BIVALENT INDOLES EXHIBITING SEROTONERGIC BINDING-AFFINITY

被引：26

作者：

LEBOULLUEC, KL

MATTSON, RJ

MAHLE, CD

MCGOVERN, RT

NOWAK, HP

GENTILE, AJ

机构：

[1] Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1995年 / 5卷 / 02期

关键词：

D O I：

10.1016/0960-894X(94)00470-Z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of bis-5-carboxamidoindoles were prepared and examined in a number of serotonin assays (5HT(1A), 5HT(1D), 5HT(1E), and 5HT UT).(1) They were found to exhibit good affinity for the 5HT(1A) and 5HT(1D) receptor subtypes and to inhibit the 5HT uptake sites. Optimal 5HT(1D) potency was achieved for bivalent analogs 5f and 5g, whose linkers spanned 7 and 8 alkyl units. Analogs with longer alkyl chain linkers (n= 10, 12), 5h and 5i, exhibited no selectivity for the 5HT(1D) receptor over the 5HT(1A) receptor.

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页码：123 / 126

页数：4

相关论文

共 19 条

[1] 7-AMINO-5,6,7,8-TETRAHYDROQUINOLINES - PREPARATION FROM 5,6-DIHYDROQUINOLINE AND NITROGEN NUCLEOPHILES [J].

CLIFFE, IA ;

IFILL, AD ;

MANSELL, HL ;

TODD, RS ;

WHITE, AC .

TETRAHEDRON LETTERS, 1991, 32 (46) :6789-6792

[2]

COLOTTA V, 1991, FARMACO, V46, P1139

[3] NARCOTIC ANTAGONISTIC POTENCY OF BIVALENT LIGANDS WHICH CONTAIN BETA-NALTREXAMINE - EVIDENCE FOR BRIDGING BETWEEN PROXIMAL RECOGNITION SITES [J].

EREZ, M ;

TAKEMORI, AE ;

PORTOGHESE, PS .

JOURNAL OF MEDICINAL CHEMISTRY, 1982, 25 (07) :847-849

[4]

HEURING RE, 1987, J NEUROSCI, V7, P894

[5] SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF A SERIES OF PENICILLIN-DERIVED HIV PROTEINASE-INHIBITORS CONTAINING A STEREOCHEMICALLY UNIQUE PEPTIDE ISOSTERE [J].

HOLMES, DS ;

BETHELL, RC ;

CAMMACK, N ;

CLEMENS, IR ;

KITCHIN, J ;

MCMEEKIN, P ;

MO, CL ;

ORR, DC ;

PATEL, B ;

PATERNOSTER, IL ;

STORER, R .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (21) :3129-3136

[6] EFFECT OF A SPECIFIC 5-HT UPTAKE INHIBITOR, CITALOPRAM (LU 10-171), ON H-3-5-HT UPTAKE IN RAT-BRAIN SYNAPTOSOMES INVITRO [J].

HYTTEL, J .

PSYCHOPHARMACOLOGY, 1978, 60 (01) :13-18

[7]

JANSSEN PAJ, 1991, DRUG INVEST S1, V3, P1

[8]

KALYANAM N, 1992, INDIAN J CHEM B, V31, P243

[9] DETECTION OF A NOVEL SEROTONIN RECEPTOR SUBTYPE (5-HT1E) IN HUMAN-BRAIN - INTERACTION WITH A GTP-BINDING PROTEIN [J].

LEONHARDT, S ;

HERRICKDAVIS, K ;

TITELER, M .

JOURNAL OF NEUROCHEMISTRY, 1989, 53 (02) :465-471

[10] COEXPRESSION STUDIES WITH MUTANT MUSCARINIC ADRENERGIC-RECEPTORS PROVIDE EVIDENCE FOR INTERMOLECULAR CROSS-TALK BETWEEN G-PROTEIN-LINKED RECEPTORS [J].

MAGGIO, R ;

VOGEL, Z ;

WESS, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (07) :3103-3107