Wang Haixia, Ruan Zheming, Li James J, Simpkins Ligaya M, Smirk Rebecca A, Wu Shung C, Hutchins Robert D, Nirschl David S, Van Kirk Katy, Cooper Christopher B, Sutton James C, Ma Zhengping, Golla Rajasree, Seethala Ramakrishna, Salyan Mary Ellen K, Nayeem Akbar, Krystek Stanley R, Sheriff Steven, Camac Daniel M, Morin Paul E, Carpenter Brian, Robl Jeffrey A, Zahler Robert, Gordon David A, Hamann Lawrence G
Bristol-Myers Squibb Research and Development, PO Box 5400, Princeton, NJ 08543-5400, USA.
Bioorg Med Chem Lett. 2008 Jun 1;18(11):3168-72. doi: 10.1016/j.bmcl.2008.04.069. Epub 2008 May 1.
Several series of pyridine amides were identified as selective and potent 11beta-HSD1 inhibitors. The most potent inhibitors feature 2,6- or 3,5-disubstitution on the pyridine core. Various linkers (CH(2)SO(2), CH(2)S, CH(2)O, S, O, N, bond) between the distal aryl and central pyridyl groups are tolerated, and lipophilic amide groups are generally favored. On the distal aryl group, a number of substitutions are well tolerated. A crystal structure was obtained for a complex between 11beta-HSD1 and the most potent inhibitor in this series.
几系列吡啶酰胺被鉴定为选择性强效11β-羟基类固醇脱氢酶1（11β-HSD1）抑制剂。最有效的抑制剂在吡啶核心上具有2,6-或3,5-二取代。远端芳基和中心吡啶基之间的各种连接基（CH(2)SO(2)、CH(2)S、CH(2)O、S、O、N、键）均可耐受，且通常倾向于亲脂性酰胺基团。在远端芳基上，许多取代基也能很好地耐受。获得了11β-HSD1与该系列中最有效抑制剂之间复合物的晶体结构。
