56514-73-9Relevant academic research and scientific papers
Camptothecin analogs with bulky, hydrophobic substituents at the 7-position via a Grignard reaction
Manikumar, Govindarajan,Wadkins, Randy M.,Bearss, David,Von Hoff, Daniel D.,Wani, Mansukhlal C.,Wall, Monroe E.
, p. 5377 - 5381 (2004)
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.
