2g, CO2R2e, COR2e and SO2R2e;
• or
• the group R2i, R2j, R2k, C1-6alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, —OR2g, —NR2gR2h, —C1-6 alkyl-OR2g, and C3-8 cycloalkyl which is substituted with 0-1 R21 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by —O—, wherein
• R2i is selected from aryl wherein aryl is selected from phenyl, naphthyl, indanyl and indenyl, each R2i being substituted with 0-1 OR2m and 0-5 substituents independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, —SH, —S(O)nR2n, —COR2m, —OC(O)R2n, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2n, —NR2oR2p and —CONR2oR2p;
• R2j is selected from heteroaryl wherein heteroaryl is selected from pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-s-oxide, 2,3-dihydro-benzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, OR2m, —SH, —S(O)nR2h, —COR2m, —OC(O)R2h, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2h, —NR2oR2p and —CONR2oR2p and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R2g, CO2R2e, COR2e and SO2R2e;
• R2k is heterocyclyl which is a saturated or partially saturated heteroaryl as defined for R2j, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, —OR2m, —SH, —S(O)nR2h, —COR2m, —OC(O)R2h, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, NR2gCO2R2h, —NR2oR2p and —CONR2oR2p7 and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R2f, CO2R2e, COR2e and SO2R2e;
• wherein
• R21 is H, C1-4 alkyl, C3-6 cycloalky-C1-4 alkyl or C3-8 cycloalkyl;
• R2m is H, C1-6 alkyl, C3-6 cycloalkyl C1-6 alkyl, C12 alkyloxy C1-2 alkyl, C1-4 haloalkyl, R2qS(O)n—C1-4 alkyl or R2rR2sN—C2-4 alkyl;
• R2n is H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkyloxy C1-2 alkyl, or
• C1-4 haloalkyl;
• R2o and R2p are independently selected at each occurrence from H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl C1-6 alkyl and C1-4 haloalkyl;
• R2q is selected from C1-6 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl), heteroaryl and heteroaryl (C1-4 alkyl)- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino;
• R2rR2s taken together with the N form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl wherein N4 in 1-piperiazinyl is substituted with 0-1 substituents selected from the group R2t, CO2R2q, COR2q and SO2R2q;
• R2t is selected from H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy —C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl (C1-4 alkyl)-, heteroaryl and heteroaryl (C1-4 alkyl);
• R3 is selected from an aryl or heteroaryl group attached through an unsaturated carbon atom;
• aryl is selected from phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from C1-6 alkyl, C3-6 cycloalkyl, methylenedioxy, C1-4 alkyloxy-C1-4 alkyloxy, —OR2m, Br, Cl, F, I, C1-4 haloalkyl, —CN, —NO2, —SH, —S(O)nR2n, —COR2m, —CO2R2m, —OC(O)R2n, NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2h, —NR2oR2p and CONR2oR2p;
• heteroaryl is selected from the group pyridyl, pyrimidyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzo-furanyl, 2,3-dihydrobenzothienyl, 2,3-dihydro-benzothienyl-S-oxide, 2,3-dihydrobenzothienyl-s-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted at 0-4 carbon atoms with a substituent independently selected at each occurrence from C1-6 alkyl, C3-6 cycloalkyl, Br, F, I, C1-4 haloalkyl, —CN, NR2gR2h, nitro, —OR2m, —SH, —S(O)nR2n, COR2m, —CO2R2m, —OC(O)R2n, —NR2gCOR2m, —N(COR2m)2, and —NR2gCONR2oR2p and each heteroaryl being substituted at any nitrogen atom with 0-1 substituents selected from the group R2g, CO2R3a, COR3a and SO2R3a wherein,
• R3a is selected from the group C1-6 alkyl, C1-4 cycloalkyl-C1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
• R4 and R5 are independently selected at each occurrence from H, Br, Cl, F, I, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C1-6 alkyloxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, amino, C1-4 alkylamino, (C1-4 alkyl)2 amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group consisting of C1-7 alkyl, C3-8 cycloalkyl, Br, Cl, F, I, —C(O)H, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-6 alkylamino and (C1-4 alkyl)2 amino and wherein R4 and R5 non-phenyl groups may be substituted with 0-5 substituents selected from OH, halogen, —C(O)H, —OC1-6-alkyl and C1-6 haloalkyl, C1-6 alkyl, C3-7 c-alkyl, C1-6 alkyl(OH)nCO2R wherein R is H or C1-6 alkyl, C1-6 alkyl(OH)n, wherein n is 0-3 or R4 and R5 may join together to form a C3-6 alkylene chain;
• R6, R6a and R7 are independently selected from:
• H, C1-10 alkyl, C3-10 cycloalkyl, C3-10 alkenyl, C3-10 alkynyl, C1-10 haloalkyl, C2-8 alkoxyalkyl, C4-12 cycloalkylalkyl, C5-10 cycloalkenyl, and C6-14 cycloalkenylalkyl;
• and
• R6, R6a and R7 are substituted with 0-6 substituents independently selected from halogen, C1-4 alkyl, C3-8 cycloalkyl, C1-6 alkyloxy, and C4 haloalkyl.

