Antimicrobial and antifungal indolizino-isoquinoline cpds. - with (10)-nitro and (7)-oxo substits., useful as local antiseptics

摘要

Indolizino-isoquinolines of formula (I) and their acid addn., metal, and N-base addn. salts are new. In (I) R1 = H and R2 = H, amino or alkyl, opt. branched and opt. substd. on the final C by vinyl, ethynyl, COOH alkoxycarbonyl, CN, dialkoxymethyl, hydroxymethyl, dialkylaminoethyl (the 2 alkyls may complete an opt. N-methylated 5-6 membered satd. heterocycle opt. contg. an additional N, O or S atom) or trialkylammoniomethyl; or R2 is linear alkyl substd. on the final C by aminomethyl. In these cases R3+R4 form a bond. Alternatively, R1 + R4 = bond and R3 + R2 = CH2.CH(OR5)-. R5O=alkoxy substd. on the C atm alpha to R3-substd. N; all alkyl gps. and fragments contain 1-4C. (I) are antimicrobials and antifungals useful as local antiseptics. They are exceptionally low toxicity e.g. acute oral toxicity in mice is >0.75 g/kg. In an example 4-(2-hydroxyethylamino)-10-nitro-7-oxo-7H-indolizino 7,6,5-de isoquinoline was prepd. by reacting the corresp. 4-ethoxy cpd. with ethanolamine.