Design and Synthesis of an Orally Active Metabotropic Glutamate Receptor Subtype-2 (mGluR2) Positive Allosteric Modulator (PAM) That Decreases Cocaine Self-Administration in Rats

被引：38

作者：

Dhanya, Raveendra-Panickai ^{[1
]}

Sidique, Shyama ^{[1
]}

Sheffler, Douglas J. ^{[2
]}

Nickols, Hilary Highfield ^{[3
]}

Herath, Ananda ^{[1
]}

Yang, Li ^{[1
]}

Dahl, Russell ^{[1
]}

Ardecky, Robert ^{[1
]}

Semenova, Svetlana ^{[4
]}

Markou, Athina

Conn, P. Jeffrey ^{[2
]}

Cosford, Nicholas D. P. ^{[1
]}

机构：

[1] Sanford Burnham Med Res Inst, Apoptosis & Cell Death Res Program, La Jolla, CA 92037 USA

[2] Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA

[4] Univ Calif San Diego, Dept Psychiat, Sch Med, La Jolla, CA 92093 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2011年 / 54卷 / 01期

基金：

美国国家卫生研究院;

关键词：

LONG-TERM POTENTIATION; BRAIN REWARD FUNCTION; AGONIST LY379268; PHARMACOLOGICAL CHARACTERIZATION; GLUTAMATE-RECEPTOR-2; MGLU2; EXTRACELLULAR GLUTAMATE; INDUCED REINSTATEMENT; SEEKING BEHAVIOR; ADDICTION; IDENTIFICATION;

D O I：

10.1021/jm1012165

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The modification of 3'((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1 H-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

引用

页码：342 / 353

页数：12

共 60 条

[1] Pharmacological stimulation of group II metabotropic glutamate receptors reduces cocaine self-administration and cocaine-induced reinstatement of drug seeking in squirrel monkeys [J].

Adewale, A. S. ;

Platt, D. M. ;

Spealman, R. D. .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 318 (02) :922-931

[2] Rats with extended access to cocaine exhibit increased stress reactivity and sensitivity to the anxiolytic-like effects of the mGluR 2/3 agonist LY379268 during abstinence [J].

Aujla, Harinder ;

Martin-Fardon, Remi ;

Weiss, Friedbert .

NEUROPSYCHOPHARMACOLOGY, 2008, 33 (08) :1818-1826

[3] Preferential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on conditioned reinstatement versus primary reinforcement: Comparison between cocaine and a potent conventional reinforcer [J].

Baptista, MAS ;

Martin-Fardon, R ;

Weiss, F .

JOURNAL OF NEUROSCIENCE, 2004, 24 (20) :4723-4727

[4] Biphenyl-indanones: Allosteric potentiators of the metabotropic glutamate subtype 2 receptor [J].

Bonnefous, C ;

Vernier, JM ;

Hutchinson, JH ;

Gardner, MF ;

Cramer, M ;

James, JK ;

Rowe, BA ;

Daggett, LP ;

Schaffhauser, H ;

Kamenecka, TM .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2005, 15 (19) :4354-4358

[5] The mGluR2/3 agonist LY379268 attenuates context- and discrete cue-induced reinstatement of sucrose seeking but not sucrose self-administration in rats [J].

Bossert, Jennifer M. ;

Poles, Gabriela C. ;

Sheffler-Collins, Sean I. ;

Ghitza, Udi E. .

BEHAVIOURAL BRAIN RESEARCH, 2006, 173 (01) :148-152

[6] 3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts [J].

Brnardic, Edward J. ;

Fraley, Mark E. ;

Garbaccio, Robert M. ;

Layton, Mark E. ;

Sanders, John M. ;

Culberson, Chris ;

Jacobson, Marlene A. ;

Magliaro, Brian C. ;

Hutson, Pete H. ;

O'Brien, Julie A. ;

Huszar, Sarah L. ;

Uslaner, Jason M. ;

Fillgrove, Kerry L. ;

Tang, Cuyue ;

Kuo, Yuhsin ;

Sur, Sylvie M. ;

Hartman, George D. .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (10) :3129-3133

[7]

Cacciola J, 2009, Metabotropic Glutamate Receptor lsoxazole Ligands and Their Use as Potentiators, Patent No. [US2009/0306158 A1, 20090306158]

[8] Regulation of neurotransmitter release by metabotropic glutamate receptors [J].

Cartmell, J ;

Schoepp, DD .

JOURNAL OF NEUROCHEMISTRY, 2000, 75 (03) :889-907

[9] Pharmacology and functions of metabotropic glutamate receptors [J].

Conn, PJ ;

Pin, JP .

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1997, 37 :205-237

[10] Novel alternative for the N-S bond formation and its application to the synthesis of benzisothiazol-3-ones [J].

Correa, Arkaitz ;

Tellitu, Imanol ;

Dominguez, Esther ;

SanMartin, Raul .

ORGANIC LETTERS, 2006, 8 (21) :4811-4813

← 1 2 3 4 5 6 →