A compound of formula Ib

• 47
• wherein R1 is independently selected from the group consisting of
• H,
• halogen,
• CN,
• C1-6 alkyl,
• C2-10 alkenyl,
• C2-10 alkynyl,
• C3-6 cycloalkyl,
• C1-6 alkyloxy,
• C1-6 alkylS(O)n,
• —NR1aR1b wherein R1a and R1b are independently selected from H, C1-4 alkyl, C3-8 cycloalkyl,
• —C(O)C1-4alkyl,
• C1-6 alkylNR1aR1b,
• NR1aCOR1b,
• —C(O)NR1aR1b,
• —O—C(O)C1-4alkyl,
• —XR1c wherein R1c is selected from H or —C1-4 alkylaryl;
• X is selected from 0 or S(O)n,
• wherein R1 is substituted with 0-6 substituents selected from halogen, C1-4 alkyl, C3-8 cycloalkyl, C1-6 alkyloxy, C1-4 haloalkyl, C1-4alkylamino, C2-8 dialkylamino, C1-4 alkylthio, C1-4 alkylsulfinyl or C1-4 alkylsulfonyl;
• R2 is selected from the group consisting of H, OR7, SH, NR6R7, C(OH)R6R6a, C(OR7)R6R6a, S(O)nR13, COR7, CO2R7, CHR6(OR7)R6a, OC(O)R13, NO, NO2, NR6C(O)R7, N(COR7)2, NR8CONR6R7, NR6CO2R7;
• or
• C1-10 alkyl,
• C2-10 alkenyl,
• C2-10 alkynyl,
• 3-8 cycloalkyl,
• C3-6 cycloalkyl C1-6 alkyl,
• C1-10 alkyloxy,
• 1-10 alkyloxyC1 alkyl,
• —SO2—C1-10 alkyl
• —SO2R2a wherein R2a is aryl,
• —SO2R2b wherein R2b is heteroaryl,
• —NR2cR2dwherein R2c and R2d are independently selected from H, C1-8 alkyl, S(O)nC1-4alkyl, C(O)NR2cR2d, CO2C1-4alkyl, C3-8 cycloalkyl, C1-6 alkyloxyC1-6 alkyl, or —C(O)C1-4alkyl,
• —halogen,
• —CN,
• —C(O)—L wherein L is selected from H, NR2cR2d, C1-6 alkyl or OC1-4 alkyl, O(CH2)mOR wherein R is C1-3 alkyl, O(CH2)m—NR2cR2d,OH, C(O)OC1-6alkyl or aryl or heteroaryl
• wherein m is 1-4;
• —OC(O)—M wherein M is selected from C1-4 alkyl, C1-4 haloalkyl, C2-8 alkoxyalkyl,
• C3-6cycloalkyl, C4-12 cycloalkylalkyl, aryl, C1-6 alkylaryl, heteroaryl,
• C1-6 alkylheteroaryl;
• n is 0, 1 or 2;
• and wherein
• R2 is substituted with 0-3 substituents independently selected from R′, R″, R′″ wherein R′, R″ and R′″ are independently selected from C1-6 alkyl, C3-7 cycloalkyl, hydroxyC1-6 alkyl, C1-6 alkyloxyC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyloxy, hydroxy, or
• R2 is substituted with 0-3 substituents independently selected from:
• halogen,
• —CN,
• —S(O)nR2e wherein R2e is selected from C1-4 alkyl, C1-4 haloalkyl,C1-4 alkyloxy C1-4 alkyl,
• C3-6 cycloalkyl;
• —COR2f wherein R2f is selected from H, C1-4alkyl, C1-4 haloalkyl, C1-4 alkyloxy C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkylC1-4 alkyl;
• —CO2R2f,
• —NR2gCOR2f wherein R2g is selected from H, C1-6 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl C1-6 alkyl;
• —N(COR2f)2,
• —NR2gCONR2fR2h, wherein R2h is selected from H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkoxy C1-4 alkyl, C3-6 cycloalkyl and C3-6 cycloalkylC1-6 alkyl;
• —NR2gCO2R2e,
• —CONR2gR2h,
• 1-morpholinyl,
• 1-piperidinyl,
• 1-piperazinyl, and
• C3-8 cycloalkyl wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from —O—, —S(O)n—, —NR2g—, —NCO2R2e, —NCOR2e, and —NSO2R2e;
• and wherein N4 in1-piperazinyl is substituted with 0-1 substituents selected from R2g, CO2R2e, COR2e and SO2R2e;
• or
• the group R2i, R2j, R2k, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, —OR2g, —NR2gR2h, —C1-6 alkyl-OR2g, and C3-8 cycloalkyl which is substituted with 0-1 R21 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by —O—, wherein R2i is selected from aryl wherein aryl is selected from phenyl, naphthyl, indanyl and indenyl, each R2i being substituted with 0-1 OR2m and 0-5 substituents independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, —SH, —S(O)nR2n, —COR2m, —OC(O)R2n, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2n, —NR2oR2p and —CONR2oR2p;
• R2j is selected from heteroaryl wherein heteroaryl is selected from pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-s-oxide, 2,3-dihydro-benzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, OR2m, —SH, —S(O)nR2h, —COR2m, —OC(O)R2h, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2h, —NR2oR2p and —CONR2oR2p and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R2g, CO2R2e, COR2e and SO2R2e;
