8,8a-dihydroindeno[1,2-d]thiazole derivatives which carry in the 2-position a substituent having a sulfonamide structure or sulfone structure; processes for their preparation and their use as medicaments

A method for the prophylaxis or treatment of obesity comprising administering to a patient in need thereof one or more compounds of formula I:

• in which
• R1, R1′ are independently selected from 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 of the alkyl radicals may be replaced by fluorine, or one hydrogen may be 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,
• wherein n is 0-6 and the phenyl radical may be substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-C6)-alkyl or NH2;
• NH2, NH—(C1-C6)-alkyl, N[(C1-C6)-alkyl]2, NH—(CO)—(C1-C7)alkyl, phenyl, biphenylyl, O—(CH2)n-phenyl, where n is 0-6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl,
• wherein any of the phenyl, biphenyl, naphthyl, pyridyl, furanyl or thienyl rings may be substituted one to three times by F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-C6)-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 substituted in the 1-, 2- or 3-position by methyl or benzyl;
• or tetrazol-5-yl, where the tetrazole ring may be substituted in the 1- or 2 position by methyl or benzyl;
• R2 is H, (C1-C6)-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 or C(O)—(CH2)n-furyl,
• wherein n is 0-5 and in which any of phenyl, thienyl, pyridyl or furyl may be substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl;
• R3 is H, (C1-C6)-alkyl, F, CN, N3, O—(C1-C6)-alkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl (CH2)n-furyl,
• where n is 0-5 and in which phenyl, thienyl, pyridyl or furyl may be substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl;
• OC(O)CH3, (C2-C6)-alkynyl, (C2-C6)-alkenyl, COO(C1-C6)-alkyl, C(O)OH, C(O)NH2, C(O)NHCH3 or C(O)N(CH3)2;
• R4 is (CH2)n—R5, wherein n is 0-6;
• R5 is phenyl, biphenylyl, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-thienyl, 2- or 3-furyl, 2-, 4- or 5-thiazolyl, 2-, 4- or 5-oxazolyl, 1-pyrazolyl, 3- or 5-isoxazolyl, 2- or 3-pyrrolyl, 2- or 3-pyridazinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 2-(1,3,5-triazinyl), 2- or 5-benzimidazolyl, 2-benzothiazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, tetrazol-5-yl, indol-3-yl, indol-5-yl or N-methylimidazol-2-, -4- or -5-yl;
• and R5 is substituted by
• NH—SO2—(C1-C6)-alkyl or NH—SO2-phenyl,
• wherein the phenyl ring may be substituted up to two times by F, Cl, CN, OH, (C1-C6)-alkyl, O—(C1-C6)-alkyl, CF3, COOH, COO(C1-C6)-alkyl, CONH2, (CH2)n—SO2—(C1-C6)-alkyl, wherein n is 1-6, (CH2)m—SO2—NH2, (CH2)m—SO2—NH—(C1-C6)-alkyl, (CH2)m—SO2—N[(C1-C6)-alkyl]2 or (CH2)m—SO2—N(═CH—N(CH3)2), wherein m is 0-6;
• and R5 may be further substituted by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, S—(C1-C6)-alkyl, SO—(C1-C6)-alkyl, (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—CO—(C1-C6)-alkyl, NH—CO-phenyl, pyrrolidin-1-yl, morpholin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, (CH2)n-phenyl, O—(CH2)n-phenyl, S—(CH2)n-phenyl, SO2—(CH2)n-phenyl, wherein n is 0-3;
• and its physiologically acceptable salts and physiologically functional derivatives
• further comprising administering an additional anorectic active agent.

A method for the prophylaxis or treatment of type II diabetes comprising administering to a patient in need thereof one or more compounds of formula I:

• in which
• R1, R1′ are independently selected from 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 of the alkyl radicals may be replaced by fluorine, or one hydrogen may be 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,
• wherein n is 0-6 and the phenyl radical may be substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-C6)-alkyl or NH2;
• NH2, NH—(C1-C6)-alkyl, N[(C1-C6)-alkyl]2, NH—(CO)—(C1-C7)alkyl, phenyl, biphenylyl, O—(CH2)n-phenyl, where n is 0-6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl,
• wherein any of the phenyl, biphenyl, naphthyl, pyridyl, furanyl or thienyl rings may be substituted one to three times by F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-C6)-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 substituted in the 1-, 2- or 3-position by methyl or benzyl;
• or tetrazol-5-yl, where the tetrazole ring may be substituted in the 1- or 2 position by methyl or benzyl;
• R2 is H, (C1-C6)-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 or C(O)—(CH2)n-furyl,
• wherein n is 0-5 and in which any of phenyl, thienyl, pyridyl or furyl may be substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl;
• R3 is H, (C1-C6)-alkyl, F, CN, N3, O—(C1-C6)-alkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl (CH2)n-furyl,
• where n is 0-5 and in which phenyl, thienyl, pyridyl or furyl may be substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl;
• OC(O)CH3, (C2-C6)-alkynyl, (C2-C6)-alkenyl, COO(C1-C6)-alkyl, C(O)OH, C(O)NH2, C(O)NHCH3 or C(O)N(CH3)2;
• R4 is (CH2)n—R5, wherein n is 0-6;
• R5 is phenyl, biphenylyl, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-thienyl, 2- or 3-furyl, 2-, 4- or 5-thiazolyl, 2-, 4- or 5-oxazolyl, 1-pyrazolyl, 3- or 5-isoxazolyl, 2- or 3-pyrrolyl, 2- or 3-pyridazinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 2-(1,3,5-triazinyl), 2- or 5-benzimidazolyl, 2-benzothiazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, tetrazol-5-yl, indol-3-yl, indol-5-yl or N-methylimidazol-2-, -4- or -5-yl;
• and R5 is substituted by
• NH—SO2—(C1-C6)-alkyl or NH—SO2-phenyl,
• wherein the phenyl ring may be substituted up to two times by F, Cl, CN, OH, (C1-C6)-alkyl, O—(C1-C6)-alkyl, CF3, COOH, COO(C1-C6)-alkyl, CONH2, (CH2)n—SO2—(C1-C6)-alkyl, wherein n is 1-6, (CH2)m—SO2—NH2, (CH2)m—SO2—NH—(C1-C6)-alkyl, (CH2)m—SO2—N[(C1-C6)-alkyl]2 or (CH2)m—SO2—N(═CH—N(CH3)2), wherein m is 0-6;
• and R5 may be further substituted by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, S—(C1-C6)-alkyl, SO—(C1-C6)-alkyl, (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—CO—(C1-C6)-alkyl, NH—CO-phenyl, pyrrolidin-1-yl, morpholin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, (CH2)n-phenyl, O—(CH2)n-phenyl, S—(CH2)n-phenyl, SO2—(CH2)n-phenyl, wherein n is 0-3;
• and its physiologically acceptable salts and physiologically functional derivatives,
• further comprising administering an additional anorectic agent.

