SBIR-STTR Award

The goal of this program is to develop a new process for rapidly generating mixtures of derivatives (i.e., derivative libraries) of compounds with pharmaceutical activity. Such derivatives are made from compounds possessing biological activity or from close analogues of these compounds, with the goal of identifying related compounds with more attractive pharmaceutical properties, such as aqueous solubility, GI-tract permeability, or target selectivity. The proposed process should make it possible to produce structurally distinct derivatives rapidly and to produce derivatives not readily accessible from the parent compound using traditional chemical methods. The process promises to greatly accelerate the optimization and development of pharmaceutical leads. In Phase I, it is planned to demonstrate the feasibility of this process by derivatizing known agonists of three nicotinic acetylcholine receptors - compounds that exhibit interesting neuroprotective activities but have not yet been developed into commercial pharmaceuticals. In Phase II, the process and reactor design would be optimized for rapidly generating derivative libraries from a range of starting materials using a series of derivatizing molecules. Due to the promise of this technology, a major pharmaceutical company has agreed to collaborate with Bend Research by screening the derivative libraries for bioactivity for a broad range of therapeutic uses.

Thesaurus Terms:
biomedical equipment development, bioreactor, chemical registry /resource, chemical synthesis method development, nicotine, nonclinical biomedical equipmentNational Institute of General Medical Sciences (NIGMS)

This goal of this program is to develop a new process for rapidly generating mixtures of derivatives (i.e., derivative libraries) with chemical structures that are based on the structure of a single bioactive parent compound. The proposed process makes it possible to produce structurally distinct derivatives rapidly and to produce derivatives not readily accessible from the parent compound using traditional chemical methods. The process promises to greatly accelerate the optimization and development of pharmaceutical leads. In Phase I, we demonstrated feasibility by producing chemical libraries that contained 50 or more derivative compounds based on two parent structures: caffeine and xanthine. The library reactions were reproducible, and specific compounds were produced in sufficient amounts to allow isolation, testing, and structural characterization. These libraries were shown to contain bioactive compounds and were suitable for use with high- throughput screening. Phase II work will focus on development of the process through extensive structural elucidation of new, more chemically diverse libraries. The effects of various derivatizing molecules and preparation variables will be examined. Bend Research plans to develop a business based on this technology that will produce custom libraries for pharmaceutical clients and provide further services of isolation and structural elucidation of promising compounds. PROPOSED COMMERCIAL APPLICATION This process would provide a new, inexpensive method for rapidly generating libraries of compounds that are closely related to pharmaceutically active parent compounds but that differ in a direct structural feature. Successful implementation could significantly reduce the time and effort required to generate pharmaceutically valuable derivatives from parent compounds. Due to its speed and potential for forming classes of derivatives not readily accessible by traditional chemical methods, this process has breakthrough potential for increasing the efficiency of drug discovery.

Thesaurus Terms:
bioreactor, chemical registry /resource, chemical synthesis, combinatorial chemistry, technology /technique development chemical structure high performance liquid chromatography, mass spectrometry