Laboratory for Medicinal Chemistry Research, Shionogi & Co., Ltd., 1-1 Futaba-cho 3-chome, Toyonaka, Osaka 561-0825, Japan.
Office for Children's Bright Future, Shionogi & Co., Ltd., 2F, Nissay Yodoyabashi East, 3-13, Imabashi 3-chome, Chuo-ku, Osaka 541-0042, Japan.
Bioorg Med Chem Lett. 2020 Dec 15;30(24):127636. doi: 10.1016/j.bmcl.2020.127636. Epub 2020 Oct 22.
The P2X3 receptor is an attractive target for the treatment of pain and chronic coughing, and thus P2X3 antagonists have been developed as new therapeutic drugs. We previously reported selective P2X3 receptor antagonists by derivatization of hit compound 1. As a result, we identified hit compound 3, the structure of which was similar to hit compound 1. On the basis of SAR studies of hit compound 1, we modified hit compound 3 and compound 42 was identified as having analgesic efficacy by oral administration.
P2X3 受体是治疗疼痛和慢性咳嗽的有吸引力的靶点，因此已将 P2X3 拮抗剂开发为新型治疗药物。我们之前通过对命中化合物 1 进行衍生化来报道选择性 P2X3 受体拮抗剂。结果，我们鉴定了命中化合物 3，其结构与命中化合物 1 相似。基于对命中化合物 1 的 SAR 研究，我们对命中化合物 3 进行了修饰，鉴定出化合物 42 具有口服镇痛作用。
