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

Abstract:

: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.

journal_name

Bioorg Med Chem Lett

authors

Manikumar G,Wadkins RM,Bearss D,Von Hoff DD,Wani MC,Wall ME

doi

10.1016/j.bmcl.2004.08.010

subject

Has Abstract

pub_date

2004-11-01 00:00:00

pages

5377-81

issue

21

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(04)01018-2

journal_volume

14

pub_type

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