• R2k is heterocyclyl which is a saturated or partially saturated heteroaryl as defined for R2j, each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4, haloalkyl, —CN, nitro, —OR2m, —SH, —S(O)nR2h, —COR2m, —OC(O)R2h, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR20CO2R2h, NR2gR2p and —CONR2oR2p and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R2f, CO2R2e, COR2e and SO2R2e;
• wherein
• R21 is H, C1-4 alkyl, C3-6 cycloalky-C1-4 alkyl or C3-8 cycloalkyl;
• R2m is H, C1-6 alkyl, C3-6 cycloalkyl C1-6 alkyl, C1-2 alkyloxy C1-2 alkyl, C1-4 haloalkyl, R2qS(O)n—C1-4 alkyl or R2rR2sN—C2-4 alkyl;
• R2n is H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkyloxy C1-2 alkyl, or C1-4 haloalkyl;
• R2o and R2p are independently selected at each occurrence from H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl C1-6 alkyl and C1-4 haloalkyl;
• R2q is selected from C1-6 alkyl, C1-4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl(C1-4 alkyl), heteroaryl and heteroaryl (C1-4 alkyl)- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino;
• R2rR2s taken together with the N form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl wherein N4 in 1-piperiazinyl is substituted with 0-1 substituents selected from the group R2t, CO2R2q,COR2q and SO2R2q;
• R2t is selected from H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy —C14 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl -C1-6 alkyl, aryl, aryl (C1-4 alkyl)-, heteroaryl and heteroaryl (C1-4 alkyl);
• R3 is an aryl or heteroaryl group attached through an unsaturated carbon atom;
• aryl is selected from phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from C1-6 alkyl, C3-6 cycloalkyl, methylenedioxy, C1-4 alkyloxy-C1-4 alkyloxy, —OR2m, Br, Cl, F, I, C1-4 haloalkyl, —CN, —NO2, —SH, —S(O)nR2n, —COR2n, —CO2R2m, —OC(O)R2n, —NR2gCOR2m, —N COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2h, —NR2oR2p and CONR2oR2p;
• heteroaryl is selected from the group pyridyl, pyrimidyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzo-furanyl, 2,3-dihydrobenzothienyl, 2,3-dihydro-benzothienyl-S-oxide, 2,3-dihydrobenzothienyl-s-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted at 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, F, I, C1-4 haloalkyl, —CN, NR2gR2h, nitro, —OR2m, —SH, —S(O)nR2n, COR2m, —CO2R2m, —OC(O)R2n, —NR2gCOR2m, —N(COR2m)2, —NRg2CONR2oR2p and each heteroaryl being substituted at any nitrogen atom with 0-1 substituents selected from the group R2g, CO2R3a, COR3a and SO2R3a wherein,
• R3a is selected from the group C1-6 alkyl, C1-4 cycloalkyl-C1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
• R4 is independently selected at each occurrence from H, Br, Cl, F, I, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C1-6 alkyloxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, amino, C1-4 alkylamino, (C1-4 alkyl)2 amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group consisting of C1-7 alkyl, C3-8 cycloalkyl, Br, Cl, F, I, —(O)H, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-6 alkylamino and (C1-4 alkyl)2 amino and wherein R4 non-phenyl groups may be substituted with 0-5 substituents selected from OH, halogen, —(O)H, —OC1-6-alkyl and C1-6 haloalkyl, C1-6 alkyl, C3-7 c-alkyl, C1-6 alkyl(OH)nCO2R wherein R is H or C1-6 alkyl, C1-6 alkyl (OH)n, wherein n is 0-3;
• R6, R6a and R7 are independently selected from:
• H, C1-10 alkyl, C3-10 cycloalkyl, C3-10 alkenyl, C3-10 alkynyl, C1-10 haloalkyl, C2-8 alkoxyalkyl, C4-12 cycloalkylalkyl, C5-10 cycloalkenyl, and C6-14 cycloalkenylalkyl;
• R6, R6a and R7 are substituted with 0-6 substituents independently selected from halogen, C1-4 alkyl, C3-8 cycloalkyl, C1-6 alkyloxy and C1-4 haloalkyl.

