Bis-ortho-substituted benzoylguadines process for their preparation, their application as medicine or diagnosis as well as medicine containing them

摘要

Bis-ortho-substituted benzoyl-guanidines (I) and their salts are new: R1-R3 = R10-SOa-; R14R15N-SO2-; SR21; OR22; NR23R24; CR25R26R27; H; F; Cl; Br; I; CN; -(Xa)dg-CdaH2da+1; -(Xb)dh-(CH2)db-CdeF2de+1; 3-8C alkenyl; -CdfH2dfR30; NR40R41; -(Xe)-(CH2)ebR45; -CHR52R53; or -C(OH)R55R56; R4, R5 = 1-4C alkyl; 1-4C alkoxy; OH; F; Cl; Br; I; CN; or -On-(CH2)o-(CF2)p-CF3; a = 0-2; da = 0-8; db, df = 0-4; de = 0-7; dg, dh = 0 or 1; eb = 0-4; n = 0 or 1; o, p = 0-2; R10, R14, R15 = 1-8C alkyl; 1-8C perfluoroalkyl; 3-6C alkenyl; or -CabH2ab-R16; or R14 and R15 are both H; or R14+R15 = tetra- or pentamethylene with 1 CH2 optionally replaced by O, S or NQ; Q = H; Me or benzyl; ab = 0-4; R16 = 3-7C cycloalkyl or Ph optionally mono-, di- or trisubstituted by F, Cl, CF3, Me, OMe or NR17R18; R17, R18 = H; CF3; or 1-4C alkyl; R21-R23 and R25 = -CbH2b-(1-9C)-heteroaryl optionally mono-, di- or trisubstituted by F, Cl, CF3, Me, OMe, OH, NH2, NHMe or NMe2; b = 0-2; R24, R26, R27 = H; 1-4C alkyl; or 1-4C perfluoroalkyl; Xa = O; S; or R33; Xb = O; S; or NR34; R33, R34 = H; 1-4C alkyl; or 1-4C perfluoroalkyl; R30 = 3-8C cycloalkyl; or Ph, biphenylyl or naphthyl optionally mono-, di- or trisubstituted by F, Cl, CF3, Me, OMe or NR31R32; R31, R32 = H; 1-4C alkyl; or 1-4C perfluoroalkyl; R40, R41 = H; 1-8C alkyl; 1-8C perfluoroalkyl; or (CH2)e-R42; or R40+R41 = tetra- or pentamethylene with 1 CH2 optionally replaced by O, S or NQ; e = 0-4; R42 = 3-7C cycloalkyl or Ph optionally mono-, di- or trisubstituted by F, Cl, CF3, Me, OMe or NR43R44; R43, R44 = H; CF3; or 1-4C alkyl; Xe = O; S; or NR47; R47 = H; 1-4C alkyl; or 1-4C perfluoroalkyl; R45 = 3-7C cycloalkyl or Ph optionally mono-, di- or trisubstituted by F, Cl, CF3, Me, OMe, NR50R51 or -(Xfa)-(CH2)ed-(Xfb)R46; Xfa = CH2; O; S; or NR48; Xfb = O; S; or NR49; R46 and R48-R51 = H; 1-4C alkyl; or 1-4C perfluoroalkyl; ed = 1-4; R52 = -(CH2)g-(CHOH)h-(CH)i-(CHOH)k-R54 or -(CH2)g-O-(CH2-CH2O)h-R54; R53 = H or 1-4C alkyl; R54 = H or Me; g, h, i = 0-4; k = 1-4; R55 = H; 1-4C alkyl; or CH2OH; R56 = H or 1-4C alkyl; or R55+R56 = 3-6C cycloalkyl.