A New Drug for Depression

描述(由申请人提供)： 长期目标：Serenix制药公司(SP)将为 中枢神经系统疾病的治疗。 策略：SP从ELI获得一系列加压素受体拮抗剂 礼来公司，并通过操纵这些分子 各种构造区。这些拮抗剂的一个子集(铅系列)展示 参与抑郁症的加压素受体亚型的合理亲和力 以及与压力相关的情感障碍。销售线索系列需要改进以 优化亲和力(小于5.0 NM)并进行早期测试以演示 生物活性。平台分子有四个基本的结构区； 其中两个将是拟议研究的重点。第一阶段的目标是 (一)利用经典和组合化学对结构带进行修饰 产生约200个化合物先导系列，(Ii)筛选这些化合物作为靶标 受体亲和力和专注于KDS<5 NM的患者，以及(Iii)测试 具有体外生物活性的高亲和力化合物。研究结果显示， 结合与亲和力、结构多样性、 结构吸引力和QSAR模型将确定有前景的化合物 用于第二阶段的口服吸收、稳定性、新陈代谢、毒性测试， 和药效。 拟议的商业应用：SP将专注于开发一种治疗抑郁症和应激相关情感障碍的新药。1999年，NIMH报告称，美国有超过1900万成年人患有抑郁症，使其成为最常见的严重中枢神经系统疾病。建议的药物代表了一种新的药理学方法，不同于目前用于这些疾病的三环类药物、SSRIs和NRIs。因此，它可能会占据相当大的市场份额。

DESCRIPTION (provided by applicant): Long Term Goals: Serenix Pharmaceuticals (SP) will develop drugs for the treatment of CNS disorders. Strategy: SP acquired a series of vasopressin receptor antagonists from Eli Lilly and Company and has refined these molecules through manipulations of various structural zones. A subset of these antagonists (LEAD SERIES) exhibit reasonable affinity for the vasopressin receptor subtype involved in depression and stress-related affective disorders. The LEAD SERIES requires refinement to optimize affinity (less than 5 .0 nM) and early stage testing to demonstrate biological activity. The platform molecule has four essential structural zones; two of these will be the focus of the proposed research. Phase I objectives are (i) utilize classical and combinatorial chemistry to modify structural zones on the LEAD SERIES to generate ca. 200 compounds, (ii) screen these for target receptor affinity and focus on those with Kds less than 5 nM, and (iii) test the high affinity compounds for in vitro biological activity. The findings, combined with considerations related to affinity, structural diversity, structural attractiveness, and QSAR models, will identify promising compounds for testing in Phase II for oral absorption, stability, metabolism, toxicity, and efficacy. PROPOSED COMMERCIAL APPLICATION: SP will focus on the development of a novel drug for the treatment of depression and stress-related affective disorders. In 1999, the NIMH reported that depression affects over 19,000,000 adults in the United States, making it the most common serious CNS disease. The proposed drug represents a novel pharmacological approach that differs from the tricyclics, SSRIs, and NRIs currently used for these disorders. It therefore may capture significant market share.