Lee Koo, Jung Won-Hyuk, Park Cheol Won, Park Hee Dong, Lee Sun Hwa, Kwon O Hwan
Life Science R&D, LGCI, PO Box 61 Yu-Sung, Science Town, Taejon 305-380, Republic of
Bioorg Med Chem Lett. 2002 Apr 8;12(7):1017-22. doi: 10.1016/s0960-894x(02)00093-8.
A series of noncovalent tripeptidic thrombin inhibitors incorporating amidrazone, amine and amidine functions at P1 was investigated. While the amidrazone and the amine series displayed limited oral absorption, the amidine series demonstrated generally good oral absorption and strong antithrombotic activity; the single-digit picomolar K(i) achieved from this series is among the best yet reported. The present work highlights the benzamidine compound 11f (LB30812) that exhibits excellent overall profiles of potency, oral absorption and antithrombotic efficacy.
研究了一系列在P1位含有脒腙、胺和脒功能的非共价三肽凝血酶抑制剂。虽然脒腙系列和胺系列显示出有限的口服吸收，但脒系列总体上表现出良好的口服吸收和较强的抗血栓活性；该系列实现的个位数皮摩尔K(i)是迄今报道的最佳结果之一。目前的工作突出了苯甲脒化合物11f（LB30812），它在效力、口服吸收和抗血栓疗效方面表现出优异的综合特性。
