Discovery of a new series of 5-HT1A receptor agonists

被引：23

作者：

Franchini, Silvia ^{[1
]}

Prandi, Adolfo ^{[1
]}

Sorbi, Claudia ^{[1
]}

Tait, Annalisa ^{[1
]}

Baraldi, Annamaria ^{[1
]}

Angeli, Piero ^{[2
]}

Buccioni, Michela ^{[2
]}

Cilia, Antonio ^{[3
]}

Poggesi, Elena ^{[3
]}

Fossa, Paola ^{[4
]}

Brasili, Livio ^{[1
]}

机构：

[1] Univ Modena & Reggio Emilia, Dipartimento Sci Farmaceut, I-41100 Modena, Italy

[2] Univ Camerino, Dipartimento Sci Chim, I-62032 Camerino, Italy

[3] Recordati SpA, Div Ric & Sviluppo, I-20148 Milan, Italy

[4] Univ Genoa, Dipartimento Sci Farmaceut, I-16132 Genoa, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 06期

关键词：

5-HT1A receptor; Agonists; 1,3-Dioxolane; Selectivity; 1,3-DIOXOLANE-BASED LIGANDS; ANTAGONISTS; DEPRESSION; ANXIETY; POTENT;

D O I：

10.1016/j.bmcl.2010.01.030

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Starting from compounds previously identified as alpha(1)-adrenoceptor antagonists that were also found to bind to the 5-HT1A receptor, in an attempt to separate the two activities, a new series of 5-HT1A receptor agonists was identified and shown to have high potency and/or high selectivity. Of these, compound 13, which combines high selectivity (5-HT1A/alpha(1) = 151) and good agonist potency (pD(2) = 7.82; E-max = 76), was found to be the most interesting. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：2017 / 2020

页数：4

共 17 条

[1]

ANGELI P, 1985, EUR J MED CHEM, V20, P517

[2] 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

[3]

Berends AC, 2005, CNS DRUG REV, V11, P379

[4] 1,3-dioxolane-based ligands as a novel class of α1-adrenoceptor antagonists [J].

Brasili, L ;

Sorbi, C ;

Franchini, S ;

Manicardi, M ;

Angeli, P ;

Marucci, G ;

Leonardi, A ;

Poggesi, E .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (08) :1504-1511

[5] Derivatives as 5HT1A receptor ligands -: Past and present [J].

Caliendo, G ;

Santagada, V ;

Perissutti, E ;

Fiorino, F .

CURRENT MEDICINAL CHEMISTRY, 2005, 12 (15) :1721-1753

[6]

Colpaert FC, 2006, CURR OPIN INVEST DR, V7, P40

[7] Towards a new generation of potential antipsychotic agents combining D2 and 5-HT1A receptor activities [J].

Cuisiat, Stephane ;

Bourdiol, Nathalie ;

Lacharme, Vincent ;

Newman-Tancredi, Adrian ;

Colpaert, Francis ;

Vacher, Bernard .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (04) :865-876

[8]

De Vry J, 1992, SEROTONIN 1A RECEPTO, P55

[9]

DEVRY J, 1995, PSYCHOPHARMACOLOGY, P121

[10] (2,2-Diphenyl-[1,3]oxathiolan-5-ylmethyl)-(3-phenyl-propyl)-amine: a Potent and Selective 5-HT1A Receptor Agonist [J].

Franchini, Silvia ;

Tait, Annalisa ;

Prandi, Adolfo ;

Sorbi, Claudia ;

Gallesi, Rossella ;

Buccioni, Michela ;

Marucci, Gabriella ;

De Stefani, Carla ;

Cilia, Antonio ;

Brasili, Livio .

CHEMMEDCHEM, 2009, 4 (02) :196-203

← 1 2 →