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 Lettjournal_title
Bioorganic & medicinal chemistry lettersauthors
Manikumar G,Wadkins RM,Bearss D,Von Hoff DD,Wani MC,Wall MEdoi
10.1016/j.bmcl.2004.08.010subject
Has Abstractpub_date
2004-11-01 00:00:00pages
5377-81issue
21eissn
0960-894Xissn
1464-3405pii
S0960-894X(04)01018-2journal_volume
14pub_type
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