Patent ID: 6489333
Filing Date: 2002-12-03
Classification: A61P,C07D

Abstract:
A compound of Formula (IG): or stereoisomeric forms thereof, tautomeric forms thereof, pharmaceutically acceptable salt forms thereof or prodrug forms thereof, wherein:G is selected from: D1 is selected from: NR2R4, OR3, SR3, F, Cl, Br, CF3, and C1-C4 alkyl; R2 at each occurrence is independently selected from: H, OR3, C1-C6 alkyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, (C0-C6 alkyl)aminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl(C0-C4 alkyl), C3-C7 cycloalkyl(C0-C4 alkyl)carbonyl, C3-C7 cycloalkyl(C0-C4 alkoxy)carbonyl, aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), aryl(C0-C6alkyl)carbonyl, heteroaryl(C0-C6 alkyl)carbonyl, C1-C6 alkylsulfonyl, aryl(C0-C6 alkyl)sulfonyl, heteroaryl(C0-C6 alkyl)sulfonyl, aryl(C1-C6 alkoxy)carbonyl, and heteroaryl(C1-C6 alkoxy)carbonyl, 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; R3 at each occurrence is independently selected from: H, C1-C6 alkyl, (C1-C6 alkyl)carbonyl, (C1-C6 alkoxy)carbonyl, (C0-C6 alkyl)aminocarbonyl, C3-C6 alkenyl, C3-C7 cycloalkyl(C0-C4 alkyl), C3-C7 cycloalkyl (C0-C4 alkyl) carbonyl, cycloalkyl (C0-C4 alkoxy)carbonyl, aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), aryl (C0-C6 alkyl) carbonyl, heteroaryl (C0-C6 alkyl)carbonyl, aryl(C1-C6 alkoxy)carbonyl, and heteroaryl(C1-C6 alkoxy)carbonyl, 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; R4 is selected from: H, C1-C6 alkyl, C1-C6 alkylcarbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C4 alkyl), C3-C7 cycloalkyl(C0-C4 alkyl)carbonyl, cycloalkyl(C0-C4 alkoxy)carbonyl, aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), aryl(C0-C6 alkyl)carbonyl, heteroaryl(C0-C6 alkyl)carbonyl, aryl(C1-C6 alkoxy)carbonyl, and heteroaryl(C1-C6 alkoxy)carbonyl, 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; alternatively, R2 and R4 when both substituents on the same nitrogen atom as in (â€”NR2R4) can be taken together with the nitrogen atom to which they are attached to form a heterocycle selected from 1-aziridinyl, 1-azetidinyl, 1-piperidinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl; said heterocycle being optionally substituted with 0-3 groups selected from oxo, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C4 alkyl), C1-C6 alkylcarbonyl, C3-C7 cycloalkyl(C0-C5 alkyl)carbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C5 alkoxy)carbonyl, aryl(C0-C5 alkyl), heteroaryl(C0-C5 alkyl), aryl(C1-C5 alkoxy)carbonyl, heteroaryl(C1-C5 alkoxy)carbonyl, C1-C6 alkylsulfonyl, arylsulfonyl, and heteroarylsulfonyl; R5 is selected from: H, NR2R4, OR3, NO2, NO, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C4 alkyl), aryl(C0-C6 alkyl), or heteroaryl(C0-C6 alkyl), wherein said aryl and 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, NR2R4, OR3, C1-C6 alkyl, aryl(C0-C5 alkyl), heteroaryl(C0-C5 alkyl), CF3, F, Cl, and Br, 