Patent ID: 6476226
Filing Date: 2002-11-05
Classification: A61P,C07D

Abstract:
A compound of Formula (I): or a pharmaceutically acceptable salt form thereof wherein:b is a single or double bond; R1 is selected from: R2a(R3)Nâ€”Vâ€”, R2(R2b)N(R3N&boxH;)Câ€”Vâ€”, R2(R2b)N(R3N&boxH;)CNHâ€”Vâ€”, R2(R11O)N(R3N&boxH;)Câ€”Vâ€”, R2(R2b)N(R11ON&boxH;)Câ€”Vâ€”, V is selected from: -(C1-C4 alkyl)-, -(C2-C4 alkenyl)-, -(C2-C4 alkynyl)-, -(phenyl)-, said phenyl substituted with 0-2 groups independently selected from R9, -(pyridyl)-, said pyridyl substituted with 0-2 groups independently selected from R9, and -(pyridazinyl)-, said pyridazinyl substituted with 0-2 groups independently selected from R9; Z is selected from: a bond, O, S, S(&boxH;O), and S(&boxH;O)2; R2a is R2 or R2(R2b)N(R3N&boxH;)Câ€”; R2, R2b, and R3 are independently selected from: H, C1-C10 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl(C1-C4 alkyl)-, C2-C7 alkylcarbonyl, C1-C4 haloalkyl, aryl, arylcarbonyl, aryl(C1-C4 alkyl)-, diarylmethyl, 2,2-diarylethyl, benzhydryl(C1-C4 alkyl)-, heteroaryl, heteroaryl(C1-C4 alkyl)-, and a group selected from: C1-C6 alkoxycarbonyl, C3-C11 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C1-C10 alkoxy)carbonyl, (C1-C6 alkyl)carbonyloxy(C1-C4alkoxy)carbonyl, arylcarbonyloxy(C1-C4alkoxy)carbonyl, and (C3-C11 cycloalkyl)carbonyloxy(C1-C4 alkoxy)carbonyl, wherein at least one of R2, R2b, and R3 is H or the group selected from: C1-C6 alkoxycarbonyl, C3-C11 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C1-C10 alkoxy)carbonyl, (C1-C6 alkyl)carbonyloxy(C1-C4 alkoxy)carbonyl, arylcarbonyloxy(C1-C4 alkoxy)carbonyl, and (C3-C11 cycloalkyl)carbonyloxy(C1-C4 alkoxy)carbonyl; wherein said aryl groups of R2, R2b, and R3 may be substituted with 0-3 groups selected from hydroxy, halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, â€”CN, â€”SO2(C1-C4 alkyl), â€”S(C1-C4 alkyl), â€”SO2NH2, â€”NR21R22, C1-C4 haloalkyl, methylenedioxydiyl, and ethylenedioxydiyl; and said heteroaryl groups of R2, R2b, and R3 may be substituted with 0-2 groups selected from hydroxy, halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, SO2CH3, and â€”NR21R22; alternatively, R2 and R2b, can be taken together with the nitrogen atom to which they are attached to form a 5-14 membered heterocyclic ring optionally containing one additional heteroatom selected from: N, O, or S; said heterocyclic ring being monocyclic, bicyclic, or tricyclic; said heterocyclic ring being substituted with 0-3 R4; R4, when a substituent on carbon, is independently selected from H, C1-C4 alkyl, aryl, aryl(C1-C6 alkyl)-, C1-C4 alkoxy, halogen, methylenedioxydiyl, (C1-C6 alkyl)SO2NHâ€”, (C6-C1-l aryl)SO2NHâ€”, (C1-C6 alkyl)CONHâ€”, (C6-C11 aryl)CONHâ€”, (C1-C6 alkyl)NHCOâ€”, (C6-C11 aryl)NHCOâ€”, (C1-C6 alkyl)NHCOâ€”, (C6-C11 aryl)NHCOâ€”, (C1-C6 alkyl)NHSO2â€”, (C6-C11 aryl)NHSO2â€”, (C1-C6 alkyl)SO2â€”, (C6-C11 aryl)SO2â€”, wherein said aryl groups may be optionally substituted with 0-3 groups selected from hydroxy, halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, OCF3, SCH3, S(O)CH3, SO2CH3, â€”NR21R22, C1-C4 haloalkyl, methylenedioxydiyl, and ethylenedioxydiyl; alternatively, when two R4 groups are attached to adjacent carbon atoms, they may be taken together with the atoms to which they are attached to form a fused 5-7 membered saturated, unsaturated or aromatic carbocyclic ring; alternatively, when R4 is attached to a saturated carbon atom, it may also be &boxH;O or &boxH;S; R4, when a substituent on nitrogen, is independently selected from: H, C1-C6 alkyl, C3-C6 alkenyl, C1-C10 alkoxycarbonyl, C1-C10 alkylcarbonyl, C1-C10 alkylsulfonyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl(C1-C4 alkyl)-, C3-C11 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, aryl, aryl(C1-C10 alkyl)-, diarylmethyl, 2,2-diarylethyl, benzhydryl(C1-C4 alkyl)-, arylcarbonyl, aryloxycarbonyl, arylsulfonyl, aryl(C1-C10 