Definition of a pharmacophore for partial agonists of serotonin 5-HT3 receptors

被引：34

作者：

Daveu, C ^{[1
]}

Bureau, R ^{[1
]}

Baglin, I ^{[1
]}

Prunier, H ^{[1
]}

Lancelot, JC ^{[1
]}

Rault, S ^{[1
]}

机构：

[1] Univ Caen, Ctr Etud & Rech Medicament Normandie, F-14032 Caen, France

来源：

JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES | 1999年 / 39卷 / 02期

关键词：

D O I：

10.1021/ci980153u

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A definition of a partial agonists serotonin 5-HT3 pharmacophore was carried out by considering a three-dimensional model which correlates the chemical structures of series of piperazinopyrrolothienopyrazines, piperazinopyridopyrrolopyrazines, piperazinopyrroloquinolaxines, piperazinopyridopyrroloquinoxalines, aminoalkyloximinopyrroloindoles, aminoalkyloximinothienopyrrolizines, and aminoalkyloxopyrrolizines with the biological affinities. The model is formed by five features corresponding to two hydrogen bond accepters, one aromatic ring, one hydrophobic group, and one positive ionizable site (quaternary ammonium ions). The nature of the features and the distances between them explain the partial agonist activities of these compounds.

引用

页码：362 / 369

页数：8

共 42 条

[1] 5-HT3 RECEPTOR ANTAGONISTS - AN OVERVIEW OF THEIR PRESENT STATUS AND FUTURE POTENTIAL IN CANCER THERAPY-INDUCED EMESIS [J].

AAPRO, MS .

DRUGS, 1991, 42 (04) :551-568

[2] 2,4-DIAMINO-6,7-DIMETHOXYQUINAZOLINES .2. 2-(4-CARBAMOYLPIPERIDINO) DERIVATIVES AS ALPHA-1-ADRENOCEPTOR ANTAGONISTS AND ANTIHYPERTENSIVE AGENTS [J].

ALABASTER, VA ;

CAMPBELL, SF ;

DANILEWICZ, JC ;

GREENGRASS, CW ;

PLEWS, RM .

JOURNAL OF MEDICINAL CHEMISTRY, 1987, 30 (06) :999-1003

[3]

Allen F.H., 1993, CHEM AUTOMAT NEWS, V8, P31

[4] CRYSTAL-STRUCTURE OF SEROTONIN HYDROGEN OXALATE [J].

AMIT, A ;

MESTER, L ;

KLEWE, B ;

FURBERG, S .

ACTA CHEMICA SCANDINAVICA SERIES A-PHYSICAL AND INORGANIC CHEMISTRY, 1978, 32 (03) :267-270

[5] THE EFFECT OF HYDROGEN-BONDING ON THE CHLOROCUPRATE(II) GEOMETRY - A COMPOUND CONTAINING AN UNUSUAL COPPER CHLORINE RATIO OF 1-6 - CRYSTAL AND MOLECULAR-STRUCTURE OF BIS(N-BENZYLPIPERAZINIUMCHLORIDE)TETRACHLOROCUPRATE(II) [J].

ANTOLINI, L ;

MENABUE, L ;

PELLACANI, GC ;

SALADINI, M ;

MARCOTRIGIANO, G .

INORGANICA CHIMICA ACTA-ARTICLES, 1982, 58 (MAR) :193-200

[6] DIFFERENTIAL BINDING CHARACTERISTICS OF AGONISTS AT 5-HT(3) RECEPTOR RECOGNITION SITES IN NG108-15 NEUROBLASTOMA-GLIOMA CELLS LABELED BY [H-3] (S)-ZACOPRIDE AND [H-3] GRANISETRON [J].

BARNES, JM ;

BARNES, NM .

BIOCHEMICAL PHARMACOLOGY, 1993, 45 (10) :2155-2158

[7] CHARMM - A PROGRAM FOR MACROMOLECULAR ENERGY, MINIMIZATION, AND DYNAMICS CALCULATIONS [J].

BROOKS, BR ;

BRUCCOLERI, RE ;

OLAFSON, BD ;

STATES, DJ ;

SWAMINATHAN, S ;

KARPLUS, M .

JOURNAL OF COMPUTATIONAL CHEMISTRY, 1983, 4 (02) :187-217

[8] Conformational analysis and 3D QSAR study on novel partial agonists of 5-HT3 receptors [J].

Bureau, R ;

Lancelot, JC ;

Prunier, H ;

Rault, S .

QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIPS, 1996, 15 (05) :373-381

[9]

BUTLER A, 1988, BRIT J PHARMACOL, V94, P387

[10] X-RAY CRYSTAL-STRUCTURES OF LOXAPINE[2-CHLORO-11-(4-METHYL-1-PIPERAZINYL)DIBENZ[B,F][1,4]OXAZEPINE] AND AMOXAPINE[2-CHLORO-11-(1-PIPERAZINYL)DIBENZ[B,F][1,4]OXAZEPINE] [J].

COSULICH, DB ;

LOVELL, FM .

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE, 1977, 33 (APR15) :1147-1154

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