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; alternatively, R5 and R6, when substituents on adjacent carbon atoms, are taken together with the carbon atoms to which they are attached to form a 5-7 membered heterocyclic ring containing 1, 2 or 3 nitrogen atoms or a 5-7 membered carbocyclic ring, said carbocyclic or heterocyclic ring being aromatic or nonaromatic, said carbocyclic or heterocyclic ring being substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, NO2 and aryl, wherein said aryl 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; R7 is selected from: H, C1-C4 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, aryl(C0-C4 alkyl), and heteroaryl(C0-C4 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; alternatively, â€”NHR2 and R7, when substituents on adjacent atoms, are taken together with the atoms to which they are attached to form a 5-7 membered heterocyclic ring containing 2 or 3 nitrogen atoms, said heterocyclic ring being aromatic or nonaromatic, said heterocyclic ring being substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, NO2, and aryl, wherein said aryl 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; U1 is selected from: â€”(CH2)n-, â€”Q1-(CH2)m-, â€”(CH2)m-Q2â€”, â€”(CH2)t-Q2-CH2â€”, â€”CH2-Q2-(CH2)t-, â€”(CH2)t-N(R3)â€”C(&boxH;O)â€”, â€”(CH2)t-N(R3)â€”S(&boxH;O)2â€”, â€”(CH2)t-C(&boxH;O)â€”N(R3)â€”, â€”(CH2)t-S(&boxH;O)2â€”N(R3)â€”, â€”C(&boxH;O)â€”N(R4)â€”(CH2)t-, â€”N(R4)â€”, â€”N(R4)â€”(CH2)q-Q2-, â€”N(R4)â€”C(&boxH;O)â€”(CH2)r-, and â€”N(R4)â€”(CH2)t-C(&boxH;O)â€”; U2 is selected from: â€”(CH2)h-, â€”Q1-(CH2)r-, â€”(CH2)r-Q2-, â€”(CH2)i-N(R3)â€”C(&boxH;O)â€”, â€”(CH2)i-N(R3)â€”S(&boxH;O)2â€”, â€”(CH2)i-C(&boxH;O)â€”N(R3)â€”, â€”(CH2)i-S(&boxH;O)2â€”N(R3)â€”, â€”(CH2)i-Q2â€”CH2â€”, â€”CH2-Q2-(CH2)i-, â€”C(&boxH;O)â€”N(R4)â€”(CH2)i-, â€”N(R4)â€”, â€”N(R4)â€”(CH2)2-Q2-, â€”N(R4)â€”C(&boxH;O)â€”(CH2)i-, and â€”N(R4)â€”(CH2)t-C(&boxH;O)â€”; U4 is selected from: â€”(CH2)h-, â€”(CH2)2-Q2, â€”(CH2) 2â€”Oâ€”CH2â€”, â€”(CH2)r-C(&boxH;O)â€”, â€”C(&boxH;O)â€”(CH2)r-, and â€”C(&boxH;O)â€”N(R4)â€”(CH2)r; Q1 is â€”Oâ€”, â€”Sâ€”, or N(R4); Q2 is â€”Oâ€”, â€”Sâ€”, â€”S(&boxH;O)â€”, â€”S(&boxH;O)2â€”, or N(R3); R8 and R9 are independently selected from: H, C1-C10 alkyl, NO2, CF3, F, Cl, Br, C1-C10 alkylcarbonyl, â€”NR2R4, OC(&boxH;O)OR10, OR10, OC(&boxH;O)NR10R11, OCH2CO2R10, CO2CH2CO2R10, CO2R10, C(&boxH;O)R10, NR10C(&boxH;O)R11. NR7C(&boxH;O)OR10, NR7C(&boxH;O)NR10R11, NR7SO2NR10R11, NR7SO2R10, SR10, SR10, S(&boxH;O)R10, SO2R10, SO2NR10R11, SiMe3, R10OOC(C1-C6 alkyl). R2R4N(C2-C6 alkyl), R10OOC(C1-C6 alkoxy), R2R4N(C2-C6 alkoxy), C2-C6 alkenyl, C3-C10 cycloalkyl, C3-C10 cycloalkylmethyl, aryl, and aryl(C1-C5 alkyl)-, wherein said aryl groups are substituted with 0-2 substituents independentyl selected from a group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; R10 and R11 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 substitutents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2, alternatively, R10 