Polycyclic dihydrothiazoles having substituted alkyl radicals in the two-position, process for their preparation, and their use as pharmaceuticals

A compound of formula I:

• wherein:
• Y is selected from the group consisting of a direct bond, —CH2—, and —CH2—CH2—;
• X is selected from the group consisting of CH2, CH(CH3), CH(C2H5), CH(C3H7), and CH(C6H5);
• R1, R1′ are independently selected from the group consisting of H, F, Cl, Br, I, CF3, NO2, CN, COOH, COO(C1-C6)alkyl, CONH2, CONH(C1-C6)alkyl, CON[(C1-C6)alkyl]2, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkynyl, O—(C1-C6)-alkyl,
• wherein one or more of the hydrogens in the alkyl moieties may be optionally replaced by fluorine,
• or a hydrogen may be optionally replaced by OH, OC(O)CH3, OC(O)H, O—CH2—Ph, NH2, NH—CO—CH3 or N(COOCH2Ph)2,
• SO2—NH2, SO2NH(C1-C6)-alkyl, SO2N[(C1-C6)-alkyl]2, S—(C1-C6)-alkyl, S—(CH2)n-phenyl, SO—(C1-C6)-alkyl, SO—(CH2)n-phenyl, SO2—(C1-C6)-alkyl, SO2—(CH2)n-phenyl,
• where n is 0-6 and wherein the phenyl radical is optionally substituted in up to two positions by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1C6)-alkyl, (C1-C6)-alkyl, or NH2;
• NH2, NH—(C1-C6)-alkyl, N((C1-C6)-alkyl)2, NH(C1-C7)-acyl, phenyl, biphenyl, O—(CH2)n-phenyl, where n is 0-6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2-or 3-furanyl, 2- or 3-thienyl,
• wherein the phenyl, biphenyl, naphthyl, pyridyl, furanyl or thienyl rings may be independently optionally substituted up to 3 times by F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-6)-alkyl, NH2, NH(C1-C6)-alkyl, N((C1-C6)-alkyl)2, SO2—CH3, COOH, COO—(C1-C6)-alkyl, or CONH2;
• 1,2,3-triazol-5-yl, wherein the triazole ring may be optionally substituted in the 1-, 2- or 3-position by methyl or benzyl;
• and
• tetrazol-5-yl, wherein the tetrazole ring may be optionally substituted in the 1- or 2-position by methyl or benzyl;
• R2 is selected from the group consisting of H, (C1-6)-alkyl, (C3-C6)-cycloalkyl, (CH2)n′-phenyl, (CH2)n′-thienyl, (CH2)n′-pyridyl, (CH2)n′-furyl, C(O)—(C1-C6)-alkyl, C(O)—(C3-C6)-cycloalkyl, C(O)—(CH2)n′-phenyl, C(O)—(CH2)n′-thienyl, C(O)—(CH2)n′-pyridyl and C(O)—(CH2)n′-furyl, where n′ is 0-5,
• wherein the phenyl, thienyl, pyridyl, or furyl ring may be optionally substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl;
• R3 is selected from the group consisting of H, (C1-C6)-alkyl, F, CN, N3, O—(C1-C6)-alkyl, (CH2)n′-phenyl, (CH2)n′-thienyl, (CH2)n′-pyridyl and (CH2)n′-furyl, where n′ is 0-5,
• wherein the phenyl, thienyl, pyridyl, or furyl ring may be optionally substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl, (C2-C6)-alkynyl, (C2-C6)-alkenyl, C(O)OCH3, C(O)OCH2CH3, C(O)OH, C(O)NH2, C(O)NHCH3, C(O)N(CH3)2, or OC(O)CH3;
• R4 is selected from the group consisting of (C8-C6)-cycloalkyl,
• wherein one or more hydrogens of the alkyl moiety may be optionally replaced by fluorine,