alkyl)sulfonyl, aryl(C2-C10 alkenyl)sulfonyl, aryl(C1-C10 alkoxy)carbonyl, heteroaryl, heteroarylsulfonyl, heteroarylcarbonyl, heteroaryl(C1-C10 alkyl)-, and heteroaryl(C1-C10 alkyl)carbonyl, wherein said aryl or heteroaryl groups may be additionally substituted with 0-2 groups selected from hydroxy, halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, SCH3, SOCH3, SO2CH3, and â€”NR21R22; R4, when a substituent on sulfur, may be &boxH;O; G is C(R7); X is â€”CH2â€”CH(Wa)â€”, â€”CH(Wb)â€”CH2â€” or â€”CH(Wb)â€”; Y is selected from hydroxy, C1-C10 alkyloxy, C3-C11 cycloalkyloxy, C6-C10 aryloxy, C7-C11 arylalkyloxy, C2-C10 alkylcarbonyloxyalkyloxy, C2-C10 alkoxycarbonyloxyalkyloxy, C2-C10 alkoxycarbonylalkyloxy, C4-C10 cycloalkylcarbonyloxyalkyloxy, C4-C10 cycloalkoxycarbonyloxyalkyloxy, C4-C10 cycloalkoxycarbonylalkyloxy, C7-C11 aryloxycarbonylalkyloxy, C7-C12 aryloxycarbonyloxyalkyloxy, C7-C12 arylcarbonyloxyalkyloxy, C4-C10 alkoxyalkylcarbonyloxyalkyloxy, (5-(C1-C4 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, and (R28)(R29)N-(C1-C10 alkoxy)-; Wa is selected from: H, hydroxy, â€”NR16R20, â€”NR25R26, C1-C10 alkoxy, C1-C10 alkyl substituted with 0-3 R8, and aryl substituted with 0-3 R8; Wb is selected from: H, CH2OH, CH2OR12, CH2C2R12, CH2C(&boxH;O)NHR18, CH2NR16R20, CH2NR25R26, C3-C6 alkenyl, C3-C10 cycloalkyl, C4-C11 cycloalkylmethyl, C1-C8 alkyl substituted with 0-2 R8, aryl substituted with 0-3 R8, and aryl(C1-C6 alkyl), said aryl substituted with 0-3 R8; R5 is selected from: H, hydroxy, fluoro, â€”NH(CH2)sR8, â€”NH(CH2)sCO2R12, â€”O(CH2)sCO2R2, â€”NR25R26, C1-C8 alkyl substituted with 0-2 R8, C1-C10 alkoxy substituted with 0-2 R8, C3-C6 alkenyl, C4-C11 cycloalkylmethyl, and aryl(C1-C6 alkyl)-; R6 is H, methyl, or fluoro; alternatively, R5 and R6 can be taken together to be &boxH;0, &boxH;CHR8a or &boxH;CHCH2R8; R7 is selected from: H, hydroxy, â€”OR12, â€”OC(&boxH;O)R13, â€”OC(&boxH;O)OR14, â€”OC(&boxH;O)NR23R24, and â€”O(CH2)sCO2R12; alternatively, when G is C(R7), R7 and R6 may be taken together to form a carbon-carbon double bond; R7a and R7b are independently selected from H, methyl, ethyl, and &boxH;O; alternatively, when R7 and R7a occur on adjacent carbons R7 and R7a may be taken together to form a carbon-carbon double bond; alternatively, when R7a and R7b occur on adjacent carbons R7a and R7b may be taken together to form a six carbon aromatic ring; R8 is selected from: H, hydroxy, cyano, â€”C2R12, â€”C(&boxH;O)R13, â€”OC(&boxH;O)R13, â€”OC(&boxH;O)OR14, â€”OR12, â€”OCH2CO2R12, â€”CO2CH2CO2R12, â€”OC(&boxH;O)NR23R24, â€”C(&boxH;O)NR23R24, â€”NR25R26, â€”NR27C(&boxH;O)R13, â€”NR27C(&boxH;O)OR14, â€”NR27SO2R14, â€”SR14, â€”SOR14, â€”SO2R14, â€”SO2NR23R24, C1-C10 alkoxy, C1-C10 alkylcarbonyl, C2-C6 alkenyl, C3-C10 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, wherein said aryl is substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, CO2R12, SO2Me, SOMe, SMe and â€”NMe2, aryl(C1-C4 alkyl)-, wherein said aryl is substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, CO2R12, SO2Me, SOMe, SMe, and â€”NMe2, and a 5-10 membered heterocyclic ring containing 1-3 N, O, or S heteroatoms, wherein said heterocyclic ring may be saturated, partially saturated, or fully unsaturated, said heterocyclic ring being substituted with 0-2 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, CO2R12, SO2Me, SOMe, SMe and â€”NMe2; R8a is selected from: H, cyano, â€”C2R12, â€”C(&boxH;O)R13, â€”C(&boxH;O)NR23R24, C1-C10 alkylcarbonyl, C2-C6 alkenyl, C3-C10 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, wherein said aryl is substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, CO2R12, SO2Me, SOMe, SMe and â€”NMe2, and aryl(C1-C4 alkyl)-, wherein said aryl is substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, CO2R12, SO2Me, SOMe, SMe, and â€”NMe2; R9 is selected from H, halogen, CF3, CN, C1-C4 alkyl, and C1-C4 