and R11 when both substituents on the same nitrogen atom an in (â€”NR10R11) can be taken together with the nitrogen atom to which are attached to form a heterocycle selected from 1-aziridinyl, 1-azetidinyl, 1-piperridinyl, 1-morpholinyl, 1-pyrrolidinyl, thiamorpholinyl, thiazolidinyl, and 1-piperazinyl; said heterocycle being optionally substituted with 0-3 groups selected from oxo, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C4 alkyl), C1-C6 alkylcarbonyl, C3-C7 cycloalkyl(C0-C5 alkyl) carbonyl, C1-C6 alkoxycarbonyl, C3-C7 cycloalkyl(C0-C5 alkoxy)carbonyl, aryl(C0-C5 alkyl), heteroaryl(C0-C5 alkyl), aryl(C1-C5 alkoxy)carbonyl, heteroaryl(C1-C5 alkoxy) carbonyl, C1-C6 alkylsulfonyl arysulfonyl and heteroarysulfonyl; W is selected form : â€”(C(R12)2)pC(&boxH;O)N(R13)-, and â€”C(&boxH;O)â€”N(R13)-(C(R12)2)p-; X is â€”(C(R12)2)pC(R12)(R14)-C(R12)2- or â€”(C(R12)2)p-C(R12)(R15)-; alternatively, W and X can be taken together to be R12 at each occurence is independently selected from: H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C7 cycloalkyl(C0-C4 alkyl)-, (C1-C4 alkyl)carbonyl, aryl(C0-C6 alkyl), and heteroaryl(C0-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; R13 is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C6 alkyl), aryl(C0-C6 alkyl), or heteroaryl(C0-C6 alkyl), wherein said aryl and heteroaryl groups substituted with 0-2 substituents independently selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; R14 is selected from: H, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C1-C6 hydroxyalkyl, C1-C6 alkoxy(C1-C6 alkyl), aryl(C0-C6 alkoxy C1-C6 alkyl), C1-C6 alkylthio(C1-C6 alkyl), C1-C6 alkylsulfonyl(C1-C6 alkyl), aryl(C0-C6 alkylthio C1-C6 alkyl), aryl(C0-C6 alkylsulfonyl C1-C6 alkyl), C3-C10 cycloalkyl(C0-C6 alkyl), aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), R17R20NC(&boxH;O)(C1-C4 alkyl), R10OC(&boxH;O)(C1-C4 alkyl), and R17R20N(C1-C4 alkyl), provided that any of the above alkyl, cycloalkyl, aryl or heteroaryl groups may optionally by substituted independently with 0-1 R16 or 0-2 R8; R15 is selected from: H, R16, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl (C0-C6 alkyl), C1-C6 alkoxy(C1-C6 alkyl), C1-C6 alkylamino(C1-C6 alkyl), C2-C10 dialkylamino (C1-C6 alkyl), (C1-C10 alkyl)carbonyl, aryl(C0-C6 alkyl)carbonyl, heteroaryl(C0-C6 alkyl)carbonyl, aryl(C0-C6 alkyl), heteroaryl(C0-C6 alkyl), CO2R17, C(&boxH;O)R17, CONR17R20, SO2NR17R20, 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; Y is selected from â€”C(&boxH;O)R19, â€”SO3H, and â€”PO3H; R16 is selected from: â€”N(R20)-C(&boxH;O)-O-R17, â€”N(R20)-C(&boxH;O)-R17, â€”N(R20)-C(&boxH;O)-NH-R17, â€”N(R20)SO2-R17, and â€”N(R20)SO2-NR20R17; R17 is selected from: C1-C10 alkyl, C3-C10 cycloalkyl, aryl(C0-C6 ), heteroaryl(C0-C6 alkyl), arylaryl(C0-C6 alkyl), heteroarylaryl(C0-C6 alkyl), arylheteroaryl(C0-C6 alkyl), and heteroarylheteroaryl (C0-C6 ), wherein