Patent ID: 6358976
Filing Date: 2002-03-19
Classification: A61P,C07D

Abstract:
A compound of Formula IV: including stereoisomeric forms thereof, or mixtures of stereoisomeric forms thereof, or pharmaceutically acceptable salt forms thereof wherein:R1 is selected from: R2 and R3 are independently selected from: H, C1-C4 alkoxy, NR11R12, halogen, NO2, CN, CF3, C1-C6 alkyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl), aryl(C1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, arylcarbonyl, and aryl substituted with 0-4 R7; alternatively, when R2 and R3 are substituents on adjacent atoms, they can be taken together with the carbon atoms to which they are attached to form a 5-7 membered carbocyclic or 5-7 membered heterocyclic aromatic or nonaromatic ring system, said carbocyclic or heterocyclic ring being substituted with 0-2 groups selected from C1-C4 alkyl, C1-C4 alkoxy, halo, cyano, amino, CF3 and NO2; R2a is selected from: H, C1-C10 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl), aryl, aryl(C1-C4 alkyl)-, (C2-C7 alkyl)carbonyl, arylcarbonyl, (C2-C10 alkoxy)carbonyl, C3-C7 cycloalkoxycarbonyl, C7-C11 bicycloalkoxycarbonyl, aryloxycarbonyl, aryl(C1-C10 alkoxy)carbonyl, C1-C6 alkylcarbonyloxy(C1-C4 alkoxy)carbonyl, arylcarbonyloxy(C1-C4 alkoxy)carbonyl, and C3-C7 cycloalkylcarbonyloxy(C1-C4 alkoxy)carbonyl; R4 is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, heteroaryl, aryl(C1-C6 alkyl)-, and heteroaryl(C1-C6 alkyl)-, wherein said aryl or heteroaryl groups are substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; R6 is selected from: H, C1-C10 alkyl, hydroxy, C1-C10 alkoxy, nitro, C1-C10 alkylcarbonyl, â€”N(R11)R12, cyano, halo, CF3, CHO, CO2R18b, C(&boxH;O)R18b, CONR17R18b, OC(&boxH;O)R10, OR10, OC(&boxH;O)NR10R11, NR10C(&boxH;O)R10, NR10C(&boxH;O)OR21, NR10C(&boxH;O)NR10R11, NR10SO2NR10R11, NR10SO2R21, S(O)pR11, SO2NR10R11, aryl substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)mMe, and â€”NMe2, aryl(C1-C4 alkyl)-, said aryl being substituted with 0-3 groups selected from halogen, C1-C6 alkoxy, C1-C6 alkyl, CF3, S(O)pMe, 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 R7; R7 is selected from: H, hydroxy, C1-C4 alkyl, C1-C4 alkoxy, aryl, aryl(C1-C4 alkyl)-, (C1-C4 alkyl)carbonyl, CO2R18a, SO2R11, SO2NR10R11, OR10, and N(R11)R12; U is selected from: â€”(CH2)nâ€”, â€”(CH2)nO(CH2)mâ€”, â€”NH(CH2)nâ€”, â€”N(R10)C(&boxH;O)â€”, â€”NHC(&boxH;O)(CH2)nâ€”, and â€”C(&boxH;O)N(R10)â€”; G is N; R8 is selected from: H, CO2R18b, C(&boxH;O)R18b, CONR17R18b, C1-C10 alkyl substituted with 0-1 R6, C2-C10 alkenyl substituted with 0-1 R6, C2-C10 alkynyl substituted with 0-1 R6, C3-C8 cycloalkyl substituted with 0-1 R6, C5-C6 cycloalkenyl substituted with 0-1 R6, (C1-C10 alkyl)carbonyl, C3-C10 cycloalkyl(C1-C4 alkyl)-, phenyl substituted with 0-3 R6, naphthyl substituted with 0-3 R6, 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 R7; R9 is selected from: C1-C10 alkyl substituted with 0-1 R6, C1-C10 alkoxy substituted with 0-2 R7, H, nitro, N(R11)R12, OC(&boxH;O)R10, OR10, OC(&boxH;O)NR10R11, NR10C(&boxH;O)R10, NR10C(&boxH;O)OR21, NR10C(&boxH;O)NR10R11, NR10SO2NR10R11, NR10SO2R21, hydroxy, OR22, â€”N(R10)R11, â€”N(R16)R17, aryl(C0-C6 alkyl)carbonyl, aryl(C1-C6 alkyl), heteroaryl(C1-C6 alkyl), CONR18aR20, SO2R18a, and SO2NR18aR20, providing that any of the above alkyl, aryl or heteroaryl groups