他汀类衍生的1,3 - 恶嗪烷 - 2 - 酮作为LFA - 1/ICAM - 1相互作用的亚微摩尔抑制剂：代谢不稳定的香草基侧链的稳定化

Statin-derived 1,3-oxazinan-2-ones as submicromolar inhibitors of LFA-1/ICAM-1 interaction: stabilization of the metabolically labile vanillyl side chain.

作者信息

Ullrich Thomas, Baumann Karl, Welzenbach Karl, Schmutz Simone, Camenisch Gian, Meingassner Josef G, Weitz-Schmidt Gabriele

机构信息

Novartis Institutes for Biomedical Research, A-1235 Vienna, Austria.

出版信息

Bioorg Med Chem Lett. 2004 May 17;14(10):2483-7. doi: 10.1016/j.bmcl.2004.03.006.

DOI:10.1016/j.bmcl.2004.03.006

PMID:15109637

Abstract

Modification of the vanillyl substituent on a potent, semisynthetic lymphocyte function-associated antigen (LFA)-1/intercellular adhesion molecule (ICAM)-1 binding inhibitor of the statin family resulted in metabolically more stable analogues that displayed submicromolar inhibitory activity in vitro and considerable anti-inflammatory activity in vivo. The benzodioxole derivative 2b emerged with the best overall profile.

摘要

对他汀类强效半合成淋巴细胞功能相关抗原（LFA）-1/细胞间黏附分子（ICAM）-1结合抑制剂上的香草基取代基进行修饰，得到了代谢更稳定的类似物，这些类似物在体外表现出亚微摩尔级的抑制活性，在体内具有显著的抗炎活性。苯并二恶唑衍生物2b表现出最佳的综合性能。