Use of new and known sulphonyl guanazine cpds.

摘要

The use of sulphonyl guanazine cpds. of formula (I), and their salts and tautomers, is claimed for the prepn. of pharmaceuticals for treating metabolic disorders. A, D = H, 1-3C alkyl or 1-3C alkoxy; R1, R2 = 6-10C aryl, benzyl or Het (all opt. ring-substd. by upto 5 of halo, OCF3, CF3, OCHF2, phenyl, 1-7C alkoxy, 1-7C alkylthio, 1-7C alkoxycarbonyl, OH, COOH, 1-8C alkyl (opt. substd. by carboxy or 1-5C alkoxycarbonyl), opt. halo-substd. benzoyl, CONR4R5, NR6R7, SO2R8 or SO2NR9R10) or 1-15C alkyl; R3 = H or SO2R11; R4-R7 = H, 1-4C acyl, phenyl, or 1-5C alkyl (opt. substd. by phenyl (opt. substd. by CF3 or halo)); R8, R11 = 1-6C alkyl, benzyl or 6-10C aryl (opt. substd. by up to 5 of OH, phenyl, halo or 1-3C alkyl); R9, R10 = 1-6C alkyl or 1-6C alkoxy; and Het = 5 or 6 membered heterocycle contg. N, O and/or S, opt. benzo-fused. Over 70 cpds. (I) are new. They have formula (I) with the following substits. (1) A, D = Me; R3 = H; R1 = a gp. of formula (g); and R2 = (2-bromophenyl)methyl; (2) A, D = Me; R3 = H; R1 = a gp. of formula (h); and R2 = 2-bromophenyl or 2-chlorophenyl; (3) A, D = Me; R3 = H; R1 = a gp. of formula (a); R2 = pentafluoro phenyl, 2-substd. phenyl (where the substits. are Br or OCF3), 3-chlorophenyl, naphth-2-yl, 4-substd.-phenyl (where the substits. are Me, Br, t-Bu, Cl, phenyl or I), n-propyl, (CH2)11CH3, 2,4,5-trichlorophenyl, 4-chlorobenzyl, 7-quinolinyl, 2,3-dimethylphenyl, 4-chloro-2-trifluoromethyl-phenyl, 3,4-dimethylphenyl, or a gp. of formula (a1)-(a4); (4) A, D = OMe, R3 = H, R1 = a gp. of formula (b); and R2 = 2-substd. phenyl (where the substits. are OMe, Cl, F, Br, CF3 or SO2NMe2; (5) A, D = OMe, R1 = (a); R3 = H; R2 = 2,6-dichlorophenyl; (6) A, D = OMe; and R1 = (c1), R2 = 4-trifluoromethoxy phenyl and R3 = H; or R1 = (c2), R2 = trifluoromethoxy phenyl and R3 = (c3). (7) A = D = Me or OMe, R1 = a gp. of formula (d); R3 = H; R2 = (a); (8) A, D = Me, R1 = (b), R3 = H; R2 = 4-methyl phenyl, 2-substd. phenyl (where the substits. are OCF3, CF3, F or SO2NMe2 or 2-(methoxycarbonyl)benzyl; (9) A, D = Me, R1 = 2-fluorophenyl, R3 = H and R2 = (a5) or 2-carboxyphenyl; (10) A = OMe; D = Me, R1 = a gp. of formula (f); R2 = 4-methylphenyl and R3 = 4-methylphenylsulphonyl; (11) A, D = Me; R1 = (f), R3 = H; and R2 = 2-substd. phenyl (where the substits. are OCHF2, CF3 or OCH3); (12) A, D = OMe; R1 = gp. of formula (k), R3 = H; R2 = 2-chloro, 2-trifluoromethoxyphenyl or 2- or 3-difluoromethoxy phenyl; (13) A, D = Me; R1 = (a); and R3 = SO2R2, where R2 = n-Pr, 4-biphenyl, 4-chlorobenzyl, 4-iodophenyl, 3- or 4-chlorophenyl, 2,3-dimethylphenyl, (a2), 2- or 4-bromophenyl, pentafluorophenyl, 1- or 2-naphthyl or 4-t-butyl-phenyl; (14) A, D, R3 = H; R1 = (a), R2 = 2-bromophenyl; (15) A = Me; D = OMe; R1 = a gp. (l); R2 = 2-chlorophenyl and R3 = H; (16) A = Me; D = R3 = H; R1 = (a); and R2 = 4-methylphenyl; (17) A = D + Me; R1 = a gp. (m); R2 = 4-methylphenyl and R3 = H.