Functionalized Organozinc Reagents in Medicinal Chemistry: Discovery of Novel Drug Candidates

Discovery, optimization, and early development of drug candidates are very challenging and require a versatile synthetic chemistry toolbox. Organozinc chemistry is a powerful methodology for carbon–carbon bond formation which tolerates several functional groups that are critical for maintaining good physicochemical properties of drug molecules. Here we demonstrate that organozinc chemistry offers facile solutions to otherwise challenging medicinal chemistry problems commonly encountered during lead optimization. In this review, we summarize several examples in which utilization of organozinc-mediated couplings enabled us to rapidly explore a medicinal chemistry hypothesis using readily available intermediates. This chemistry allowed us to make rapid decisions with limited chemistry resources. 1 Introduction 2.1 Alpha4 Integrin Antagonists 2.2 CRTH2 Antagonists 2.3 Glucokinase (GK) Activators 2.4 Leukotriene B4 (LTB 4 ) Receptor Antagonists 2.5 Janus Activated Kinase 3 (JAK3) Inhibitors 2.6 Synthesis of Novel Scaffolds 3 Conclusions 4 Experimental Methods