Anionic cyclophanes as potential reversal agents of muscle relaxants by chemical chelation

被引：24

作者：

Cameron, KS

Fielding, L

Mason, R

Muir, AW

Rees, DC

Thorn, S

Zhang, MQ

机构：

[1] Organon Res Labs Ltd, Dept Med Chem, Newhouse ML1 5SH, Lanark, Scotland

[2] Organon Res Labs Ltd, Dept Pharmacol, Newhouse ML1 5SH, Lanark, Scotland

[3] Organon Res Labs Ltd, Dept Analyt Chem, Newhouse ML1 5SH, Lanark, Scotland

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2002年 / 12卷 / 05期

关键词：

D O I：

10.1016/S0960-894X(02)00017-3

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of carboxyl-containing cyclophanes have been designed and synthesised as chemical chelators (or host molecules) of cationic muscle relaxant drugs (or guest molecules). Three of these cyclophane derivatives, 1-3, have been shown by NMR to form 1:1 complexes with the muscle relaxants pancuronium. 4 and gallamine, 5 in D2O, with association constants up to 10(4) M-1. When tested in an in vitro chick biventer muscle preparation, the cyclophanes reversed the neuromuscular block induced by pancuronium and gallamine, with 3 having the most effective reversal against pancuronium (EC50 40 muM). (C) 2002 Elsevier Science Ltd. All rights reserved.

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页码：753 / 755

页数：3

相关论文

共 20 条

[11] Measurement of molecular association in drug:cyclodextrin inclusion complexes with improved H-1 NMR studies [J].

Loukas, YL .

JOURNAL OF PHARMACY AND PHARMACOLOGY, 1997, 49 (10) :944-948

[12]

MERIC R, 1994, B SOC CHIM FR, V131, P579

[13] SPONTANEOUS-RECOVERY OR EVOKED REVERSAL OF NEUROMUSCULAR BLOCK [J].

MIRAKHUR, RK .

ACTA ANAESTHESIOLOGICA SCANDINAVICA, 1995, 39 :62-65

[14] SUBSTRATE SELECTIVE INCLUSION BY A SERIES OF WATER-SOLUBLE PARACYCLOPHANES - HOST-GUEST RECOGNITION OF STERIC STRUCTURE AND CHARGE [J].

ODASHIMA, K ;

SOGA, T ;

KOGA, K .

TETRAHEDRON LETTERS, 1981, 22 (52) :5311-5314

[15] CAVITY DEPTH AND WIDTH EFFECTS ON CYCLOPHANE-STEROID RECOGNITION - MOLECULAR COMPLEXATION OF CHOLESTEROL AND PROGESTERONE IN AQUEOUS-SOLUTION [J].

PETERSON, BR ;

MORDASINIDENTI, T ;

DIEDERICH, F .

CHEMISTRY & BIOLOGY, 1995, 2 (03) :139-146

[16] STEROID COMPLEXATION BY CYCLOPHANE RECEPTORS IN AQUEOUS-SOLUTION - SUBSTRATE SELECTIVITY, ENTHALPIC DRIVING-FORCE FOR CAVITY INCLUSION, AND ENTHALPY-ENTROPY COMPENSATION [J].

PETERSON, BR ;

WALLIMANN, P ;

CARCANAGUE, DR ;

DIEDERICH, F .

TETRAHEDRON, 1995, 51 (02) :401-421

[17]

PETERSON BR, 1994, ANGEW CHEM INT EDIT, V33, P1625, DOI 10.1002/anie.199416251

[18] HYDROPHOBIC BINDING OF WATER-SOLUBLE GUESTS BY HIGH-SYMMETRY, CHIRAL HOSTS - AN ELECTRON-RICH RECEPTOR-SITE WITH A GENERAL AFFINITY FOR QUATERNARY AMMONIUM-COMPOUNDS AND ELECTRON-DEFICIENT PI-SYSTEMS [J].

PETTI, MA ;

SHEPODD, TJ ;

BARRANS, RE ;

DOUGHERTY, DA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (20) :6825-6840

[19] HOST-GUEST CHEMISTRY .6. A MACROBICYCLIC POLYPHENOXIDE AS RECEPTOR ANALOG FOR CHOLINE AND RELATED AMMONIUM-COMPOUNDS [J].

SCHNEIDER, HJ ;

GUTTES, D ;

SCHNEIDER, U .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION IN ENGLISH, 1986, 25 (07) :647-649

[20] Dendrophanes: Novel steroid-recognizing dendritic receptors [J].

Wallimann, P ;

Seiler, P ;

Diederich, F .

HELVETICA CHIMICA ACTA, 1996, 79 (03) :779-788