Advancements in the manufacturing routes for the synthesis of marketed PARP inhibitors

Abstract

The significant role of PARP inhibitors in the treatment of various cancers, especially ovarian and breast cancer, is very well established. To date, seven PARP inhibitors have received marketing approval, namely, olaparib, rucaparib, niraparib, talazoparib, fuzuloparib, pamiparib and senaparib, in various countries. This article reviews the manufacturing routes for the synthesis of these marketed drugs reported in the literature since 2017. Over the past decade, synthetic strategies for PARP inhibitors have transitioned from step-intensive medicinal chemistry synthesis routes to more streamlined, industrially viable processes. These modern approaches integrate key transformations, such as amide bond formation, C–H activation, carbopalladation, heterocycle construction, and stereocontrolled cyclisation, enabling improved efficiency and scalability. In parallel, the incorporation of green chemistry principles, particularly in one of the manufacturing routes of olaparib, has led to more sustainable process development.