凝血酶和Xa因子的选择性及双重作用口服活性抑制剂。
Selective and dual action orally active inhibitors of thrombin and factor Xa.
作者信息
Young Robert J, Brown David, Burns-Kurtis Cynthia L, Chan Chuen, Convery Máire A, Hubbard Julia A, Kelly Henry A, Pateman Anthony J, Patikis Angela, Senger Stefan, Shah Gita P, Toomey John R, Watson Nigel S, Zhou Ping
机构信息
GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK.
出版信息
Bioorg Med Chem Lett. 2007 May 15;17(10):2927-30. doi: 10.1016/j.bmcl.2007.03.080. Epub 2007 Mar 30.
The synthetic entry to new classes of dual fXa/thrombin and selective thrombin inhibitors with significant oral bioavailability is described. This was achieved through minor modifications to the sulfonamide group in our potent and selective fXa inhibitor (E)-2-(5-chlorothien-2-yl)-N-{(3S)-1-[(1S)-1-methyl-2-(morpholin-4-yl)-2-oxoethyl]-2-oxopyrrolidin-3-yl}ethenesulfonamide and these observed activity changes have been rationalised using structural studies.
本文描述了具有显著口服生物利用度的新型双靶点（因子Xa/凝血酶）抑制剂和选择性凝血酶抑制剂的合成方法。这是通过对我们强效且选择性的因子Xa抑制剂（E）-2-（5-氯噻吩-2-基）-N-{（3S）-1-[(1S)-1-甲基-2-(吗啉-4-基)-2-氧代乙基]-2-氧代吡咯烷-3-基}乙烯磺酰胺的磺酰胺基团进行微小修饰实现的，并且利用结构研究对观察到的活性变化进行了合理的解释。
Zotero 插件