4'-(2-呋喃基)-N-吡啶-3-基-4,5'-联嘧啶-2'-胺（LAS38096）的发现与特性，一种强效、选择性且有效的A2B腺苷受体拮抗剂。

Discovery and characterization of 4'-(2-furyl)-N-pyridin-3-yl-4,5'-bipyrimidin-2'-amine (LAS38096), a potent, selective, and efficacious A2B adenosine receptor antagonist.

作者信息

Vidal Bernat, Nueda Arsenio, Esteve Cristina, Domenech Teresa, Benito Sonia, Reinoso Raquel F, Pont Mercè, Calbet Marta, López Rosa, Cadavid María Isabel, Loza María Isabel, Cárdenas Alvaro, Godessart Núria, Beleta Jorge, Warrellow Graham, Ryder Hamish

机构信息

Almirall Research Center, Almirall, Ctra. Laureà Miró 408, E-08980 St. Feliu de Llobregat, Barcelona, Spain.

出版信息

J Med Chem. 2007 May 31;50(11):2732-6. doi: 10.1021/jm061333v. Epub 2007 May 1.

DOI:10.1021/jm061333v

PMID:17469811

Abstract

A novel series of N-heteroaryl 4'-(2-furyl)-4,5'-bipyrimidin-2'-amines has been identified as potent and selective A(2B) adenosine receptor antagonists. In particular, compound 5 showed high affinity for the A(2B) receptor (Ki = 17 nM), good selectivity (IC(50): A(1) > 1000 nM, A(2A) > 2500 nM, A3 > 1000 nM), displayed a favorable pharmacokinetic profile in preclinical species, and showed efficacy in functional in vitro models.

摘要

一系列新型的N-杂芳基4'-(2-呋喃基)-4,5'-联嘧啶-2'-胺已被鉴定为强效且选择性的A(2B)腺苷受体拮抗剂。特别是，化合物5对A(2B)受体表现出高亲和力（Ki = 17 nM），具有良好的选择性（IC(50)：A(1) > 1000 nM，A(2A) > 2500 nM，A3 > 1000 nM），在临床前物种中显示出良好的药代动力学特征，并在体外功能模型中显示出疗效。