“This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to understand the basis of pain and enhance clinical pain management.” In performance of work under this Task Order, the Contractor shall provide a full service facility and staff who shall support a medicinal chemistry discovery program beginning at the Hit-toLead (HTL) 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 Lu (Texas A&M University) in developing a novel therapeutic effective in treating pain by targeting the CB1 receptor allosterically. 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 treating post-seizure cognitive deficits. 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 the Lead Optimization phase. Additionally, the data generated from this task order 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 task order will be the basis to advance preclinical candidate compounds for further development i.e., advanced PK and toxicological evaluation in preparation of IND filings.