A method for enhancing lipid metabolism comprising administering to a patient in need thereof one or more compounds of formula I:

• in which
• R1, R1′ are independently selected from 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 of the alkyl radicals may be replaced by fluorine, or one hydrogen may be 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,
• wherein n is 0-6 and the phenyl radical may be substituted up to two times by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-C6)-alkyl or NH2;
• NH2, NH—(C1-C6)-alkyl, N[(C1-C6)-alkyl]2, NH—(CO)—(C1-C7)alkyl, phenyl, biphenylyl, O—(CH2)n-phenyl, where n is 0-6, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl or 2- or 3-thienyl,
• wherein any of the phenyl, biphenyl, naphthyl, pyridyl, furanyl or thienyl rings may be substituted one to three times by F, Cl, Br, I, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, (C1-C6)-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 substituted in the 1-, 2- or 3-position by methyl or benzyl;
• or tetrazol-5-yl, where the tetrazole ring may be substituted in the 1- or 2 position by methyl or benzyl;
• R2 is H, (C1-C6)-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 or C(O)—(CH2)n-furyl,
• wherein n is 0-5 and in which any of phenyl, thienyl, pyridyl or furyl may be substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl;
• R3 is H, (C1-C6)-alkyl, F, CN, N3, O—(C1-C6)-alkyl, (CH2)n-phenyl, (CH2)n-thienyl, (CH2)n-pyridyl (CH2)n-furyl,
• where n is 0-5 and in which phenyl, thienyl, pyridyl or furyl may be substituted up to two times by Cl, F, CN, CF3, (C1-C3)-alkyl, OH or O—(C1-C6)-alkyl;
• OC(O)CH3, (C2-C6)-alkynyl, (C2-C6)-alkenyl, COO(C1-C6)-alkyl, C(O)OH, C(O)NH2, C(O)NHCH3 or C(O)N(CH3)2;
• R4 is (CH2)n—R5, wherein n is 0-6;
• R5 is phenyl, biphenylyl, 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-thienyl, 2- or 3-furyl, 2-, 4- or 5-thiazolyl, 2-, 4- or 5-oxazolyl, 1-pyrazolyl, 3- or 5-isoxazolyl, 2- or 3-pyrrolyl, 2- or 3-pyridazinyl, 2-, 4- or 5-pyrimidinyl, 2-pyrazinyl, 2-(1,3,5-triazinyl), 2- or 5-benzimidazolyl, 2-benzothiazolyl, 1,2,4-triazol-3-yl, 1,2,4-triazol-5-yl, tetrazol-5-yl, indol-3-yl, indol-5-yl or N-methylimidazol-2-, -4- or -5-yl;
• and R5 is substituted by
• NH—SO2—(C1-C6)-alkyl or NH—SO2-phenyl,
• wherein the phenyl ring may be substituted up to two times by F, Cl , CN, OH, (C1-C6)-alkyl, O—(C1-C6)-alkyl, CF3, COOH, COO(C1-C6)-alkyl, CONH2, (CH2)n—SO2—(C1-C6)-alkyl, wherein n is 1-6, (CH2)m—SO2—NH2, (CH2)m—SO2—NH—(C1-C6)-alkyl, (CH2)m—SO2—N[(C1-C6)-alkyl]2 or (CH2)m—SO2—N(═CH—N(CH3)2), wherein m is 0-6;
• and R5 may be further substituted by F, Cl, Br, OH, CF3, NO2, CN, OCF3, O—(C1-C6)-alkyl, S—(C1-C6)-alkyl, SO—(C1-C6)-alkyl, (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—CO—(C1-C6)-alkyl, NH—CO-phenyl, pyrrolidin-1-yl, morpholin-1-yl, piperidin-1-yl, piperazin-1-yl, 4-methylpiperazin-1-yl, (CH2)n-phenyl, O—(CH2)n-phenyl, S—(CH2)n-phenyl, SO2—(CH2)n-phenyl, wherein n is 0-3;
• and its physiologically acceptable salts and physiologically functional derivatives
• further comprising administering an additional anorectic active agent.