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Ketamine esters and amides as short-acting anaesthetics: Structure-activity relationships for the side-chain |
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| Authors: | Ivaylo V Dimitrov Martyn G Harvey Logan J Voss James W Sleigh Michael J Bickerdike William A Denny |
| Institution: | 1. Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, New Zealand;2. Waikato Clinical School, University of Auckland, New Zealand;3. Kea Therapeutics Ltd, Auckland, New Zealand |
| Abstract: | 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. |
| Keywords: | DCC DCM dichloromethane DMAP 4-dimethylaminopyridine LDA lithium diisopropylamide LRR loss of righting reflex NMDA PWR pedal withdrawal reflex score TFAA trifluoroacetic acid anhydride Ketamine Esters Anaesthesia Short-acting Structure-activity relationship |
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