26-hydroxycholesterol--therapy for Ctx and Restenosis

Period of Performance: 02/08/1995 - 07/31/1995

Unknown

Phase 1 SBIR

Recipient Firm

Albany Molecular Research, Inc.
21 CORPORATE CIRCLE
Albany, NY 12203
Principal Investigator

Abstract

DESCRIPTION: 26-Hydroxycholesterol is a naturally occurring metabolic product derived from cholesterol. Recent investigations suggest that this metabolite plays a role as a feedback inhibitor of cholesterol synthesis and may be involved in down regulation of LDL receptors. The absence of 26-hydroxycholesterol has been postulated to be the molecular basis of the genetic disease cerebrotendinous xanthomatosis. The discovery that this compound is produced in vascular epithelium suggests that 26-hydroxycholesterol may have use for the prevention of restenosis following balloon angioplasty. 26-Hydroxycholesterol prepared by current procedures may be contaminated with significant quantities of diastereomeric impurities. Furthermore, engineering difficulties make the scale up of current syntheses unlikely. Both factors are obstacles in developing this potential drug. In order to develop this compound as a therapeutic agent, additional chemistry and biological efforts are required. In Phase I of this proposal, the development of a synthesis which provides the natural product with purity suitable for pharmaceutical development is proposed. This chemistry will also be used to prepare the unnatural diastereomer. HPLC studies will be conducted to develop a method for the determination of pharmaceutical grade purity. These efforts will set the stage for advanced biological testing and chemical development targeted for Phase II.