Patent CA-2125104-A1 (CA)
Title: Substituted benzoylguanidines, process for their preparation, their use as a medicament or diagnostic, and medicament containing them
Inventor: SCHWARK JAN-ROBERT
IPC: C07D213/30
Filed: 1994-06-03
Abstract: Benzoylguanidines of the formula I   (see formula I) are described in which:      R(1) is R(6) -CO or R(7)R(8)N-CO, with R(6), R(7) and R(8) being (perfluoro)alk(en)yl or -(CH)2n-R(9), R(9) being cycloalkyl, phenyl, biphenylyl or naphthyl, where R(7) and R(8) can together be 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl;        R(2) is defined as R(1), or is H, Hal, CN, NO2, (perfluoro)alk(en)yl or -(CH)2R(15) with R(15) being cycloalkyl, phenyl, biphenylyl or naphthyl, or R(2) is (C1-C9)-heteroaryl, or R(2) is SR(18), -OR(18), -NR(18)R(19) or -CR(18)R(19)R(20);      R(18) is - (CH2)-heteroaryl, R(19) and R(20) are defined as R(18) or are H or (perfluoro)alkyl, or R(2) is R(21)-SO m or R(22)R(23)N-SO2-, with R(21) being (perfluoro)alk(en)yl or -CH2-R(24), R(24) being cycloalkyl, phenyl, biphenylyl or naphthyl, R(22) being H, (perfluoro)alk(en)yl or -(CH2)n-R(29), R(29) being (C3-C8)-cycloalkyl, phenyl, biphenylyl or naphthyl, R(23) being H or (perfluoro)alkyl, where R(22) and R(23) can together be 4 or 5 methylene groups of which one CH2 group can be replaced by oxygen, S, NH, N-CH3 or N-benzyl; or R(2) is R(33)X-, where X is oxygen, S. NR(34), (D=O)A- or NR(34)C=MN(*)R(35)-, with M being oxygen or S, A being oxygen or NR(34), D being C or SO      R(33) and R(35) being (perfluoro)alk(en)yl or -(CH2)n-R(36), where R(36) is cycloalkyl, phenyl, biphenylyl or naphthyl, R(34) being H or (perfluoro)alkyl, where A and N(*) are banded to the phenyl nucleus of the benzoylguanidine parent substance; or R(2) is -SR(40), -OR(40), -NHR(40), -NR(40)R(41), -CHR(40)R(42), (see formula II) -C.ident.CR(45), (see formula III, IV) where R(40) and R(41) are identical or different and are -(CH2)p-(CHOH)q-(CH2)r-(C8 OH)t R(51) or -(CH2)p-O-(CH2-CH2O)q-R(51), R(51) is hydrogen or methyl, R(42) and R(43) are hydrogen or alkyl, or, together with the carbon atom carrying them, form a (C3-C8)-cycloalkyl;      R(44) is H, (C1-C6)-alkyl, (C3-C8)-cycloalkyl or -C e H2e -R(45) with R(45) being phenyl, heteroaryl or alkyl, R(46), R(47), R(48), R(49) and R(50) are hydrogen or methyl; or R(2) is R(55) -NH-SO2-, R(3), R(4) and R(5) are, independently of each other, defined as R(1) or R(2); and pharmaceutically tolerated salts thereof. Compounds I are suitable as antiarrhythmic pharmaceuticals having a cardioprotective component for infarct prophylaxis and infarct treatment and for the treatment of angina pectoris, where they also preventively inhibit or greatly reduce the pathophysiological processes in the formation of is chemically-induced damage. Compounds I are moreover distinguished by powerful inhibitory action on cell proliferation. They can therefore be used as antiatherosclerotics, agents against diabetic late complications, cancers, fibrotic disorders, pulmonary fibrosis, hepatic fibrosis or renal fibrosis, organ hypertrophies and hyperplasias. They are active inhibitors of the cellular sodium-praton antiporter (Na+/H+ exchanger).