Penning Thomas D, Chandrakumar Nizal S, Desai Bipin N, Djuric Stevan W, Gasiecki Alan F, Liang Chi-Dean, Miyashiro Julie M, Russell Mark A, Askonas Leslie J, Gierse James K, Harding Elizabeth I, Highkin Maureen K, Kachur James F, Kim Suzanne H, Villani-Price Doreen, Pyla E Yvonne, Ghoreishi-Haack Nayereh S, Smith Walter G
Department of Medicinal Chemistry, Pharmacia Corporation, Skokie, IL 60077, USA.
Bioorg Med Chem Lett. 2002 Dec 2;12(23):3383-6. doi: 10.1016/s0960-894x(02)00760-6.
The synthesis and biological evaluation of a series of functionalized pyrrolidine- and piperidine-containing analogues of our lead LTA(4) hydrolase inhibitor, SC-57461A, is described. A number of compounds showed excellent potency in our in vitro screens and several demonstrated good oral activity in a mouse ex vivo assay. These efforts led to the identification of SC-56938 (14) as a potent, orally active inhibitor of LTA(4) hydrolase.
本文描述了一系列含功能化吡咯烷和哌啶的类似物的合成及生物学评价，这些类似物是我们的先导白三烯A4水解酶抑制剂SC - 57461A的衍生物。许多化合物在我们的体外筛选中显示出优异的活性，并且有几种在小鼠离体试验中表现出良好的口服活性。这些研究工作使得SC - 56938（14）被鉴定为一种强效的、口服活性的白三烯A4水解酶抑制剂。