alkoxy; R10 is selected from: H, hydroxy, CN, carboxy, â€”NR25R26; C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl, C7-C14 bicycloalkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C6 alkylsulfinyl, C1-C6 alkylsulfonyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, aryl, piperidinyl, morpholinyl, and pyridinyl; R11 is selected from: H, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, aryl(C1-C4 alkyl)-, and C1-C10 alkyl substituted with 1-2 R10; R12 is selected from: H, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, aryl(C1-C4 alkyl)-, and C1-C10 alkyl substituted with 1-2 R10; R13 is selected from: hydrogen, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, aryl(C1-C4 alkyl)-, heteroaryl, heteroaryl(C1-C4 alkyl)-, and C1-C10 alkyl substituted with 1-2 R10; R14 is selected from: C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, aryl(C1-C4 alkyl)-, and C1-C10 alkyl substituted with 1-2 R10; R15 is selected from: H, OH, â€”OR12, â€”CO2R12, â€”C(&boxH;O)NR23R24, â€”OC(&boxH;O)NR23R24, C1-C10 alkoxycarbonyl substituted with 0-2 R8; C1-C10 alkyl substituted with 0-3 R8; C2-C10 alkenyl substituted with 0-3 R8; and C1-C10 alkoxy substituted with 0-3 R8; R16 is selected from: â€”C(&boxH;O)OR17, â€”C(&boxH;O)R18, â€”C(&boxH;O)NR17R18, â€”C(&boxH;O)NHSO2R17, â€”C(&boxH;O)NHC(&boxH;O)R17, â€”C(&boxH;O)NHC(&boxH;O)OR17, â€”C(&boxH;O)NHSO2NHR17, â€”SO2R17, â€”SO2NR17R18, and â€”SO2NHC(&boxH;O)OR17; R17 is selected from: C1-C8 alkyl substituted with 0-2 R19, C3-C8 alkenyl substituted with 0-2 R19, C3-C8 alkynyl substituted with 0-2 R19, C3-C8 cycloalkyl substituted with 0-2 R19, aryl substituted with 0-4 R19, aryl(C1-C6 alkyl)-substituted with 0-4 R19, a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R19, and C1-C6 alkyl substituted with a 5-10 membered heterocyclic ring system having 1-3 heteroatoms selected independently from O, S, and N, said heterocyclic ring being substituted with 0-4 R19; R18 is selected from H and R17; R19 is selected from: H, halogen, CF3, CN, NO2, NR25R26, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C11 cycloalkyl, C3-C11 cycloalkyl(C1-C4 alkyl)-, aryl, aryl(C1-C6 alkyl)-, C1-C6 alkoxy, and C1-C4 alkoxycarbonyl; R20 is selected from: H, C1-C10 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C3-C11 cycloalkyl(C1-C4 alkyl)-, aryl, and aryl(C1-C10 alkyl)-; R21 and R22 are each independently H, methyl, ethyl, propyl, or butyl; R23 is selected from: H, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, hydroxy, C1-C6 alkoxy, benzyloxy, aryl, aryl(C1-C4 alkyl)-, heteroaryl, heteroaryl(C1-C4 alkyl)-, adamantylmethyl, and C1-C10 alkyl substituted with 1-2 R10; R24 is selected from: C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C4-C11 cycloalkylmethyl, aryl, aryl(C1 -C4 alkyl)-, and C1-C10 alkyl substituted with 1-2 R10; R25 and R26 are, independently, selected from: H, C1-C10 alkyl, C1-C10 alkoxycarbonyl, C1-C10 alkylcarbonyl, C1-C10 alkylsulfonyl, aryl, aryl(C1-C4 alkyl)-, arylcarbonyl, aryloxycarbonyl, arylsulfonyl, aryl(C1-C10 alkoxy)carbonyl, aryl(C1-C10 alkyl)sulfonyl, aryl(C2-C10 alkenyl)sulfonyl, C2-C6 alkenyl, C3-C10 cycloalkyl, C3-C10 cycloalkyl(C1-C4 alkyl)-, C3-C10 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, heteroaryl, heteroarylcarbonyl, heteroarylsulfonyl, and heteroaryl(C1-C4 alkyl)carbonyl, wherein said aryl groups are optionally substituted with 1-3 substituents selected from the group consisting of: C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, and NO2; R27 is selected from H, methyl, ethyl, propyl, butyl, benzyl, phenethyl, cyclopropyl, and cyclopropylmethyl; R28 and R29 are independently selected from: H, C1-C8 alkyl, C3-C6 alkenyl, C3-C10 cycloalkyl(C0-C4 alkyl), aryl(C0-C4 alkyl), and heteroaryl(C0-C4 alkyl), wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; n is 0, 1, or 2; q is 1, 2, 3, or 4; r is 0, 1, or 2; and s is 1, 2, 3, or 4.