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

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

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

Bioorg Med Chem Lett. 2004 Nov 1;14(21):5377-81.

PubMed ID
15454230 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CamptothecinDNA topoisomerase 1EC 50 (nM)350N/AN/ADetails