Diabetes mellitus retinopathy from

The title compound 1 (Fig. 1) is one of the two key intermediates used by Eli Lilly Co. in the synthesis of 2 (LY 333531), a protein kinase C inhibitor [1]. Compound 2 is in clinical trials for the treatment of retinopathy and nephropathy in patients with diabetes mellitus. A recent paper from Lilly describes [2] the development of a process to prepare 1 and 2 in multi-kilogram quantities. In this process, an acyclic bis-indolylmaleimide is reacted with 1, and the product obtained is converted into 2 in several steps as shown in Fig. 1. 

Diabetes mellitus is a group of metabolic diseases characterized by an increased blood glucose level secondary to defects in insulin secretion and/or action. According to the American Diabetes Association, as of 2002, the United States diabetes prevalence is 18.2 million people (6.3% of the population). Diabetics suffer from acute complications of the disease such as diabetic ketoacidosis and hyperosmolar nonketotic syndrome as well as chronic complications ranging from microvascular disease (nephropathy, neuropathy, retinopathy) to macrovascular disease (1). 

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