Lee K, Hwang S Y, Hong S, Hong C Y, Lee C S, Shin Y, Kim S, Yun M, Yoo Y J, Kang M, Oh Y S
Biotech Research Insitute, LG Chemical Ltd., Taejon, Korea.
Bioorg Med Chem. 1998 Jun;6(6):869-76. doi: 10.1016/s0968-0896(98)00044-3.
An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (Ki = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (Ki = 0.045 nM).
一种脒基苯丙氨酸衍生物LB30057（2）被鉴定为一种强效（Ki = 0.38 nM）、选择性且口服活性的凝血酶抑制剂。作为对基于苯甲脒的凝血酶抑制剂研究的延续，我们通过用多种疏水基团取代萘基对化合物2进行了结构修饰。这项研究导致发现了几种在抑制凝血酶方面效力显著增强且不牺牲对胰蛋白酶的选择性和口服吸收的化合物。化合物23（Ki = 0.045 nM）具有最高活性。
