Patent ID: 6043248
Filing Date: 2000-03-28
Classification: A61P,C07D

Abstract:
A compound of the following formula: where m is 0 or 1;R.sup.1 is selected from the group consisting of --C.tbd.CH, --CO.sub.2 R.sub.53, --CONR.sub.54 R.sub.55, ##STR13## where s is 0 or 1 and R.sub.20, R.sub.21, R.sub.22, R.sub.23, R.sub.24, and R.sub.25 are the same or different and are selected from --H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkenyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, --C.sub.3 -C.sub.8 cycloalkyl, --CF.sub.3, --NO.sub.2, -halo, --OH, --CN, phenyl, phenylthio, -styryl, --CO.sub.2 (R.sub.31), --CON(R.sub.31)(R.sub.32), --CO(R.sub.31), --(CH.sub.2).sub.n --N(R.sub.31)(R.sub.32), --C(OH)(R.sub.31)(R.sub.33), --(CH.sub.2).sub.n N(R.sub.31)(CO(R.sub.33)), (CH.sub.2).sub.n N(R.sub.31)(SO.sub.2 (R.sub.33)), or R.sub.20 and R.sub.21, R.sub.21 and R.sub.22, or R.sub.22 and R.sub.23 are taken together to form a five or six-membered saturated or unsaturated ring containing 0 or 1 oxygen, nitrogen or sulfur, where the unsaturated ring may be optionally substituted with 1, 2 or 3, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --OH, --CH.sub.2 OH, --(CH.sub.2).sub.n --N(R.sub.31)(R.sub.32), --C.sub.3 -C.sub.8 cycloalkyl, --CF.sub.3, -halo, --CO.sub.2 (R.sub.31), --CON(R.sub.31)(R.sub.32), --CO(R.sub.31), --(CH.sub.2).sub.n N(R.sub.31)(CO(R.sub.33)), --(CH.sub.2).sub.n N(R.sub.31)(SO.sub.2 (R.sub.33)), --CN, --CH.sub.2 CF.sub.3 or --CH(CF.sub.3).sub.2, or phenyl, and the saturated ring may be optionally substituted with 1, 2 or 3, --C.sub.1 -C.sub.6 alkyl, --C.sub.1 -C.sub.6 alkoxy, --OH, --CH.sub.2 OH or --(CH.sub.2).sub.n --N(R.sub.31)(R.sub.32) or one oxo (.dbd.O);where n is 0-3 and R.sub.31, R.sub.32, and R.sub.33 are the same or different and are selected from--H,C.sub.1 -C.sub.6 alkyl,phenyl optionally substituted with 1, 2, or 3 -halo, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, --OH or --CN,or where R.sub.31 and R.sub.32 taken together with the attached nitrogen to form a ring selected from -pyrrolidinyl, -piperidinyl, -4-morpholinyl, -4-thiomorpholinyl, -4-piperazinyl, -4-(1-C.sub.1 -C.sub.6 alkyl)piperazinyl, or a member selected from the group consisting of: 1-cyclohexenyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-imidazolyl, 4-imidazolyl, 2-benzothiazolyl, 2-benzoxazolyl, 2-benzimidazolyl, 2-oxazolyl, 4-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 5-methyl-3-isoxazolyl, 5-phenyl-3-isoxazolyl, 4-thiazolyl, 3-methyl-2-pyrazinyl, 5-methyl-2-pyrazinyl, 6-methyl-2-pyrazinyl, 5-chloro-2-thienyl, 3-furyl, benzofuran-2-yl, benzothien-2-yl, 2H-1-benzopyran-3-yl, 2,3-dihydrobenzopyran-5-yl, 1-methylimidazol-2-yl, quinoxalin-2-yl, piperon-5-yl, 4,7-dichlorobenzoxazol-2-yl, 4,6-dimethyl-pyrimidin-2-yl, 4-methylpyrimidin-2-yl, 2,4-dimethylpyrimidin-6-yl, 2-methylpyrimidin-4-yl, 4-methylpyrimidin-6-yl, 6-chloropiperon-5-yl, 5-chloroimidazo[1,2-a]pyridin-2-yl, 1H-inden-3-yl, 1-H-2-methyl-inden-2-yl, 3,4-dihydronaphth-1-yl, S-4-isopropenylcyclohexen-1-yl or 4-dihydronaphth-2-yl;where R.sub.53 is selected from the group consisting of --H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, phenyl (optionally substituted with 1, 2, or 3 -halo, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, --OH, --CN), or a five or six-membered unsaturated ring containing 