当前位置: X-MOL 学术J. Med. Chem. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Subtle Modifications to the Indole-2-carboxamide Motif of the Negative Allosteric Modulator N-((trans)-4-(2-(7-Cyano-3,4-dihydroisoquinolin-2(1H)-yl)ethyl)cyclohexyl)-1H-indole-2-carboxamide (SB269652) Yield Dramatic Changes in Pharmacological Activity at the Dopamine D2 Receptor
Journal of Medicinal Chemistry ( IF 7.3 ) Pub Date : 2018-06-11 00:00:00 , DOI: 10.1021/acs.jmedchem.8b00192
Anitha Kopinathan , Christopher Draper-Joyce , Monika Szabo , Arthur Christopoulos , Peter J. Scammells , J. Robert Lane , Ben Capuano

SB269652 (1) is a negative allosteric modulator of the dopamine D2 receptor. Herein, we present the design, synthesis, and pharmacological evaluation of “second generation” analogues of 1 whereby subtle modifications to the indole-2-carboxamide motif confer dramatic changes in functional affinity (5000-fold increase), cooperativity (100-fold increase), and a novel action to modulate dopamine efficacy. Thus, structural changes to this region of 1 allows the generation of a novel set of analogues with distinct pharmacological properties.

中文翻译:

负变构调节剂N -((反式)-4-(2-(7-氰基-3,4-二氢异喹啉-2(1 H)-基)乙基)环己基的吲哚-2-羧酰胺基团的细微修饰-1 H-吲哚-2-羧酰胺(SB269652)在多巴胺D 2受体上的药理活性产生显着变化

SB269652(1)是多巴胺D 2受体的负变构调节剂。本文中,我们介绍了1的“第二代”类似物的设计,合成和药理学评估,其中对吲哚-2-羧酰胺基序的微妙修饰赋予了功能亲和力(增加了5000倍),协同性(增加了100倍) ),以及调节多巴胺功效的新作用。因此,对该区域1的结构变化允许产生具有不同药理学性质的一组新的类似物。
更新日期:2018-06-11
down
wechat
bug