Design, Synthesis, and In Vitro Mitotic Evaluation of 3‐Amino‐Isoquinolinones as Anticancer Agents

Abstract

AbstractIn this study, a series of N‐(3‐amino‐1‐oxo‐2(1H)‐isoquinolinyl)benzamides and butyramides were designed and synthesized, and several of them showed mitotic therapeutic activity against renal and breast tumors. The most effective compounds were N‐(3‐amino‐1‐oxo‐2(1H)‐isoquinolinyl)benzamides bearing an electron‐withdrawing group on their benzamide moieties. N,N‐Carbonyldiimidazole promotes cross‐coupling between 2‐(cyanomethyl)benzoic acids and commercial acyl hydrazides, followed by intramolecular cyclization to afford these compounds via a two‐stage protocol. This process is enhanced through addition of imidazole ⋅ HCl which serves as a catalyst for the production of the acyl imidazole/imidazolium intermediate through the first stage. Gentle overnight heating at 60 °C after the addition of the acyl hydrazide during the second stage affords a final product that either precipitates from the solution or forms as a pure compound upon addition of a small amount of water.