Ligand Pharmaceuticals, Inc., 3000 Eastpark Boulevard, Cranbury, NJ 08512, USA.
Bioorg Med Chem Lett. 2010 Sep 15;20(18):5394-7. doi: 10.1016/j.bmcl.2010.07.118. Epub 2010 Aug 1.
The discovery, synthesis, and preliminary structure-activity relationship (SAR) of a novel class of vasopressin V3 (V1b) receptor antagonists is described. Compound 1, identified by high throughput screening of a diverse, three million-member compound collection, prepared using ECLiPS technology, had good activity in a V3 binding assay (IC50=0.20 microM), but less than desirable physicochemical properties. Optimization of compound 1 yielded potent analogs 19 (IC50=0.31 microM) and 24 (IC50=0.12 microM) with improved drug-like characteristics.
本文描述了一种新型血管加压素 V3（V1b）受体拮抗剂的发现、合成和初步的结构-活性关系（SAR）。化合物 1 通过高通量筛选一个多样化的、三百万个成员的化合物库，使用 ECLiPS 技术制备，在 V3 结合测定中具有良好的活性（IC50=0.20 微摩尔），但理化性质不理想。对化合物 1 的优化得到了具有改善的类药性的有效类似物 19（IC50=0.31 微摩尔）和 24（IC50=0.12 微摩尔）。
