SYNTHESIS, LIGAND-BINDING, QSAR, AND COMFA STUDY OF 3-BETA-(PARA-SUBSTITUTED PHENYL)TROPANE-2-BETA-CARBOXYLIC ACID METHYL-ESTERS

被引：203

作者：

CARROLL, FI ^{[1
]}

GAO, YG ^{[1
]}

RAHMAN, MA ^{[1
]}

ABRAHAM, P ^{[1
]}

PARHAM, K ^{[1
]}

LEWIN, AH ^{[1
]}

BOJA, JW ^{[1
]}

KUHAR, MJ ^{[1
]}

机构：

[1] NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 09期

关键词：

D O I：

10.1021/jm00113a008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 3-beta-(p-substituted phenyl)tropane-2-beta-carboxylic acid methyl esters (2) were synthesized and found to possess high affinity for the cocaine binding site in rat striatum. The p-chloro (2c) and p-iodo (2n) compounds, which were the most potent analogues prepared, were found to be 85 and 78 times more potent than (-)-cocaine. The p-bromo (2m) and p-methyl (2d) were also 56 and 60 times more potent than cocaine. QSAR and CoMFA studies were conducted to correlate binding affinity of the cocaine analogues with their structural features. Whereas the QSAR study gave relatively low correlations, the CoMFA study gave a correlation with high predictive value.

引用

页码：2719 / 2725

页数：7

共 17 条

[1]

BERMAN J, 1989, J PHARMACOL EXP THER, V251, P150

[2] NEW, POTENT COCAINE ANALOGS - LIGAND-BINDING AND TRANSPORT STUDIES IN RAT STRIATUM [J].

BOJA, JW ;

CARROLL, FI ;

RAHMAN, MA ;

PHILIP, A ;

LEWIN, AH ;

KUHAR, MJ .

EUROPEAN JOURNAL OF PHARMACOLOGY, 1990, 184 (2-3) :329-332

[3] SYNTHESIS AND LIGAND-BINDING OF COCAINE ISOMERS AT THE COCAINE RECEPTOR [J].

CARROLL, FI ;

LEWIN, AH ;

ABRAHAM, P ;

PARHAM, K ;

BOJA, JW ;

KUHAR, MJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1991, 34 (03) :883-886

[4] COMPOUNDS AFFECTING CENTRAL NERVOUS-SYSTEM .4. 3BETA-PHENYLTROPANE-2-CARBOXYLIC ESTERS AND ANALOGS [J].

CLARKE, RL ;

DAUM, SJ ;

GAMBINO, AJ ;

ACETO, MD ;

PEARL, J ;

LEVITT, M ;

CUMISKEY, WR ;

BOGADO, EF .

JOURNAL OF MEDICINAL CHEMISTRY, 1973, 16 (11) :1260-1267

[5] COMPARATIVE MOLECULAR-FIELD ANALYSIS (COMFA) .1. EFFECT OF SHAPE ON BINDING OF STEROIDS TO CARRIER PROTEINS [J].

CRAMER, RD ;

PATTERSON, DE ;

BUNCE, JD .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (18) :5959-5967

[6] THE DEVELOPMENT AND USE OF QUANTUM-MECHANICAL MOLECULAR-MODELS .76. AM1 - A NEW GENERAL-PURPOSE QUANTUM-MECHANICAL MOLECULAR-MODEL [J].

DEWAR, MJS ;

ZOEBISCH, EG ;

HEALY, EF ;

STEWART, JJP .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1985, 107 (13) :3902-3909

[7] PARABOLIC DEPENDENCE OF DRUG ACTION UPON LIPOPHILIC CHARACTER AS REVEALED BY A STUDY OF HYPNOTICS [J].

HANSCH, C ;

STEWARD, AR ;

ANDERSON, SM ;

BENTLEY, D .

JOURNAL OF MEDICINAL CHEMISTRY, 1968, 11 (01) :1-&

[8] AROMATIC SUBSTITUENT CONSTANTS FOR STRUCTURE-ACTIVITY CORRELATIONS [J].

HANSCH, C ;

LEO, A ;

UNGER, SH ;

KIM, KH ;

NIKAITANI, D ;

LIEN, EJ .

JOURNAL OF MEDICINAL CHEMISTRY, 1973, 16 (11) :1207-1216

[9]

Hansch C., 1979, SUBSTITUENT CONSTANT

[10] THE CRYSTAL-STRUCTURE OF FREE BASE COCAINE, C17H21NO4 [J].

HRYNCHUK, RJ ;

BARTON, RJ ;

ROBERTSON, BE .

CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1983, 61 (03) :481-487

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