This SBIR grant is sought for the purpose of commercializing a promising and needed drug NIH 10497(D-1). It is a novel, orally active opioid with a unique chiral N-substituent that confers an unprecedented activity profile. It has promise as a safe potent analgesic and as a treatment for addiction, not with maintenance, but with potential for cure. NIH 10497 has already been shown by NIDA funded studies to possess an unusual balance of agonist activities at the kappa, mu, and delta opioid receptors. In particular, the drug was discovered to substitute for Morphine in dependent animals, while causing no physical dependence in non-dependent animals. This suggests a novel profile of activities. NIH 10497 was originally discovered in 1980 but was never marketed. The inventor of NIH 10497 founded a small business, Phoenix PharmaLabs, for the purpose of commercializing this drug. Our first goal is to create fresh Patents (the original Patents have expired) for a new Use and, with SBIR support, for a critical new Method of large-scale synthesis that is stereoselective and scalable. This will require the discovery of an improved reductive amination step using a chiral reducing agent. NIH 10497 also lacks sufficient in vivo evaluation, so under this grant, a consortium agreement with Dr. Lou Harris will fund a Morphine Substitution Study (MSS) in the rat at VCU. The PI and two of the consultants, Dr. Toll and Dr. Lukeman have traveled to China three times to meet with Ms. Peng Yan and interested investors. Investors are attracted to NIH 10497 for a number of reasons. Toxicology and Clinic trials are much less expensive in China and there is strong need for a treatment of addiction in that country. The PI and Dr. DeGraw will develop new synthetic methods for NIH 10497 to achieve a Method Patent that is crucial to attract the Investor. Dr. Harris will supervise the MS study in rats, and Dr. Lukeman will assist in the pharmacologic assessment of the results and determine the valuation of NIH 10497 in preparation for commercialization.
Thesaurus Terms: analgesic, drug design /synthesis /production, method development, opiate alkaloid, opioid receptor drug abuse chemotherapy, stimulant /agonist
