The National Institute on Neurological Disorders and Stroke (NINDS) and the NIH Blueprint Neurotherapeutics Network (BPN) http://neuroscienceblueprint.nih.gov/bpdrugs/index.htm have a need for the Medicinal Chemistry Support Program (MCSP) to provide a full-service facility and staff who would support a medicinal chemistry discovery program beginning at the Exploratory Chemistry phase to develop structure activity relationship (SAR) analysis and design, synthesis, in vitro absorption, distribution, metabolism, excretion and toxicology (ADMET), computational chemistry/Computer Aided Drug Discovery (CADD) and compound logistics of storage and shipping to support the Contributor Mouradian/Disney (Rutgers/Scripps) to develop a novel therapeutic effective in Parkinson’s. This will be achieved by advancing the SAR/SPR of their small molecule heterocyclic starting compound utilizing their assays and in vitro ADMET to identify novel, selective inhibitors of the target enzyme that are directed at Parkinson’s. Our drug discovery approach will be to synthesize novel ligands based on the heterocyclic scaffold that are potent inhibitors. Candidate molecules will undergo profiling to assess criteria specifically related to the physicochemical properties of compounds in a therapeutic setting, including enzyme selectivity and tests to determine potential interactions with key metabolic enzyme systems. The goal is to advance the project to go/no go decisions and to progress to each of the Option phases in succession (start of Hit-to-Lead and start of Lead Optimization). The data generated from this contract will be used by NINDS, contributors or sponsored investigators in support of Investigational New Drug (IND) application directed preclinical activities. The results of the efforts of this contract will be the basis to advance preclinical candidate compounds for further development i.e., advanced PK and toxicological evaluation in preparation of IND filings. The ultimate goal of the NIH programs served by this contract and of individual projects is to bring new drugs to market. To this end, the NIH has been granted a Determination of Exceptional Circumstances (DEC) to incorporate the Department of Health and Human Services Acquisition Regulation (HHSAR) clauses at 352.227-11, Patent-Rights-Exceptional Circumstances and 352.227-14, Rights in Data – Exceptional Circumstances, as part of any contract resulting from this solicitation. The HHSAR Clauses will enable the Contributors to retain control of the intellectual property for compounds created through the Medicinal Chemistry Support Program for Therapeutic Development (MCSP).