Glucokinase Activator

Abstract

This chapter will detail early process development and a kilogram delivery of a Merck glucokinase activator 1 , shown in Figure 8.1 . Glucokinase, an enzyme that catalyzes phosphorylation of D -glucose, is a target for the treatment of type 2 diabetes. Glucokinase controls the conversion of glucose to glycogen and regulates glucose production in the liver. The expression of glucokinase is controlled by insulin in the liver and D -glucose in the pancreatic β -cells [1] .The key synthetic challenges in the target molecule 1 were the chiral 2 -arylpyrrolidine fragment, the densely functionalized benzimidazole ring, and the hindered biaryl ether linkage.