A Comprehensive Literature Review on Efficient Synthetic Approaches and Polymorphism of Pazopanib (Votrient), a Tyrosine Kinase Inhibitor

Abstract

Angiogenesis involves the development of new blood vessels from the pre-existing vasculature. In cancer, an inappropriate or pathological angiogenesis reinforces tumor growth by feeding with nutrient and oxygen. Central to the process of angiogenesis is vascular endothelial growth factor (VEGF) and its receptor (VEGFR), as they regulate angiogenesis and vascular permeability. To stop tumor angiogenesis by cutting off the blood supply, a multitude of angiogenesis inhibitors (antiangiogenic agents or anticancer drugs) have been developed. In pursuit of developing an effective angiogenesis inhibitor, a novel pyrimidine derivative, an inhibitor of VEGFR-2 kinase activity later known as “VOTRIENT (Pazopanib)” was developed by GlaxoSmithKline and approved by the FDA in October 2009 for treatment of advanced renal cell cancer. Later, it was also approved by the FDA for the treatment of advanced soft tissue sarcoma in April 2012. In the literature, there are multiple synthetic pathways reported and the present work reviews the literature related to the synthesis of Pazopanib emphasizing applicability at a commercial scale. The main purpose of this review paper is to provide a comprehensive overview of different existing routes of synthesis with relevant comparison, reported polymorphs, and suggesting further development.