said aryl or heteroaryl groups are optionally subtituted with 0-3 substituents independently selected from the group consisting of: C1-C4 alkyl, C1-C4 alkoxy, aryl, F, Cl, Br, CN, NH2, CF3, and NO2; R18 is selected from: H, â€”C(&boxH;O)OR17, â€”C(&boxH;O)R17, â€”C(&boxH;O)NHR17, â€”SO2R17. â€”SO2NR20R17, C1-C10 alkyl, C3-C10 cycloalkyl (C0-C6 alkyl), aryl (C0-C6 alkyl), and heteroaryl(C0-C6 alkyl), wherein said aryl group is optionally substituted with 0-3 substituents independently selected from the group consisting of: C1-C4 alkyl, C1-C4 alkoxy, aryl, F, Cl, Br, â€”CN, â€”NH2, â€”CF3, and â€”NO2; R19 is selected from: hydroxy, C1-C10 alkoxy, C3-C10 cycloalkyloxy, aryloxy, aryl(C1-C6 alkoxy), C2-C10 alkylcarbonyloxy(C1-C2 alkyl)oxy, C2-C10 alkoxycarbonylloxy(C1-C2 alkyl)oxy, C2-C10 alkoxycarbonyl(C1-C2 alkyl)oxy, C3-C10 cycloalkylcarbonyloxy(C1-C2 )oxy, C3-C10 cycloalkoxycarbonylox(C1-C2 alkyl)oxy, C3-C10 cycloalkoxycarbonyl(C1-C2 alkyl)oxy, aryloxycarbonyl(C1-C2 alkyl)oxy, aryloxycarbonyloxy(C1-C2 alkyl)oxy, arylcarbonylloxy(C1-C2 alkyl)oxy, C1-C5 alkoxy(C1-C5 alkyl)carbonyloxy(C1-C1-C2 alkyl)oxy, (5-(C1-C5 alkyl)-1,3-dioxa-cyclopenten-2-one-yl)methoxyloxy, (5-aryl-1,3-dioxa-cyclopenten-2-one-yl)methyloxy, (R10)(R11)N-(C1-C10 alkoxy) and â€”(CH2)kN+(R21)(R22)(R23)z-; R20 is selected from: H, C1-C6 alkyl, C3-C7 cycloalkyl(C0-C6 alkyl)-, aryl, aryl(C0-C6 alkyl)-, and heteroaryl(C0-C6 alkyl), wherein said aryl or hetroaryl groups are optionally substituted with 0-3 substituents independently selected from the group consisting of: C1-C4 alkyl, C1-C4 alkoxy, F, Cl, Br, CF3, and NO2; z- is a pharmaceutically acceptable anion selected from halide, bisulfate, sulfae, hydrogenphosphate, phosphate, toluenesulfonate, methanesulfonate, ethanesulfonate, acetate, trifluoroacetate, citrate, oxalate, succinate, and molonate; R22, R22 and R23 are independently selected from: H, C1-C9 alkyl, C-C7 cycloalkyl(C0-C4 alkyl), aryl (C0-C6 alkyl), heteroaryl, and heteroaryl(C0-C6 alkyl), wherein said alkyl or aryl groups are substituted with 0-2 substituents selected from the group consisting of C1-C4 alkyl, C1-C4 alkoxy, OH, F, Cl, Br, CF3, and NO2; alternatively R21 and R22 can be taken together to form a 5-7 membered heterocyclic aromatic or non-aromatic ring system containing 1-3 heteroatoms selected from N, O and S and R23 is defined as above or R21, R22, and R23can be taken together to form a heterobicyclic ring system containing 1-3 heteroatoms selected from N, O and S, wherein said heterocyclic or heterobicyclic ring being substituted with 0-2 groups selected from C1-C4 alkyl, C1-C4 alkoxy, halo, â€”CN, â€”NH2, â€”CF3, and â€”NO2; h is 0-4; i is 0-2; k is 2-6; m is 1-4; n is 0-5; q is 2-3; r is 0-3; t is 1-3; and p is 0-2; provided that h, i, m, n, q, r, t, and p at each occurrence, are chosen such that the number of in-chain atoms between Y and the pyrimidine, pyrimidone, triazine or triazinone of G is in the range of 8-12.