申请人:Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai
公开号:US04568490A1
公开(公告)日:1986-02-04
An aminopropylaminobleomycin represented by the following formula or a salt thereof, which is minimized in side effects such as pulmonary toxicity: [BX]--NH--(CH.sub.2).sub.3 --A--)CH.sub.2).sub.3 --B wherein [BX] represents the acyl group of bleomycinic acid whose formula differs from that of bleomycin acid by the removal of the hydroxyl group from the carboxyl group of said acid; A represents a group of the general formula ##STR1## wherein R.sub.1 is a lower alkyl or benzyl, R.sub.2 is a lower alkyl or benzyl, R is a lower alkylene, and n is 0 or 1; and B represents a group of the formula ##STR2## wherein (i) R.sub.3 is hydrogen and R.sub.4 is (a) benzyl substituted by one or more halogen atoms, provided that the benzyl is substituted by two halogen atoms when R.sub.1 is lower alkyl, (b) benzyl substituted by cyano, two or more alkoxy groups or two or more benzyloxy groups, (c) lower alkyl substituted by cycloalkyl or anthranyl, (d) phenylethyl substituted by one or more halogen atoms, or (e) diphenylethyl; or (ii) both R.sub.3 and R.sub.4 are benzyl which may be substituted by one or more (a) benzyloxy groups, (b) ring substituted benzyloxy groups in which the ring substituents may be one or more halogen atoms, lower alkoxy groups or benzyloxy groups, or (c) cycloalkylmethoxy groups; and a process for the preparation thereof.
下列式子或其盐所代表的氨丙基氨基双巯菌素,其副作用如肺毒性被减少:[BX]--NH--(CH.sub.2).sub.3 --A--)CH.sub.2).sub.3 --B,其中[BX]代表氨基甲酰基双巯菌素酸,其化学式与双巯菌素酸的化学式不同,因为其羧基中的羟基被去除;A代表下列通式的基团##STR1## 其中R.sub.1是较低的烷基或苄基,R.sub.2是较低的烷基或苄基,R是较低的亚烷基,n为0或1;B代表下列式子的基团##STR2## 其中(i)R.sub.3是氢,R.sub.4是(a)被一个或多个卤素原子取代的苄基,但当R.sub.1是较低的烷基时,苄基被两个卤素原子取代,(b)被氰基、两个或多个烷氧基或两个或多个苄氧基取代的苄基,(c)被环烷基或蒽基取代的较低的烷基,(d)被一个或多个卤素原子取代的苯乙基,或(e)二苯乙基;或(ii)R.sub.3和R.sub.4都是苄基,可以被一个或多个(a)苄氧基、(b)环取代的苄氧基取代,其中环取代基团可以是一个或多个卤素原子、较低的烷氧基或苄氧基,或(c)环烷基甲氧基取代;以及其制备方法。