DEOXYKANAMYCIN B DERIVATIVES

摘要

1505852 Tobramycin and 31,41-dideoxykanamycin B derivatives PFIZER Ltd 22 Oct 1976 [25 Oct 1975] 43950/75 Heading C2C Novel tobramycin and 31,41-dideoxykanamycin B derivatives of the general Formula I wherein R1 and R2 are each a hydrogen atom or C 1-6 alkyl group, R3 and R4 are each a hydrogen atom or hydroxyl group and n is 1-4, and pharmaceutically acceptable acid addition salts thereof are prepared (a) by reacting tobramycin, 31,41-dideoxykanamycin B or a protected amino derivative of the general Formula II wherein R5 is a monovalent protecting group for a primary amino group, with an aldehyde of the general formula wherein R6 and R7 are each a C 1-6 alkyl group or R6 is a protecting group for a primary or secondary amino group and R7 is a hydrogen atom or C 1-6 alkyl group, and simultaneously or subsequently reducing the Schiffs base so formed to the corresponding secondary amine and then, if necessary, removing the protecting groups R6 and/or R6, (b) by reacting tobramycin or 31,41-dideoxykanamycin B with an acylating agent of the general formula wherein R6 is a protecting group for a primary or secondary amino group, R7 is a hydrogen atom or C 1-6 alkyl group and X is a halogen atom of N-oxy-succinimide group, removing the protecting group and reducing the amide product; and (c) when R1, R2 and R3 are each hydrogen and n is 1, by reacting a compound II with acrylonitrile, removing the protecting group and reducing the 61-N-cyanoalkyl product; followed optionally by salification of the product. Pharmaceutical compositions having antibacterial activity comprise, as active ingredient, a tobramycin or 31,41-dideoxykanamycin B derivative (I) or pharmaceutically acceptable acid addition salt thereof, together with a pharmaceutically acceptable carrier.