当前位置： SCI文献检索 > JOURNAL OF MEDICINAL CHEMISTRY期刊下所有文献 > Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats.

Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats.

Abstract：

:The modification of 3'-((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1H-inden-5-yloxy)methyl)biphenyl-4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and superior druglike properties. These analogues are more potent than 1 in vitro and are highly selective for mGluR2 vs other mGluR subtypes. They have significantly improved pharmacokinetic (PK) properties, with excellent oral bioavailability and brain penetration. The benzisothiazol-3-one derivative 14 decreased cocaine self-administration in rats, providing proof-of-concept for the use of mGluR2 PAMs for the treatment of cocaine dependence.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Dhanya RP,Sidique S,Sheffler DJ,Nickols HH,Herath A,Yang L,Dahl R,Ardecky R,Semenova S,Markou A,Conn PJ,Cosford ND

doi

10.1021/jm1012165

subject

Has Abstract

pub_date

2011-01-13 00:00:00

pages

342-53

issue

1

eissn

0022-2623

issn

1520-4804

journal_volume

54

pub_type

杂志文章

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