Saito Keiji, Shinozuka Tsuyoshi, Nakao Akira, Kiho Toshihiro, Kunikata Tomonori, Shiiki Takeshi, Nagai Yoko, Naito Satoru
Venture Science Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
End-Organ Disease Laboratories, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
Bioorg Med Chem Lett. 2019 Jul 15;29(14):1769-1773. doi: 10.1016/j.bmcl.2019.05.014. Epub 2019 May 9.
The synthesis and structure-activity relationships of a novel series of 3-aminothieno[2,3-b]pyridine-2-carboxamides were explored. Our efforts were focused on modifying the C-4 substituent of the thienopyridine ring to develop orally available bone anabolic agents. 4-Alkoxy derivatives were found to be novel ALPase enhancers without inhibitory effect on P450 activity. Among these derivatives, compound 6k was orally administered to ovariectomized rats, and it was found to significantly improve areal bone mineral density at a dose of 30 mg/kg/day.
探索了一系列新型3-氨基噻吩并[2,3-b]吡啶-2-甲酰胺的合成及其构效关系。我们致力于修饰噻吩并吡啶环的C-4取代基，以开发口服有效的骨合成代谢药物。发现4-烷氧基衍生物是新型碱性磷酸酶增强剂，对P450活性无抑制作用。在这些衍生物中，化合物6k经口服给予去卵巢大鼠，结果发现，在剂量为30 mg/kg/天时，它能显著提高骨面积密度。
