New 3-amino-6-chloro:pyrazine 2-carboxamide derivs. - useful as hypotensive, mucolytic, diuretic and antitumoural drugs

摘要

3,5-Diamino-6 -chloropyrazine cpds. of formula (I) and their acid addn. salts are new. In (I), R1 is H or 1-8C alkyl; R2 is morpholino; 1-8C alkyl (opt. substd. by opt. substd. heterocycle; phenyl opt. substd. by 1 or more 1-4C alkoxy (themselves opt. substd. by OH or NR7R8); CONR7R8; one or more of 1-4C alkoxy, OH, 1-4C hydroxyalkyl or phenoxy (itself opt. substd. by one or more F, Cl, CN, 1-4C alkyl or alkoxy or 1-4C alkoxy(1-4C)alkyl); or NR9R10), or R2 is 4-piperidinyl opt. 1-substd. by the acyl residue of an aliphatic, alicyclic, aromatic or hetero-aromatic carboxylic acid or by 1-8C alkyl opt. substd. by OH, phenoxy (opt. substd. by 1-4C alkoxy or 1-4C alkoxy (1-4C)alkyl) or 1-naphthoxy; or R2 = -C(=NH)-NHR11; R1 and R2 may together complete a piperidine or piperazine ring, opt. N-substd. by a heterocycle; acyl residue (as above) or 1-8C alkyl (opt. substd. by OH, phenoxy (opt substd. by 1-4C alkoxy or 1-4C alkoxy (1-4C) alkyl) or 1-naphthoxy); R7 and R8 are H or 1-4C alkyl; R9 and R10 are H; mono- or polycyclic heterocycle (opt. substd.); phenyl (opt. substd. by 1 or more of F, Cl, 1-4C alkyl and sulphonamido); acyl residue of a heterocycle contg. N or O atoms; di- or tri-chlorophenylsulphonyl substd. by amino; or 1-4C alkyl opt. substd by OH or phenyl (itself opt. substd. by 1 or more F, Cl, OH, 1-4C alkyl or 1-4C alkoxy (1-4C)alkyl) or R9 and R10 together complete morpholino; R11 = phenyl opt. substd by 1 or more F, Cl or 1-4C alkyl; unless specified, heterocyclic residues may contain N1O or S aotms and R3-R6 are H, 1-8C alkyl or benzyl. USE - (I) have antihypertensive, mucolytic, diuretic, carcinostatic and PAF-antagonising activities; among other things they inhibit Na(+)/proton and Na(+)/hi(+) exchanges. (I) are also intermediates for other pharmaceuticals. The pref. unit doses contain 20-100mg (I), in usual tablets, capsules, injection solns., etc.