An investigation of the N-demethylation of 3-deoxymorphine and the affinity of the alkylation products to μ, δ, and κ receptors

被引：19

作者：

Csutoras, C

Zhang, A

Bidlack, JM

Neumeyer, JL

机构：

[1] Harvard Univ, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA

[2] Univ Rochester, Sch Med & Dent, Dept Pharmacol & Physiol, Rochester, NY 14642 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 10期

关键词：

morphine; codeine; N-demethylation; opioid receptors; binding affinity;

D O I：

10.1016/j.bmc.2004.03.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The N-demethylation of 3-deoxymorphine (1) was investigated using methyl chloroformate and hydrazine. 3-Deoxynormorphine (2) was obtained in 70% yield, and 3-deoxydihydronormorphine (3) was also obtained as a side product. The mu, delta, and kappa receptor binding affinity of a series of N-substituted 3-deoxynormorphines 6 and 7 and N-substituted 3-deoxydihydronormorphines 8-11 was also determined. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2687 / 2690

页数：4

相关论文

共 20 条

[11] REDUCTION OF MONOHALOGENATED NITROBENZENES WITH HYDRAZINE AND RANEY NICKEL - A CONVENIENT PREPARATION OF HALOGENATED ANILINES [J].

LEGGETTER, BE ;

BROWN, RK .

CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1960, 38 (12) :2363-2366

[12] Efficient N-demethylation of opiate alkaloids using a modified nonclassical Polonovski reaction [J].

McCamley, K ;

Ripper, JA ;

Singer, RD ;

Scammells, PJ .

JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (25) :9847-9850

[13] REACTIONS OF THEBAINE WITH AZODICARBOXYLATE ESTERS [J].

MERZ, H ;

POOK, KH .

TETRAHEDRON, 1970, 26 (07) :1727-&

[14] Design and synthesis of novel dimeric morphinan ligands for κ and μ opioid receptors [J].

Neumeyer, JL ;

Zhang, A ;

Xiong, WN ;

Gu, XH ;

Hilbert, JE ;

Knapp, BI ;

Negus, SS ;

Mello, NK ;

Bidlack, JM .

JOURNAL OF MEDICINAL CHEMISTRY, 2003, 46 (24) :5162-5170

[15]

POHLAND A, 1967, Patent No. 3342824

[16] DEOXYMORPHINES - ROLE OF THE PHENOLIC HYDROXYL IN ANTINOCICEPTION AND OPIATE RECEPTOR INTERACTIONS [J].

REDEN, J ;

REICH, MF ;

RICE, KC ;

JACOBSON, AE ;

BROSSI, A ;

STREATY, RA ;

KLEE, WA .

JOURNAL OF MEDICINAL CHEMISTRY, 1979, 22 (03) :256-259

[17] PROCEDURAL REFINEMENTS IN N-DEMETHYLATION OF MORPHINE AND CODEINE USING PHENYL CHLOROFORMATE AND HYDRAZINE [J].

RICE, KC ;

MAY, EL .

JOURNAL OF HETEROCYCLIC CHEMISTRY, 1977, 14 (04) :665-666

[18] IMPROVED PROCEDURE FOR N-DEMETHYLATION OF 6,7-BENZOMORPHANS, MORPHINE, AND CODEINE [J].

RICE, KC .

JOURNAL OF ORGANIC CHEMISTRY, 1975, 40 (12) :1850-1851

[19]

von Braun J, 1909, BER DTSCH CHEM GES, V42, P2035

[20] 10-ketomorphinan and 3-substituted-3-desoxymorphinan analogues as mixed κ and μ opioid ligands:: Synthesis and biological evaluation of their binding affinity at opioid receptors [J].

Zhang, A ;

Xiong, WN ;

Bidlack, JM ;

Hilbert, JE ;

Knapp, BI ;

Wentland, MP ;

Neumeyer, JL .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (01) :165-174