Proof of Concept Study for Designed Multiple Ligands Targeting the Dopamine D2, Serotonin 5-HT2A, and Muscarinic M1 Acetylcholine Receptors

被引：11

作者：

Szabo, Monika ^{[1
]}

Lim, Herman D. ^{[1
]}

Herenbrink, Carmen Klein ^{[1
]}

Christopoulos, Arthur ^{[1
]}

Lane, J. Robert ^{[1
]}

Capuano, Ben ^{[1
]}

机构：

[1] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 03期

基金：

英国医学研究理事会;

关键词：

ALLOSTERIC MODULATORS; AGONIST; DRUGS; ANTIPSYCHOTICS; DISCOVERY; MODES; LEAD;

D O I：

10.1021/jm5013243

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we describe the hybridization of a benzoxazinone M-1 scaffold with D-2 privileged structures derived from putative and clinically relevant antipsychotics to develop designed multiple ligands. The M-1 mAChR is an attractive target for the cognitive deficits in key CNS disorders. Moreover, activity at D-2 and 5-HT2A receptors has proven useful for antipsychotic efficacy. We identified 9 which retained functional activity at the target M-1 mAChR and D2R and demonstrated high affinity for the 5-HT2AR.

引用

页码：1550 / 1555

页数：6

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