A compound of formula II

• 48
• wherein R1 is independently selected from the group consisting of
• H,
• halogen,
• CN,
• C1-6 alkyl,
• C2-10 alkenyl,
• C2-10 alkynyl,
• C3-6 cycloalkyl,
• C1-6 alkyloxy,
• C1-6 alkylS(O)n,
• —NR1aR1b wherein R1a and R1b are independently selected from
• H, C1-4 alkyl, C3-8 cycloalkyl,
• —C(O)C1-4alkyl,
• C1-6 alkylNR1aR1b,
• NR1aCOR1b,
• —C(O)NR1aR1b,
• —O—C(O C1-4alkyl,
• —XR1c wherein R1c is selected from H or —C1-4 alkylaryl;
• X is selected from O or S(O)n,
• wherein R1 is substituted with 0-6 substituents selected from halogen, C1-4 alkyl, C3-8 cycloalkyl, C1-6 alkyloxy, C1-4 haloalkyl, C1-4 alkylamino, C2-8 dialkylamino, C1-4 alkylthio, C1-4 alkylsulfinyl or C1-4 alkylsulfonyl;
• R2 is selected from the group consisting of H, OR7, SH, N6R7 C(OH)R6R6a, C(OR7)R6R6a, S(O)nR13, COR7, CO2R7, CHR6(OR7)R6a, OC(O)R13, NO, NO2, NR6C(O)R7, N(COR7)2, NR8CONR6R7, NR6CO2R7;
• or
• C1-10 alkyl,
• C2-10 alkenyl,
• C2-10 alkynyl,
• C3-8 cycloalkyl,
• C3-6 cycloalkyl C1-6 alkyl,
• C1-10 alkyloxy,
• C1-10 alkyloxyC1-10 alkyl,
• —SO2—C1-10alkyl
• —SO2R2a wherein R2a is aryl,
• —SO2R2b wherein R2b is heteroaryl,
• —NR2cR2d wherein R2c and R2d are independently selected from H, C1-8 alkyl, S(O)nC1-4alkyl, C(O)NR2cR2d, CO2C1-4alkyl, C3-8 cycloalkyl, C1-6 alkyloxyC1-6 alkyl, or —C(O)C1-4alkyl,
• -halogen,
• —CN,
• —(O)—L wherein L is selected from H, NR2cR2d, C1-6 alkyl or
• OC1-4 alkyl, O(CH2)mOR wherein R is C1-3 alkyl,
• O(CH2)m—NR2cR2d, OH, C(O)OC1-6alkyl or aryl or heteroaryl wherein m is 1-4;
• —OC(O)—M wherein M is selected from C1-4 alkyl, C1-4 haloalkyl, C2-8 alkoxyalkyl,
• C3-6cycloalkyl, C4-12 cycloalkylalkyl, aryl, C1-6 alkylaryl, heteroaryl,
• C1-6 alkylheteroaryl;
• n is 0, 1 or 2;
• and wherein
• R2 is substituted with 0-3 substituents independently selected from R′, R″, R′″ wherein R′, R″ and R′″ are independently selected from C1-6 alkyl, C3-7 cycloalkyl, hydroxyC1-6 alkyl, C1-6 alkyloxyC1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-6 alkyloxy, hydroxy, or
• R2 is substituted with 0-3 substituents independently selected from:
• halogen,
• —CN,
• —S(O)nR2e wherein R2e is selected from C1-4 alkyl, C1-4 haloalkyl, C1-4 alkyloxy C1-4 alkyl,
• C3-6 cycloalkyl;
• —COR2f wherein R2f is selected from H, C1-4alkyl, C1-4haloalkyl, C1-4 alkyloxy C1-4 alkyl, C3-6 cycloalkyl, and C3-6 cycloalkyl1-4 alkyl;
• —CO2R2f,
• —NR2gCOR2f wherein R2g is selected from H, C1-6 alkyl, C3-7 cycloalkyl, C3-6 cycloalkyl C1-6alkyl;
• —N(COR2f)2,
• —NR2gCONR2hR2, wherein R2h is selected from H, C1-6 alkyl, C1-4 haloalkyl, C1-4 alkoxy C1-4 alkyl, C3-6 cycloalkyl and C3-6 cycloalkylC1-6 alkyl;
• —NR2gCO2R2e,
• —CONR2gR2h,
• 1-morpholinyl,
• 1-piperidinyl,
• 1-piperazinyl, and
• C3-8 cycloalkyl wherein 0-1 carbon atoms in the C4-8 cycloalkyl is replaced by a group selected from —O—, —S(O)n—, —NR2g—, NCO2R2e, NCOR2e, and —NSO2R2e;
• and wherein N4 in1-piperazinyl is substituted with 0-1 substituents selected from R2g, CO2R2e, COR2e and SO2R2e;
