The influence of an ethylene spacer on the 5-HT1A and 5-HT2A receptor affinity of arylpiperazine derivatives of amides with N-acylated amino acids and 3-differently substituted pyrrolidine-2,5-diones

被引：7

作者：

Zajdel, Pawel ^{[1
]}

Subra, Gilles ^{[2
]}

Verdie, Pascal ^{[2
]}

Bojarski, Andrzej J. ^{[3
]}

Duszynska, Beata ^{[3
]}

Basista, Katarzyna ^{[1
]}

Obniska, Jolanta ^{[1
]}

Martinez, Jean ^{[2
]}

Pawlowski, Maciej ^{[1
]}

机构：

[1] Jagiellonian Univ, Coll Med, Dept Med Chem, PL-30688 Krakow, Poland

[2] Univ Montpellier I & II, Fac Pharm, CNRS, UMR 5247,Inst Biomol Max Mousseron, F-34060 Montpellier, France

[3] Polish Acad Sci, Inst Pharmacol, Dept Med Chem, PL-31343 Krakow, Poland

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 44卷 / 02期

关键词：

Long-chain arylpiperazines; Succinimides; Spirosuccinimides; Pyrrolidine-2,5-dione; 2-Azaspiro[4.5]decane-1,3-dione; Pyrrolidine-5-one-carboxamide; Prolinamides; Solid-phase synthesis; 5-HT1A/5-HT2A receptor ligands; DRUG; DEPRESSION; DISCOVERY; CHEMISTRY; LIGANDS; AGONIST;

D O I：

10.1016/j.ejmech.2008.05.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A library of ethylene analogs of the previously described arylpiperazines with N-acylated amino acids was synthesized on SynPhase (TM) Lanterns and the library representatives were evaluated for their 5-HT1A and 5-HT2A receptor affinities. The obtained results were compared with those reported for compounds containing propylene and a butylene spacer and they revealed that 5-HT1A receptor affinity decreased proportionally with the length of the alkyl chain. Furthermore, the synthesized 3-cycloalkyl derivatives containing two methylene group spacers (20, 21) showed that the 3-position of pyrrolidine-2,5-dione preferred substituents of hydrophobic character. (c) 2008 Elsevier Masson SAS. All rights reserved.

引用

页码：800 / 808

页数：9

共 16 条

[1] An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression [J].

Becker, Oren M. ;

Dhanoa, Dale S. ;

Marantz, Yael ;

Chen, Dongli ;

Shacham, Sharon ;

Cheruku, Srinivasa ;

Heifetz, Alexander ;

Mohanty, Pradyumna ;

Fichman, Merav ;

Sharadendu, Anurag ;

Nudelman, Raphael ;

Kauffman, Michael ;

Noiman, Silvia .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (11) :3116-3135

[2]

BOJARSKI AJ, 1993, PHARMAZIE, V48, P289

[3]

CHENG Y, 1973, BIOCHEM PHARMACOL, V22, P3099

[4]

de Paulis T, 2007, IDRUGS, V10, P193

[5] Buspirone - An updated review of its clinical pharmacology and therapeutic applications [J].

Fulton, B ;

Brogden, RN .

CNS DRUGS, 1997, 7 (01) :68-88

[6] ARYLPIPERAZINE DERIVATIVES AS HIGH-AFFINITY 5-HT1A SEROTONIN LIGANDS [J].

GLENNON, RA ;

NAIMAN, NA ;

LYON, RA ;

TITELER, M .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (10) :1968-1971

[7] Application of combinatorial chemistry science on modern drug discovery [J].

Kennedy, J. Phillip ;

Williams, Lyndsey ;

Bridges, Thomas M. ;

Daniels, R. Nathan ;

Weaver, David ;

Lindsley, Craig W. .

JOURNAL OF COMBINATORIAL CHEMISTRY, 2008, 10 (03) :345-354

[8]

KIKUCHI T, 1995, J PHARMACOL EXP THER, V274, P329

[9] ANTICONVULSANTS .1. AN INVESTIGATION OF N-R-ALPHA-R1-ALPHA-PHENYLSUCCINIMIDES [J].

MILLER, CA ;

LONG, LM .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1951, 73 (10) :4895-4898

[10]

Newman-Tancredi A, 2007, CURR OPIN INVEST DR, V8, P539

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