Shuto Daisuke, Kasai Soko, Kimura Tooru, Liu Ping, Hidaka Koushi, Hamada Takashi, Shibakawa Saeko, Hayashi Yoshio, Hattori Chinatsu, Szabo Beata, Ishiura Shoichi, Kiso Yoshiaki
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
Bioorg Med Chem Lett. 2003 Dec 15;13(24):4273-6. doi: 10.1016/j.bmcl.2003.09.053.
A novel class of substrate-based beta-secretase (BACE1) inhibitors containing a hydroxymethylcarbonyl (HMC) isostere was designed and synthesized. Phenylnorstatine [(2R,3S)-3-amino-2-hydroxy-4-phenylbutyric acid; Pns] was an effective transition-state mimic at the P(1) position. Structure-activity relationships (SARs) of the P(3)-P(3)' positions of BACE1 inhibitors were studied.
设计并合成了一类新型的含羟甲基羰基（HMC）电子等排体的基于底物的β-分泌酶（BACE1）抑制剂。苯基去甲缬氨酸[（2R，3S）-3-氨基-2-羟基-4-苯基丁酸；Pns]是P(1)位有效的过渡态模拟物。研究了BACE1抑制剂P(3)-P(3)'位的构效关系（SARs）。