• or
• the group R2i, R2j, R2k, C1-6 alkyl, C2-8 alkenyl, C2-8 alkynyl, Br, Cl, F, I, C1-4 haloalkyl, —OR2g, —NR2gR2h, —C1-6 alkyl-OR2g, and C3-8 cycloalkyl which is substituted with 0-1 R21 and in which 0-1 carbons of C4-8 cycloalkyl is replaced by —O—, wherein R2i is selected from aryl wherein aryl is selected from phenyl, naphthyl, indanyl and indenyl, each R2i being substituted with 0-1 OR2m and 0-5 substituents independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, —SH, —S(O)nR2n, —COR2m, —OC(O)R2n, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2oR2p and —CONR2oR2p;
• R2j is selected from heteroaryl wherein heteroaryl is selected from pyridyl, pyrimidinyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, pyrazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzofuranyl, 2,3-dihydrobenzothienyl, 2,3-dihydrobenzothienyl-s-oxide, 2,3-dihydro-benzothienyl-S-dioxide, indolinyl, benzoxazolin-2-onyl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted on 0-4 carbon atoms with a substituent independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, OR2m, —SH, —S(O)nR2h, —COR2m, —OC(O)R2h, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2h, —NR2oR2p and —CONR2oR2p and each heteroaryl being substituted on any nitrogen atom with 0-1 substituents selected from the group R2g, CO2R2e, COR2e and SO2R2e;
• R2k is heterocyclyl which is a saturated or partially saturated heteroaryl as defined for R2j;
• each heterocyclyl being substituted on 0-4 carbon atoms with a substituent independently selected from the group C1-6 alkyl, C3-6 cycloalkyl, Br, Cl, F, I, C1-4 haloalkyl, —CN, nitro, —OR2m, —SH, —S(O)nR2h, —CO(O)R2h, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, NR2gCO2R2h, —NR2oR2p and —CONR2oR2p and each heterocyclyl being substituted on any nitrogen atom with 0-1 substituents selected from the group R2f, CO2R2e, COR2e and SO2R2e;
• wherein
• R21 is H, C1-4 alkyl, C3-6 cycloalky-C1-4 alkyl or C3-8 cycloalkyl;
• R2m is H, C1-6 alkyl, C3-6 cycloalkyl C1-6 alkyl, C1-2alkyloxy C1-2 alkyl, C1-4 haloalkyl, R2qS(O)n—C1-4 alkyl or R2rR2sN—C2-4 alkyl;
• R2n is H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, C1-2 alkyloxy C1-2 alkyl,
• or C1-4 haloalkyl;
• R2o and R2p are independently selected at each occurrence from H, C1-6 alkyl, C3-10 cycloalkyl, C3-6 cycloalkyl C1-6 alkyl and C1-4 haloalkyl;
• R2q is selected from C1-6 alkyl, C4 haloalkyl, C1-4 alkoxy-C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C16 alkyl, aryl, aryl(C1-4 alkyl), heteroaryl and heteroaryl (C1-4 alkyl)- and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy C1-4 haloalkoxy, and dimethylamino;
• R2rR2s taken together with the N form 1-pyrrolidinyl, 1-morpholinyl, 1-piperidinyl or 1-piperazinyl wherein N4 in 1-piperiazinyl is substituted with 0-1 substituents selected from the group R2t, CO2R2q, COR2q and SO2R2q;
