Sall D J, Arfsten A E, Bastian J A, Denney M L, Harms C S, McCowan J R, Morin J M, Rose J W, Scarborough R M, Smyth M S, Um S L, Utterback B G, Vasileff R T, Wikel J H, Wyss V L, Jakubowski J A
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Med Chem. 1997 Aug 29;40(18):2843-57. doi: 10.1021/jm970020k.
The use of 5,6-bicyclic amidines as arginine surrogates in the design of a novel class of potent platelet glycoprotein IIb-IIIa receptor (GPIIb-IIIa) antagonists is described. The additional conformational restriction offered by the bicyclic nucleus results in 20-400-fold increases in potency compared to the freely flexible, acyclic benzamidine counterpart. The design, synthesis, structure-activity relationships (SAR), and in vitro activity of this novel class of GPIIb-IIIa antagonists are presented.
本文描述了在新型强效血小板糖蛋白IIb-IIIa受体（GPIIb-IIIa）拮抗剂设计中使用5,6-双环脒作为精氨酸替代物的情况。与自由灵活的无环苯甲脒类似物相比，双环核提供的额外构象限制导致活性提高了20至400倍。本文还介绍了这类新型GPIIb-IIIa拮抗剂的设计、合成、构效关系（SAR）和体外活性。
