FOERFARANDE FOER FRAMSTAELLNING AV BRONKOLYTISKT AKTIVA TEOFYLLINDERIVAT

摘要

1350968 Basic theophylline derivatives DEUTSCHE GOLDUND SILBER-SCHEIDEANSTALT 27 July 1971 [27 July 1970] 35116/71 Heading C2C Novel compounds of the general Formula II in which R1 and R2, which are the same or different, and are C 1-4 alkyl and one of R1 and R2 can also be hydrogen, R3 is hydrogen, or C 1-4 alkyl and n is 1 or 2, optical and stereoisomers and salts thereof may be prepared by (a) reduction of the keto group of a compound III to a hydroxyl group; (b) condensing a compound IV and compound V wherein one of X and Z is halogen and the other is amino; (c) condensing theophylline or a metal salt thereof with a compound VI wherein Hal is a halogen atom; (d) reductive condensation of compound VII with VIII wherein one of V and W is -C(R4) = O and the other is -(R4)NH 2 where R4 is hydrogen or a C 1-4 alkyl and Y is oxygen, or a hydrogen and hydroxyl; (e) reaction of a compound IV in which Z is NH 2 or a protected amino group with a compound IX wherein in any reaction any of the amino and/or phenolic hydroxy groups may be protected during the reaction and either the protective group removed under the conditions of the reaction or subsequently removed. The compounds III may be prepared by a process similar to (b) above wherein Z in IV is benzylamino and in V a keto group replaces hydrogen and hydroxyl on the carbon atomαto the phenyl. 1 - (3,4 - Dibenzyloxyphenyl) - 1 - hydroxy - 2- bromoethane may be prepared by reduction of 1 - (3,4 - dibenzyloxyphenyl) - 1 - oxo - 2 - bromoethane. 7 - (2 - Methyl - 3 - aminopropyl) - theophylline may be prepared by reaction of 7-(2-methyl-3 chloropropyl)-theophylline and ammonia. p - Hydroxyphenylacefylcarbinol may be prepared by hydration of p-hydroxyphenylethynylcarbinol. Pharmaceutical compositions of compounds II show broncholytic activity without tachycardia when administered orally, parenterally or perlingually with the usual excipients.