ANTISECRETORY BRANCHED-CHAIN HETEROCYCLIC GUANIDINE DERIVATIVES, PROCESSES FOR THEIR MANUFACTURE, INTERMEDIATES, AND PHARMACEUTICAL COMPOSITIONS CONTAINING SAID DERIVATIVES

摘要

Heterocyclic guanidine derivatives of the formula: in which D is O,S or NH; E is CH or when D is O or S, E is N; Y is S, O, CH2, SO or a direct bond; P is a direct bond or C(1-4)unbranched alkylene optionally substituted by 1 or 2 C(1-4)alkyls and Q is C(1-4)unbranched alkylene optionally substituted by 1 or 2 C(1-4)alkyls, provided total number of alkyls in P and Q is 1 or 2, that when Y is S, O or SO, P is alkylene and that when Y is O or SO, Q is C(2-4)alkylene; R<1> is H or C(1-10)alkyl; A is 3,4-dioxocyclobuten-1,2-diyl or C = Z where Z is S, O, NCN, NNO2, CHNO2, NCONH2, C(CN)2, NCOR<2>, NCO2R<2>, NSO2R<2> or NR<3> where R<3> is C(1-6)alkyl or C(6-12)aryl and R<3> is H or C(1-6)alkyl; B is C(1-6)alkoxy, C(1-6)alkylthio or NR<4>R<5> where R<4> and R<5> are H, C(1-10)alkyl, C(3-6)alkenyl, C(3-6)alkynyl, C(2-6)(primary OH)alkyl, C(2-6)(primary NH2)alkyl, C(3-6)cycloalkyl, or R<4> and R<5> together are a 5- or 6-membered saturated ring which may contain an additional O or NH-: and the salts thereof. A process for the manufacture of said compounds is described; e.g. 2-guanidino-4-(5-amino-2-methylpentyl)-thiazole gives by reaction with dimethyl(cyanimido)dithiocarbonate and then methylamine 2-guanidino-4[5-(2-cyano-3-methylguanidino)-2-methylpentyl]thiazole.