Serenix Pharmaceuticals LLC (SRX) will develop drugs for stress-related affective disorders and depression. Serenix acquired a series of vasopressin receptor antagonists from Eli Lilly Company and refined these molecules through manipulations of various structural zones. A subset of these molecules exhibited reasonable affinity for the vasopressin receptor subtype involved in depression. With Phase I support, this series was chemically modified and a candidate that exhibits good binding affinity and blocks biological effects at the target human receptor was identified. The overall goal of Phase II research is to identify additional candidates based on chemical and both in vitro and in vivo biological activity in order to progress toward the filing of Investigational New Drug (IND) applications for two promising candidates. To reach this goal, SRX will pursue the following objectives i) continue classic and combinatorial chemistry based on Phase I findings to produce additional candidate molecules, ii) screen these for target receptor affinity, focus on those with Kds < 10 nM, and test the high affinity compounds for in vitro and in vivo biological activity, and iii) use CROs to conduct tests for oral absorption, bioavailability, metabolism, mutagenicity, and toxicity. The completion of the proposed research will provide data that validates novel drug candidates and meets a portion of the chemical and biological criteria established by the FDA for IND applications.