Camptothecin analogs with bulky, hydrophobic substituents at the 7-position via a Grignard reaction.

Camptothecin analogs with bulky, hydrophobic substituents at the 7-position via a Grignard reaction.
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通过格氏反应在 7 位具有庞大的疏水取代基的喜树碱类似物。

DOI:
10.1016/j.bmcl.2004.08.010
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发表时间:
2004
期刊:
Bioorganic & medicinal chemistry letters.
影响因子:
--
通讯作者:
Wall,MonroeE
Wall,MonroeE
中科院分区:
--
文献类型:
--
作者:
Manikumar,Govindarajan;Wadkins,RandyM;Bearss,David;VonHoff,DanielD;Wani,MansukhlalC;Wall,MonroeE

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By developing a new synthetic procedure for introduction of side chains onto the camptothecin ring system, we were able to achieve the preparation of a number of analogs bearing bulky, hydrophobic groups directly attached to the 7-position. These include 7-tert-butylcamptothecin, 7-benzylcamptothecin and the corresponding 10,11-methylenedioxycamptothecins. This method involves the reaction of an appropriate orthoaminobenzonitrile with various Grignard reagents to give the corresponding orthoaminoketones. Friedlander condensation of the latter with the key tricyclic ketone leads to 7-substituted camptothecin analogs. We report the activity of these compounds as topoisomerase I poisons and their ability to inhibit growth of selected tumor cell lines.
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