0 or 1 oxygen, nitrogen or sulfur, where the unsaturated ring may be optionally substituted with --H, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --OH, --CH.sub.2 OH, or --(CH.sub.2).sub.n --N(R.sub.31)(R.sub.32);where R.sub.54 and R.sub.55 being the same or different are selected from --H, C.sub.1 -C.sub.6 alkyl, allyl, or phenyl (optionally substituted with 1, 2, or 3 -halo, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or --CF.sub.3), or taken together with the attached nitrogen to form a ring selected from -pyrrolidinyl, -piperidinyl, -4-morpholinyl, -4-thiomorpholinyl, -4-piperazinyl, -4-(1-C.sub.1 -C.sub.6 alkyl)piperazinyl;R.sub.41 and R.sub.42, being the same or different, are selected from the group consisting of --H and C.sub.1 -C.sub.4 alkyl;R.sub.12 is selected from the group consisting of --H, C.sub.1 -C.sub.6 alkyl, --C.sub.3 -C.sub.6 cycloalkyl, --CN, --C(O)NH.sub.2, --C(O)N(C.sub.1 -C.sub.6 alkyl)(C.sub.1 -C.sub.6 alkyl), --CO.sub.2 H, --CO.sub.2 (C.sub.1 -C.sub.6 alkyl), --CH.sub.2 OH, --CH.sub.2 NH.sub.2 or --CF.sub.3 ;R.sub.13 is selected from the group consisting of --H, C.sub.1 -C.sub.6 alkyl or --CF.sub.3 ;Y is selected from --S--, --S(O)--, --S(O).sub.2, or --O--;R.sub.4 is selected from the group consisting of --H, --OH, halo or --NR.sub.15 R.sub.16 where R.sub.15 is --H and R.sub.16 is --H, C.sub.1 -C.sub.6 alkyl, --NH.sub.2 or R.sub.15 and R.sub.16 taken together with the --N form 1-pyrrolidino, 4-morpholino or 1-piperidino;R.sub.5 is selected from the group consisting of --H, --C.sub.2 H.sub.4 OH, --C.sub.2 H.sub.4 --O--TBDMS, halo, --C.sub.3 --C.sub.6 cycloalkyl, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.3 alkoxy;R.sub.6 is selected from the group consisting of --H, --OH, halo, --CN, --CF.sub.3, --CO.sub.2 (R.sub.61), --C(O)R.sub.61 or --C(O)N(R.sub.61)(R.sub.62) where R.sub.61 and R.sub.62 are the same or different and are selected from --H, C.sub.1 -C.sub.6 alkyl, phenyl optionally substituted with 1, 2, or 3-halo, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, --CF.sub.3, --OH, --CN, or where R.sub.61 and R.sub.62 taken together with the attached nitrogen to form a ring selected from -pyrrolidinyl, -piperidinyl, -4-morpholinyl, -4-thiomorpholinyl, -4-piperazinyl, or -4-(C.sub.1 -C.sub.6 alkyl)piperazinyl; and pharmaceutically acceptable salts, hydrates, N-oxides and solvates thereof;with the following provisos:(1) that R.sub.4 and R.sub.6 are not both --H;(2) that R.sub.12 and R.sub.13 are not both --H except when R.sub.6 is selected from --CN, --CF.sub.3, --CO.sub.2 (R.sub.61), --C(O)R.sub.61 or --C(O)N(R.sub.61)(R.sub.62), or R.sub.1 is selected from --CO.sub.2 R.sub.53 or C(O)N(R.sub.54)(R.sub.55);(3) that when m is 0, Y is --S-- or --S(O)--, R.sub.13 is --H, R.sub.12 is --H or C.sub.1 -C.sub.4 alkyl, R.sub.4 is --H, --OH, halo or NH.sub.2, R.sub.5 is --H, halo or C.sub.1 -C.sub.4 alkyl and R.sub.6 is from the group consisting of --H, halo or --OH, then R.sup.1 is not 2- or 3-pyridinyl optionally substituted with C.sub.1 -C.sub.4 alkyl, a halogen atom, NH.sub.2 or --OH, and;(4) that R.sub.1 is not --CONR.sub.54 R.sub.55 when m is 0 and R.sub.6 is H; and(5) the compounds are other than4-amino-6-chloro-2-(1-(4-(4-morpholinylcarbinyl)-2-pyridinyl)-ethyl)thio-py rimidine and4-amino-6-chloro-2-(1-(4-methyl-2-pyridyl)pentyl)thio-pyrimidine.