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

Abstract In this study, a series of N ‐(3‐amino‐1‐oxo‐2(1 H )‐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(1 H )‐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.