新型 SIPI-7623 衍生物的合成及生物评价作为法尼醇 X 受体 (FXR) 拮抗剂。
Synthesis and biological evaluation of novel SIPI-7623 derivatives as farnesoid X receptor (FXR) antagonists.
机构信息
Department of Clinical Pharmacy, Taizhou Hospital of Zhejiang Province, Xi Men Street No. 150, Linhai, 317000, Zhejiang Province, China.
Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, 201203, China.
出版信息
Mol Divers. 2019 Feb;23(1):19-33. doi: 10.1007/s11030-018-9843-2. Epub 2018 Jul 4.
Most of reported steroidal FXR antagonists are restricted due to low potency. We described the design and synthesis of novel nonsteroidal scaffold SIPI-7623 derivatives as FXR antagonists. The most potent compound A-11 (IC = 7.8 ± 1.1 μM) showed better activity compared to SIPI-7623 (IC = 40.8 ± 1.7 μM) and guggulsterone (IC = 45.9 ± 1.1 μM). Docking of A-11 in FXR's ligand-binding domain was also studied.
大多数报道的甾体 FXR 拮抗剂由于效力低而受到限制。我们描述了新型非甾体支架 SIPI-7623 衍生物作为 FXR 拮抗剂的设计和合成。最有效的化合物 A-11（IC = 7.8 ± 1.1 μM）与 SIPI-7623（IC = 40.8 ± 1.7 μM）和古柯甾酮（IC = 45.9 ± 1.1 μM）相比显示出更好的活性。还研究了 A-11 在 FXR 配体结合域中的对接。
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