1,2,4-三唑并吡啶作为人1型11β-羟基类固醇脱氢酶（11β-HSD-1）抑制剂的优化
Optimization of 1,2,4-Triazolopyridines as Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1).
作者信息
Li Jun, Kennedy Lawrence J, Wang Haixia, Li James J, Walker Steven J, Hong Zhenqiu, O'Connor Stephen P, Nayeem Akbar, Camac Daniel M, Morin Paul E, Sheriff Steven, Wang Mengmeng, Harper Timothy, Golla Rajasree, Seethala Ramakrishna, Harrity Thomas, Ponticiello Randolph P, Morgan Nathan N, Taylor Joseph R, Zebo Rachel, Gordon David A, Robl Jeffrey A
机构信息
Department of Medicinal Chemistry, Department of Biology, Lead Evaluation, CADD, Department of Pharmaceutical Candidate Optimization, Bristol-Myers Squibb , Bldg 13, Princeton, New Jersey 08543-5400, United States.
Protein Science & Structure, Research & Development, Bristol-Myers Squibb , Princeton, New Jersey 08543, United States.
出版信息
ACS Med Chem Lett. 2014 May 22;5(7):803-8. doi: 10.1021/ml500144h. eCollection 2014 Jul 10.
Small alkyl groups and spirocyclic-aromatic rings directly attached to the left side and right side of the 1,2,4-triazolopyridines (TZP), respectively, were found to be potent and selective inhibitors of human 11β-hydroxysteroid dehydrogenase-type 1 (11β-HSD-1) enzyme. 3-(1-(4-Chlorophenyl)cyclopropyl)-8-cyclopropyl-[1,2,4]triazolo[4,3-a]pyridine (9f) was identified as a potent inhibitor of the 11β-HSD-1 enzyme with reduced Pregnane-X receptor (PXR) transactivation activity. The binding orientation of this TZP series was revealed by X-ray crystallography structure studies.
分别直接连接在1,2,4-三唑并吡啶（TZP）左侧和右侧的小烷基和螺环芳环，被发现是人类11β-羟基类固醇脱氢酶1型（11β-HSD-1）酶的强效和选择性抑制剂。3-(1-(4-氯苯基)环丙基)-8-环丙基-[1,2,4]三唑并[4,3-a]吡啶（9f）被鉴定为11β-HSD-1酶的强效抑制剂，其孕烷X受体（PXR）反式激活活性降低。通过X射线晶体学结构研究揭示了该TZP系列的结合取向。
Zotero 插件