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
收藏
页码：1550 / 1555
页数：6
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