Design, synthesis, and biological evaluation of indole-modified tamoxifen relatives as potent anticancer agents.

Modulation of existing drugs is an attractive strategy to achieve improved activity in cancer therapy by lowering their effective dose. Preparation of relatives has been suggested and explored to improve the therapeutic effect of anticancer agents. In the current study, we attempted to modulate tamoxifen (TMX) by replacing the -phenyl ring in its backbone with an indole or oxindole.

Access to C5-Alkylated Indolines/Indoles via Michael-Type Friedel-Crafts Alkylation Using Aryl-Nitroolefins.

A straightforward synthetic route toward C5-alkylated indolines/indoles has been developed. The strategy is composed of Zn(OTf)-catalyzed Friedel-Crafts alkylation of N-benzylindolines with nitroolefins, and a series of diverse indolines was first obtained in up to 99% yield. This reaction provides a direct and practical route to a variety of the C5-alkylated indolines which were also utilized for accessing corresponding indoles.