may be unsubstituted or substituted independently with 1-2 R7; R10 is selected from: H, CF3, C3-C6 alkenyl, C3-C11 cycloalkyl, aryl, (C3-C11 cycloalkyl)methyl, aryl(C1-C4 alkyl), and C1-C10 alkyl substituted with 0-2 R6; R11 is selected from: H, hydroxy, C1-C8 alkyl, C3-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl)methyl, C1-C6 alkoxy, benzyloxy, aryl, heteroaryl, heteroaryl(C1-C4 alkyl)-, aryl(C1-C4 alkyl), adamantylmethyl, and C1-C10 alkyl substituted with 0-2 R4; R12 is selected from: H, C1-C6 alkyl, triphenylmethyl, methoxymethyl, methoxyphenyldiphenylmethyl, trimethylsilylethoxymethyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, (C1-C6 alkyl)aminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl, heteroaryl(C1-C6 alkyl)carbonyl, heteroarylcarbonyl, aryl(C1-C6 alkyl)-, (C1-C6 alkyl)carbonyl, arylcarbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, aryl(C1-C6 alkyl)sulfonyl, heteroarylsulfonyl, heteroaryl(C1-C6 alkyl)sulfonyl, aryloxycarbonyl, and aryl(C1-C6 alkoxy)carbonyl, wherein said aryl groups are substituted with 0-2 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, halo, CF3, and nitro; R16 is selected from: â€”C(&boxH;O)OR8a, â€”C(&boxH;O)R18b, â€”C(&boxH;O)N(R18b)2, â€”SO2R18a, and â€”SO2N(R18b)2; R17 is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl, C3-C7 cycloalkyl(C1-C4 akyl)-, aryl, aryl(C1-C6 alkyl)-, and heteroaryl(C1-C6 alkyl); R18a is selected from: C1-C8 alkyl, C3-C11 cycloalkyl, aryl(C1-C6 alkyl)-, said aryl substituted with 0-4 R19, heteroaryl(C1-C6 alkyl)-, said heteroaryl substituted with 0-4 R19, (C1-C6 alkyl)heteroaryl, said heteroaryl substituted with 0-4 R19, heteroaryl substituted with 0-4 R19, phenyl substituted with 0-4 R19, and naphthyl substituted with 0-4 R19; R18b is H or R18a; R19 is selected from: H, halogen, CF3, CO2H, CN, NO2, â€”NR11R12, OCF3, C1-C8 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C11 cycloalkyl, C3-C7 cycloalkyl(C1-C4 alkyl)-, aryl(C1-C6 alkyl)-, C1-C6 alkoxy, C1-C4 alkoxycarbonyl, aryl, aryl-Oâ€”, aryl-SO2â€”, heteroaryl, and heteroaryl-SO2â€”, wherein said aryl and heteroaryl groups are substituted with 0-4 groups selected from hydrogen, halogen, CF3, C1-C3 alkyl, and C1-C3 alkoxy; R20 is selected from: hydroxy, C1-C10 alkyloxy, C3-C11 cycloalkyloxy, aryloxy, aryl(C1-C4 alkyl)oxy, C2-C10 alkylcarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyloxy(C1-C2 alkyl)oxy-, C2-C10 alkoxycarbonyl(C1-C2 alkyl)oxy-, C3-C10 cycloalkylcarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyloxy(C1-C2 alkyl)oxy-, C3-C10 cycloalkoxycarbonyl(C1-C2 alkyl)oxy-, aryloxycarbonyl(C1-C2 alkyl)oxy-, aryloxycarbonyloxy(C1-C2 alkyl)oxy-, arylcarbonyloxy(C1-C2 alkyl)oxy-, C1-C5 alkoxy(C1-C5 alkyl)carbonyloxy(C1-C2 alkyl)oxy-, (5-(C1-C5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, and (R10)(R11)Nâ€”(C1-C10 alkoxy)-; R21 is selected from: C1-C8 alkyl, C2-C6 alkenyl, C3-C11 cycloalkyl, (C3-C11 cycloalkyl)methyl, aryl, aryl(C1-C4 alkyl)-, and C1-C10 alkyl substituted with 0-2 R7; R22 is selected from: â€”C(&boxH;O)â€”R18b, â€”C(&boxH;O)N(R18b)2, â€”C(&boxH;O)NHSO2R18a, â€”C(&boxH;O)NHC(&boxH;O)R18b, â€”C(&boxH;O)NHC(&boxH;O)OR18a, and â€”C(&boxH;O) NHSO2NHR18b; m is 0-2; n is 0-4; and p is 0-2; with the following proviso: (1) n and m are chosen such that the number of atoms connecting R1 and â€”COR20 in Formula (IV) is in the range of 10-14.