• or a hydrogen may be optionally replaced by OH, OC(O)CH3, OC(O)H, O—CH2—Ph or O—(C1-C4)-alkyl;
• (CH2)n″—A—R8, where n″ is 1-6, except for when (CH2)n″—A—R8 is —CH2—O—CH2-phenyl, then the phenyl moiety is unsubstituted;
• and
• (CH2)r—B—R9, where r is 1-6;
• A is selected from the group consisting of O, S, SO and SO2;
• B is selected from the group consisting of NH, N—(C1-6)-alkyl, NCHO and N(CO—CH3);
• R8 is selected from the group consisting of (C5-C24)-alkyl, (C3-C10)-cycloalkyl,
• wherein one or more hydrogens of the alkyl radical may be optionally replaced by fluorine,
• or a hydrogen may be optionally replaced by OH, OC(O)CH3, OC(O)H, O—CH2—Ph or O—(C1-C4)-alkyl;
• and
• (CH2)m-aryl, where m is 0-6 and aryl is selected from the group consisting of phenyl, naphthyl, biphenyl, thienyl and pyridyl;
• wherein the aryl moiety may be optionally substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, S—(C1-C6)-alkyl, SO—(C1-C6)-alkyl, SO2—(C1-C6)-alkyl, SO2—NH2, SO2—NH(C1-C8-alkyl), SO2—N(C1-C8-alkyl)2, SO2—NH(C3-C8-cycloalkyl), SO2—N(C3-C8-cycloalkyl)2, (CH2)m′, —SO2—NH2, (CH2)m—SO2—NH—(C1-C6)-alkyl, (CH2)m′—SO2—N((C1-C6)-alkyl)2, where m′ is 1-6, SO2—N(═CH—N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO(C1-C6)alkyl, COO(C3-C6)cycloalkyl, CONH2, CONH(C1-C6)alkyl, CON[(C1-C6)alkyl]2, CONH(C3-C6)cycloalkyl, NH2, NH(C1-C6)-alkyl, N(C1-C6-alkyl)2, NH—CO—(C1-C6)-alkyl, NH—CO—phenyl, NH—SO2—(C1-C8-alkyl), N(C1-C6-alkyl)—SO2—(C1-C8-alkyl), NH—SO2-phenyl,
• wherein the phenyl ring may be optionally substituted up to two times by F, Cl, CN, OH, (C1-C6)-alkyl, O—(C1-C6)-alkyl, CF3, COOH, COO(C1-C6)-alkyl or CONH2,
• pyrrolidin-1-yl, morpholin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O—(CH2)p-phenyl, S—(CH2) p-phenyl or SO2—(CH2)p-phenyl, where p is 0-3;
• R9 is (CH2)m-aryl, where m is 0-6 and aryl is selected from the group consisting of phenyl, naphthyl, biphenyl, thienyl and pyridyl;
• wherein the aryl moiety may be optionally substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, S—(C1-6)-alkyl, SO—(C1-C6)-alkyl, SO2—(C1-C6)-alkyl, SO2—NH2, SO2—NH(C1-C8-alkyl), SO2—N(C1C8-alkyl)2, SO2—NH(C3-C8-cycloalkyl), SO2—N(C3-C8-cycloalkyl)2, (CH2)m′—SO2—NH2, (CH2)m—SO2—NH—(C1-C6)-alkyl, (CH2)m′—SO2—N((C1-C6)-alkyl)2, where m′ is 1-6, SO2—N(═CH—N(CH3)2), (C1-C6)-alkyl, (C3-C6)-cycloalkyl, COOH, COO(C1-C6)alkyl, COO(C3-C6)cycloalkyl, CONH2, CONH(C1-C6)alkyl, CON[(C1-C6)alkyl]2, CONH(C3-C6)cycloalkyl, NH2, NH(C1-C6)-alkyl, N(C1-C6-alkyl)2, NH—CO—(C1-C6)-alkyl, NH—CO—phenyl, NH—SO2—(C1-C8-alkyl), N(C1-C6-alkyl)—SO2—(C1-C8-alkyl), NH—SO2-phenyl,
• wherein the phenyl ring may be optionally substituted up to two times by F, Cl, CN, OH, (C1-C6)-alkyl, O—(C1-C6)-alkyl, CF3, COOH, COO(C1-C6)-alkyl or CONH2,
• pyrrolidin-1-yl, morpholin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, (CH2)p-phenyl, O—(CH2)p-phenyl, S—(CH2) p-phenyl or SO2—(CH2)p-phenyl, where p is 0-3;
• and a physiologically acceptable salt thereof.