新型甲状旁腺素受体 1 拮抗剂的发现：设计、合成及构效关系。
Discovery of novel PTHR1 antagonists: Design, synthesis, and structure activity relationships.
机构信息
Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Medicinal Chemistry Research Laboratories, Daiichi Sankyo Co, Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
出版信息
Bioorg Med Chem Lett. 2019 Sep 15;29(18):2613-2616. doi: 10.1016/j.bmcl.2019.07.052. Epub 2019 Jul 29.
The discovery and optimization of a novel series of PTHR1 antagonists are described. Starting from known PTHR1 antagonists, we identified more potent 1,4-benzodiazepin-2-one derivatives by means of a scaffold-hopping approach. The representative compound 23 (DS08210767) exhibited nanomolar-level PTHR1 antagonist activity and potential oral bioavailability in a pharmacokinetic study.
描述了一种新型甲状旁腺素受体 1（PTHR1）拮抗剂的发现和优化。我们从已知的 PTHR1 拮抗剂出发，通过支架跳跃方法确定了更有效的 1,4-苯并二氮杂卓-2-酮衍生物。代表性化合物 23（DS08210767）在药代动力学研究中表现出纳摩尔级别的 PTHR1 拮抗剂活性和潜在的口服生物利用度。
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