Patent ID: 6518306
Filing Date: 2003-02-11
Classification: A61P,C07C,C07D

Abstract:
A compound of Formula(I) wherein:R1 is â€”(CR4R5)nC(O)O(CR4R5)mR6, â€”(CR4R5)nC(O)NR4(CR4R5)mR6, â€”(CR4R5)nO(CR4R5)mR6, or â€”(CR4R5)rR6 wherein the alkyl moieties unsubstituted or substituted with one or more halogens; m is 0 to 2; n is 1 to 4; r is 0 to 6; R4 and R5 are independently selected hydrogen or C1-2 alkyl; R6 is hydrogen, methyl, hydroxyl, aryl, halo substituted aryl, aryloxyC1-3 alkyl, halo substituted aryloxyC1-3 alkyl, indanyl, indenyl, C7-11 polycycloalkyl, tetrahydrofuranyl, furanyl, tetrahydropyranyl, pyranyl, tetrahydrothienyl, thienyl, tetrahydrothiopyranyl, thiopyranyl, C3-6 cycloalkyl, or a C4-6 cycloalkyl containing one or two unsaturated bonds, wherein the cycloalkyl or heterocyclic moiety is unsubstituted or substituted by 1 to 3 methyl groups, one ethyl group, or an hydroxyl group; provided that: a) when R6 is hydroxyl, then m is 2; or b) when R6 is hydroxyl, then r is 2 to 6; or c) when R6 is 2-tetrahydropyranyl, 2-tetrahydrothiopyranyl, 2-tetrahydrofuranyl, or 2-tetrahydrothienyl, then m is 1 or 2; or d) when R6 is 2-tetrahydropyranyl, 2-tetrahydrothiopyranyl, 2-tetrahydrofuranyl,or 2-tetrahydrothienyl, then r is 1 to 6; e) when n is 1 and m is 0, then R6 is other than H in â€”(CR4R5)nO(CR4R5)mR6; X is YR2, fluorine, NR4R5, or formyl amine; Y is O or S(O)mâ€², mâ€² is 0, 1, or 2; X2 is O or NR8; X4 is H, R9, OR8, CN, C(O)R8, C(O)OR8, C(O)NR8R8, or NR8R8; R2 is independently selected from â€”CH3 or â€”CH2CH3 optionally substituted by 1 or more halogens; s is 0 to 4; Ar is phenyl unsubstituted or substitued by R7; Z is OR14, OR15, SR14, S(O)mâ€²R7, S(O)2NR10R14, NR10R14, NR14C(O)R9, NR10C(Yâ€²)R14, NR10C(O)OR7, NR10C(Yâ€²)NR10R14, NR10S(O)2NR10R14, NR10C(NCN)NR10R14, NR10S(O)2R7, NR10C(CR4NO2)NR10R14, NR10C(NCN)SR9, NR10C(CR4NO2(SR9, NR10C(NR10)NR10R14, NR10C(O)C(O)NR10R14, or NR10C(O)C(O)OR14; Yâ€² is O or S; R7 is â€”(CR4R5)qR12 or C1-6 alkyl wherein: the R12 or C1-6 alkyl group is unsubstituted or substituted one or more times by methyl or ethyl unsubstituted or substituted by 1-3 fluorines; â€”F; â€”Br; â€”Cl; â€”NO2; â€”NR10R11; â€”C(O)R8; â€”CO2R8; â€”O(CH2)2-4OR8; â€”O(CH2)qR8; â€”CN; â€”C(O)NR10R11; â€”O(CH2)qC(O)NR10R11; â€”O(CH2)qC(O)9; â€”NR10C(O)NR10R11; â€”NR10C(O)R11; â€”NR10C(O)OR9; â€”NR10C(O)R13; â€”C(NR10)NR10R11; â€”C(NCN)NR10R11; â€”C(NCN)SR9; â€”NR10C(NCN)SR9; â€”NR10C(NCN)NR10R11; â€”NR10S(O)2R9; â€”S(O)mâ€²R9; â€”NR10C(O)C(O)NR10R11; â€”NR10C(O)C(O)R10; or R13; q is 0, 1, or 2; R12 is R13, OR14, OR15, SR14, S(O)mâ€²R7, S(O)2NR10R14, NR10R14, NR14C(O)R9, NR10C(Yâ€²)R14, NR10C(O)OR7, NR10C(Yâ€²)NR10R14, NR10S(O)2NR10R14, NR10C(NCN)NR10R14, NR10S(O)2R7, NR10C(CR4NO2)NR10R14, NR10C(NCN)SR9, NR10C(CR4NO2)SR9, NR10C(NR10)NR10R14, NR10C(O)C(O)NR10R14, or NR10C(O)C(O)OR14; or C3-C7 cycloalkyl, or (2-, 3- or 4-pyridyl), pyrimidinyl, pyrazolyl, (1- or 2-imidazolyl), pyrrolyl, piperazinyl, piperidinyl, morpholinyl, furanyl, (2- or 3-thienyl), quinolinyl, naphthyl, or phenyl, wherein each of (2-, 3- or 4-pyridyl), pyrimidinyl, pyrazolyl, (1- or 2-imidazolyl), pyrrolyl, piperazinyl, piperidinyl, morpholinyl, furanyl, (2- or 3-thienyl), quinolinyl, naphthyl, or phenyl may be substituted by OR14, OR15, SR14, S(O)mâ€²R7, S(O)2NR10R14, NR10R14, NR14C(O)R9, NR10C(Yâ€²)R14, NR10C(O)OR7, NR10C(Yâ€²)NR10R14, NR10S(O)2NR10R14, NR10C(NCN)NR10R14, NR10S(O)2R7, NR10C(CR4NO2)NR10R14, NR10C(NCN)SR9, NR10C(CR4NO2)SR9, NR10C(NR10)NR10R14, NR10C(O)C(O)NR10R14, or NR10C(O)C(O)OR14; R8 is independently selected from hydrogen or R9; R9 is C1-4 alkyl optionally substituted by one to three fluorines; R10 is OR8 or R11; R11 is hydrogen, or C1-4 alkyl unsubstituted or substituted by one to three fluorines; or when R10 and R11 are as NR10R11 they may together with the nitrogen form a 5 to 7 membered ring comprised of carbon or carbon and one or more additional heteroatoms selected from O, N, or S; R13 is oxazolidinyl, oxazolyl, thiazolyl, pyrazolyl, triazolyl, tetrazolyl, imidazolyl, imidazolidinyl, thiazolidinyl, isoxazolyl, oxadiazolyl, or thiadiazolyl, and each of these heterocyclic rings is connected through a carbon atom and each may be unsubstituted or substituted by one or two C1-2 alkyl groups unsubstituted or substituted on the methyl with 1 to 3 fluoro atoms; R14 is hydrogen or R7; or when R8 and R14 are as NR8R14 they may together with the nitrogen form a 5 to 7 membered ring comprised of carbon or carbon and one or more additional heteroatoms selected from O, N, or S; R15 is C(O)R14, C(O)NR8R14, S(O)qNR8R14 or S(O)qR7 where q is 0, 1 or 2; provided that: (f) R7 is not C1-4 alkyl unsubstituted or substituted by one to three fluorines; or the pharmaceutically acceptable salts thereof.