• R2t is selected from H, C1-4 alkyl, C1-4 haloalkyl, C1-4 alkoxy —C1-4 alkyl, C3-6 cycloalkyl, C3-6 cycloalkyl-C1-6 alkyl, aryl, aryl (C1-4 alkyl)-, heteroaryl and heteroaryl (C1-4 alkyl);
• R3 is an aryl or heteroaryl group attached through an unsaturated carbon atom;
• aryl is selected from phenyl, naphthyl, indanyl and indenyl, each aryl being substituted with 0-5 substituents independently selected at each occurrence from C1-6 alkyl, C3-6 cycloalkyl, methylenedioxy, C1-4 alkyloxy-C1-4 alkyloxy, —OR2m, Br, Cl, F, I, C1-4 haloalkyl, —CN, —NO2, —SH, —S(O)nR2n, —CO2R2m, —CO2R2m, —OC(O)R2n, —NR2gCOR2m, —N(COR2m)2, —NR2gCONR2oR2p, —NR2gCO2R2h, —NR2oR2p and CONR2oR2p;
• heteroaryl is selected from the group pyridyl, pyrimidyl, triazinyl, furanyl, quinolinyl, isoquinolinyl, thienyl, imidazolyl, thiazolyl, indolyl, pyrrolyl, oxazolyl, benzofuranyl, benzothienyl, benzothiazolyl, benzoxazolyl, isoxazolyl, triazolyl, tetrazolyl, indazolyl, 2,3-dihydrobenzo-furanyl, 2,3-dihydrobenzothienyl, 2,3-dihydro-benzothienyl-S-oxide, 2,3-dihydrobenzothienyl-s-dioxide, indolinyl, benzoxazolin-2-on-yl, benzodioxolanyl and benzodioxane, each heteroaryl being substituted at 0-4 carbon atoms with a substituent independently selected at each occurrence from the group C1-6 alkyl, C3-6 cycloalkyl, Br, F, I, C1-4 haloalkyl, —CN, NR2gR2h, nitro, —OR2m, —SH, —S(O)nR2n, COR2m, —CO2R2m, —OC(O)R2n, —NR2gCOR2m, —N(COR2m)2, NR2gCONR2oR2p and each heteroaryl being substituted at any nitrogen atom with 0-1 substituents selected from the group R2g, CO2R3a, COR3a and SO2R3a wherein,
• R3a is selected from the group C1-6 alkyl, C1-4 cycloalkyl-C1-6 alkyl and benzyl, each benzyl being substituted on the aryl moiety with 0-1 substituents selected from the group C1-4 alkyl, Br, Cl, F, I, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, and dimethylamino;
• R4 is independently selected at each occurrence from H, Br, Cl, F, I, —CN, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-8 cycloalkyl, C1-6 alkyloxy, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, amino, C1-4 alkylamino, (C1-4 alkyl)2 amino and phenyl, each phenyl is substituted with 0-3 groups selected from the group consisting of C1-7 alkyl, C3-8 cycloalkyl, Br, Cl, F, I, —(O)H, C1-4 haloalkyl, nitro, C1-4 alkoxy, C1-4 haloalkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-6 alkylamino and (C1-4 alkyl)2 amino and wherein R4 n-phenyl groups may be substituted with 0-5 substituents selected from OH, halogen, —C(O)H, —OC1-6-alkyl and C1-6 haloalkyl, C1-6 alkyl, C3-7 c-alkyl, C1-6 alkyl(OH)nCO2R wherein R is H or C1-6 alkyl, C1-6 alkyl (OH)n, wherein n is 0-3;
• R6, R6a and R7 are independently selected from:
• H, C1-10 alkyl, C3-10 cycloalkyl, C3-10 alkenyl, C3-10 alkynyl, C1-10 haloalkyl, C2-8 alkoxyalkyl, C4-12 cycloalkylalkyl, C5-10 cycloalkenyl, and C6-14 cycloalkenylalkyl;
• R6, R6a and R7 are substituted with 0-6 substituents independently selected from halogen, C1-4 alkyl, C3-8 cycloalkyl, C1-6 alkyloxy and C1-4 haloalkyl.