Synthesis and Enantiomeric Resolution of Medetomidine

Fakhraian, Hossein; Toulabi, H.; Choobdari, Ebrahim; Peyrovi, M. H.; Ghanbary, H. Hadj

doi:10.1080/00304948.2015.1005985

Cited by 3 publications

(2 citation statements)

References 16 publications

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“…Preparation of azimedetomidine was accomplished using a modification of a recent procedure for the efficient synthesis of medetomidine. 14 Treatment of the previously reported 15 alcohol 2 (Figure 1, bottom) with a mixture of (N-(trimethylsilyl)imidazole and titanium tetrachloride under reflux in methylene chloride produced azi-medetomidine (azi-medetomidine, 1, Figure 1) in 40% yield after workup and purification. It is noteworthy that the trifluoromethyldiazirine group survives intact under these strongly acidic conditions.…”

Section: ■ Results and Discussionmentioning

confidence: 98%

“…This strategy was used to minimize possible steric interactions between the diazirine group and the removed methyl group as well as for synthetic convenience. Preparation of azi-medetomidine was accomplished using a modification of a recent procedure for the efficient synthesis of medetomidine . Treatment of the previously reported alcohol 2 (Figure , bottom) with a mixture of ( N -(trimethylsilyl)imidazole and titanium tetrachloride under reflux in methylene chloride produced azi-medetomidine (azi-medetomidine, 1 , Figure ) in 40% yield after workup and purification.…”

Section: Resultsmentioning

confidence: 99%

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Azi-medetomidine: Synthesis and Characterization of a Novel α2 Adrenergic Photoaffinity Ligand

McKinstry-Wu

Woll

Joseph

et al. 2019

ACS Chem. Neurosci.

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Agonists at the α2 adrenergic receptor produce sedation, increase focus, provide analgesia, and induce centrally mediated hypotension and bradycardia, yet neither their dynamic interactions with adrenergic receptors nor their modulation of neuronal circuit activity is completely understood. Photoaffinity ligands of α2 adrenergic agonists have the potential both to capture discrete moments of ligand–receptor interactions and to prolong naturalistic drug effects in discrete regions of tissue in vivo. We present here the synthesis and characterization of a novel α2 adrenergic agonist photolabel based on the imidazole medetomidine called azi-medetomidine. Azi-medetomidine shares protein association characteristics with its parent compound in experimental model systems and by molecular dynamics simulation of interactions with the α2A adrenergic receptor. Azi-medetomidine acts as an agonist at α2A adrenergic receptors, and produces hypnosis in Xenopus laevis tadpoles. Azi-medetomidine competes with the α2 agonist clonidine at α2A adrenergic receptors, which is potentiated by photolabeling, and azi-medetomidine labels moieties on the α2A adrenergic receptor as determined by mass spectrometry in a manner consistent with a simulated model. This novel α2 adrenergic agonist photolabel can serve as a powerful tool for in vitro and in vivo investigations of adrenergic signaling.

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Section: ■ Results and Discussionmentioning

confidence: 98%

Section: Resultsmentioning

confidence: 99%