Ketamine esters and amides as short-acting anaesthetics: Structure-activity relationships the side-chain

被引：11
|
作者：
Dimitrov, Ivaylo V. [1 ]
Harvey, Martyn G. [2 ]
Voss, Logan J. [2 ]
Sleigh, James W. [2 ]
Bickerdike, Michael J. [3 ]
Denny, William A. [1 ]
机构：
[1] Univ Auckland, Sch Med Sci, Auckland Canc Soc, Res Ctr, Auckland, New Zealand
[2] Univ Auckland, Waikato Clin Sch, Auckland, New Zealand
[3] Kea Therapeut Ltd, Auckland, New Zealand
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 2019年 / 27卷 / 07期
关键词：
Ketamine; Esters; Anaesthesia; Short-acting; Structure-activity relationship;
D O I：
10.1016/j.bmc.2019.02.010
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：
N-Aliphatic ester analogues of the non-opioid ketamine (1) retain effective anaesthetic/analgesic properties while minimising ketamine's psychomimetic side-effects. We show that the anaesthetic/analgesic properties of these ester analogues depend critically on the length (from 2 to 4 carbons), polarity and steric cross-section of the aliphatic linker chain. More stable amide and ethylsulfone analogues generally showed weaker anaesthetic/analgesic activity. There was no correlation between the anaesthetic/analgesic properties of the compounds and their binding affinities for the N-methyl-D-aspartate (NMDA) receptor.
引用
收藏
页码：1226 / 1231
页数：6
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