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    • 3. 发明授权
    • Camptothecin derivatives and process for preparing same
    • 喜树碱衍生物及其制备方法
    • US4604463A
    • 1986-08-05
    • US627980
    • 1984-07-05
    • Tadashi MiyasakaSeigo SawadaKenichiro NokataEiichi SuginoMasahiko Mutai
    • Tadashi MiyasakaSeigo SawadaKenichiro NokataEiichi SuginoMasahiko Mutai
    • A61K31/47A61K31/495A61K31/535A61P35/00C07D491/22
    • C07D491/22
    • New camptothecin derivatives possessing high anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R.sup.1 is a hydrogen atom, a halogen atom or an alkyl group with 1-4 carbon atoms and X is a chlorine atom or --NR.sup.2 R.sup.3 where R.sup.2 and R.sup.3 are the same or different and each represents a hydrogen atom, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted carbocyclic or heterocyclic group, with the proviso that when both R.sup.2 and R.sup.3 are the substituted or unsubstituted alkyl groups, they may be combined together with the nitrogen atom, to which they are bonded, to form a heterocyclic ring which may be interrupted with --O--, --S-- and/or >N--R.sup.4 in which R.sup.4 is a hydrogen atom, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted phenyl group and wherein the grouping --O--CO--X is bonded to a carbon atom located in any of the 9-, 10- and 11-positions in the ring A of camptothecin, as well as an ammonium salt or an alkali metal salt thereof. These new camptothecin derivatives are prepared by reacting a 7-R.sup.1 -camptothecin derivative having a hydroxyl group in any of the 9-, 10- and 11-positions on the ring A thereof with phosgen and then reacting, if necessary, the resultant 7-R.sup.1 -camptothecin derivative having a chlorocarbonyloxy group in the same position on the ring A thereof with an amine HNR.sup.2 R.sup.3 or by reacting a 7-R.sup.1 -camptothecin derivative having a hydroxyl group in any of the 9-, 10- and 11-positions on the ring A thereof with a carbamoyl chloride Cl-CONR.sup.2 R.sup.3.
    • 新的喜树碱衍生物具有高的抗肿瘤活性,具有轻微的毒性,由以下通式表示:其中R1是氢原子,卤素原子或具有1-4个碳原子的烷基,X是一个氯 原子或-NR 2 R 3,其中R 2和R 3相同或不同,并且各自表示氢原子,取代或未取代的具有1-4个碳原子的烷基或取代或未取代的碳环或杂环基团,条件是当R 2和 R3是取代或未取代的烷基,它们可以与它们所键合的氮原子结合在一起形成杂环,其可被-O - , - S-和/或> N-R 4中断 其中R4是氢原子,取代或未取代的具有1-4个碳原子的烷基或取代或未取代的苯基,并且其中-O-CO-X基团键合到位于9-, 十一和十一个位置在环A的 以及铵盐或其碱金属盐。 这些新的喜树碱衍生物通过使具有羟基的7-R1-喜树碱衍生物在其环A上的9-,10-和11-位中的光气与光气反应制备,然后如果需要,使所得的7- 在环A上具有与其相同位置上的氯羰基氧基的R1-喜树碱衍生物与胺HNR2R3反应,或通过使9-,10-和11-位任何一个具有羟基的7-R1-喜树碱衍生物在 环A与氨基甲酰氯Cl-CONR2R3反应。