GB1348088A - Nitrofuran and nitrothiophene derivatives - Google Patents

Abstract

1348088 Nitrofuran and nitrothiophene derivatives BOEHRINGER MANNHEIM GmbH 24 Oct 1972 [29 Oct 1971] 48937/72 Addition to 1318013 Heading C2C Novel compounds of Formula I (in which X is S or O, Het is atriazolopyridazine or thiadiazole system and R is an acylamino, acylaminoalkylamino, carbalkoxyalkylamino or cycloalkylamino radical or a piperidino or 1- piperazinyl radical substituted in the 4-position by a hydroxyl or hydroxyalkyl group) and pharmacologically acceptable acid addition salts thereof, are prepared by (a) reacting a compound of Formula II (in which R 1 is C 1-6 alkyl) or a salt thereof with a compound of Formula HR, or (b) condensing a compound of Formula III with a compound Z=CH-R (in which Z is O or S) or with a reactive derivative thereof, or (c) nitrating a compound of Formula IV and, if desired, converting a compound I obtained into a pharmalogically acceptable acid addition salt. The compounds I in which R is acylamino or cycloalkylamino can also be prepared by reacting a compound I in which R is NH 2 with an acylating or cycloalkylating agent. Starting materials of Formula II are prepared by reacting a compound III with appropriate ortho esters, or by reacting corresponding N- (C 1-6 acyl) derivatives of compounds III with trialkoxonium fluoborates. 3 - (5 - Nitro - 2 - furyl) - 5 - amino - 1,2,4- thiadiazole is prepared by reacting 5-nitro-2- furamidine hydrochloride with trichloromethylsulphenyl chloride to give 3-(5-nitro-2-furyl)-5- chloro-1,2,4-thiadiazole and reacting this with ammonia. 3 - (5 - Nitro - 2 - -furyl) - 6 - (aminomethyleneamino) - s - triazolo[4,3-b] - pyridazine is prepared by reacting 3-(5-nitro-2-furyl)-6-ethoxymethyleneamino - s - triazolo[4,3-b] - pyridazine with ammonia. 3 - (5 - Nitro - 2 - thienyl) - 6 - amino - striazolo[4,3-b]-pyridazine is prepared by reacting 5 - nitrothiophene - 2 - aldehyde with 3- hydrazino - 6 - chloropyridazine to give the corresponding hydrazone, cyclizing this to give 3 - (5 - nitro - 2 - thienyl) - 6 - chloro - s - triazolo- [4,3-b]pyridazine and aminating this by treating with potassium phthalimide followed by acidic fission to give the desired compound. Pharmaceutical compositions having antimicrobial activity, for oral or parenteral administration, comprise a compound I, or a pharmalogically acceptable acid addition salt thereof, together with a pharmaceutical carrier.