Synthesis of novel triplet drugs with 1,3,5-trioxazatriquinane skeletons and their pharmacologies. 1: Synthesis of triplet drugs with morphinan skeletons.

Authors :: Nagase H
Watanabe A
Nemoto T
Nakajima M
Hasebe K
Mochizuki H
Fujii H
Source :: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2011 Jul 01; Vol. 21 (13), pp. 4023-6. Date of Electronic Publication: 2011 May 05.
Publication Year :: 2011
Abstract: We synthesized symmetrical and nonsymmetrical triplet drugs with 1,3,5-trioxazatriquinane skeletons. The isolation of key intermediates, oxazoline dimers, made it possible to effectively produce nonsymmetrical triplets. Among the synthesized triplets, KNT-93, composed of three identical opioid μ receptor agonists, showed dose-dependent antinociception via the μ receptor. The effect was 56-fold more potent than that of morphine, a representative μ agonist. The profound analgesic effect induced by KNT-93 might result from simultaneous occupation of three μ opioid receptors.<br /> (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Subjects :: Analgesics chemistry
Bridged-Ring Compounds chemistry
Dose-Response Relationship, Drug
Molecular Structure
Naltrexone chemical synthesis
Naltrexone chemistry
Receptors, Opioid, mu agonists
Analgesics chemical synthesis
Bridged-Ring Compounds chemical synthesis
Morphinans chemistry
Naltrexone analogs & derivatives

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