GB1374769A - Triazoloquinazoline derivatives - Google Patents

Abstract

1374769 Triazoloquinazoline derivatives SANDOZ Ltd 13 Sept 1971 [16 Sept 1970] 42528/71 Heading C2C The invention comprises novel triazoloquinazoline derivatives of the Formula I wherein either (a) n is 0, 1, 2 or 3, R is F, Cl, Br, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, NO 2 or CF 3 , provided that (i) when n is 2 or 3, the radicals R may be the same or different, (ii) when n is 2 or 3 each R is other than NO 2 or CF 3 , (iii) when n is 3, R is C 1 -C 2 alkoxy, or (b) when n is 2 and R's are on adjacent carbon atoms together may be methylenedioxy, and either P is N, Q is =C 11 and R 1 is OR 7 , wherein R 7 is C 1 -C 6 alkyl, allyl, methyallyl, propargyl or -Z-N(R 8 )R 9 , in which Z is C 1 -C 4 alkylene, and R 8 and R 9 each are C 1 -C 3 alkyl, or P is =CH, Q is N and R 1 is -N(R 10 )R 11 , in which R 10 is H and R 11 is C 1 -C 5 alkyl, allyl, methylallyl, propargyl or Z-N(R 8 )R 9 , or R 10 and R 11 together with N atom to which they are attached form di-(C 1 -C 3 alkyl)amino, diallylamino, di. methylallylamino, dipropargylamino, 1- pyrrolidinyl, piperidino, morpholino, 1-piperazinyl or 4-(C 1 -C 2 alkyl)-1-piperazinyl, or compounds of Formula VI wherein Y is Cl or Br, and addition salts thereof. Compounds of Formula I above in which P is = CH, Q is N and R 1 is N(R 10 )R 11 are prepared by reacting compounds of Formula VI with compounds of the formula HN(R 9 )R 10 or by reacting compounds of the Formula IX with compounds of the formula in which m is 0 or 1 under substantially anhydrous conditions. Compounds of Formula I above in which P is N, Q is =CH and R 1 is OR, are obtained by reacting compounds of Formula VI above with compounds of the formula MOR 7 , in which M is H, or alkali metal or alkaline earth metal cation, the process being carried out when M is H in the presence of inert organic bases or under anhydrous conditions in the presence of inorganic bases and, when M is other than H, in the presence of a solvent. Compounds of Formula VI above are made by reacting the appropriate 2-chloro (or 2-bromo)-4-hydrazinoquinazolines with compounds of the formula CH[O(CH 2 ) m CH 3 ] 3 , wherein m is 0 or 1, under substantially anhydrous conditions. 6,7 - Dimethoxy - 2 - chloro - 4 - hydrazinoquinazoline is obtained by reacting 2,4-dichloro- 6,7-dimethoxyquinazoline with hydrazine. 4 - Hydrazino - 2 - (4 - methyl - 1 - piperazinyl)- 8,9-dimethoxyquinazoline is made by reacting 2 - chloro - 4 - hydrazino - 6,7 - dimethoxyquinazoline with 1-methylpiperazine. Pharmaceutical compositions, suitable for oral or parenteral administration, contain the above novel compounds or pharmaceutically acceptable acid addition salts thereof in association with diluents and carriers. The compounds possess hypotensive, anti-hypertensive and anti-inflammatory activities.