Selective κ-opioid antagonists related to naltrindole.: Effect of side-chain spacer in the 5′-amidinoalkyl series

被引：12

作者：

Jales, AR ^{[1
]}

Husbands, SM ^{[1
]}

Lewis, JW ^{[1
]}

机构：

[1] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 20期

关键词：

D O I：

10.1016/S0960-894X(00)00433-9

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The study of kappa -opioid receptor function in vivo has been hampered by the limited choice of selective kappa -antagonists. Recently discovered cc-antagonists have not yet been utilised in vivo. We here report the synthesis and in vitro evaluation of a new amidine derivative of naltrindole. It showed substantially greater kappa -selectivity in binding assays than known analogues with shorter spacer in the amidine side chain. This indicates that in nor-BNI and related selective kappa -antagonists, the second basic centre may not be ideally located. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：2259 / 2261

页数：3

共 10 条

[1]

BUTELMAN ER, 1993, J PHARMACOL EXP THER, V267, P1269

[2] Mutational evidence for a common κ antagonist binding pocket in the wild-type κ and mutant μ[K303E] opioid receptors [J].

Jones, RM ;

Hjorth, SA ;

Schwartz, TW ;

Portoghese, PS .

JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (25) :4911-4914

[3] SYNTHESIS AND KAPPA-OPIOID ANTAGONIST SELECTIVITY OF A NORBINALTORPHIMINE CONGENER - IDENTIFICATION OF THE ADDRESS MOIETY REQUIRED FOR KAPPA-ANTAGONIST ACTIVITY [J].

LIN, CE ;

TAKEMORI, AE ;

PORTOGHESE, PS .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (16) :2412-2415

[4] A REMARKABLE CHANGE OF OPIOID RECEPTOR SELECTIVITY ON THE ATTACHMENT OF A PEPTIDOMIMETIC KAPPA ADDRESS ELEMENT TO THE DELTA ANTAGONIST, NATRINDOLE - 5'-[(N-2-ALKYLAMIDINO)METHYL]NALTRINDOLE DERIVATIVES AS A NOVEL CLASS OF KAPPA OPIOID RECEPTOR ANTAGONISTS [J].

OLMSTED, SL ;

TAKEMORI, AE ;

PORTOGHESE, PS .

JOURNAL OF MEDICINAL CHEMISTRY, 1993, 36 (01) :179-180

[5] STEREOCHEMICAL STUDIES ON MEDICINAL AGENTS .31. ONLY ONE PHARMACOPHORE IS REQUIRED FOR THE K-OPIOID ANTAGONIST SELECTIVITY OF NORBINALTORPHIMINE [J].

PORTOGHESE, PS ;

NAGASE, H ;

TAKEMORI, AE .

JOURNAL OF MEDICINAL CHEMISTRY, 1988, 31 (07) :1344-1347

[6]

REYNAUD P, 1964, B SOC CHIM FR, P2997

[7]

SCHWYZER R, 1977, ANN NY ACAD SCI, V247, P3

[8]

Toll L, 1998, NIDA Res Monogr, V178, P440

[9]

TRAYNOR JR, 1995, MOL PHARMACOL, V47, P848

[10]

WINCHESTER MJ, 1975, J HETEROCYCLIC CHEM, V83, P547

← 1 →