Idazoxan
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| Routes of administration | Oral |
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| Formula | C11H12N2O2 |
| Molar mass | 204.229g·mol−1 |
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| Chirality | Racemic mixture |
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Idazoxan(INN) is adrugwhich is used inscientific research.It acts as both a selectiveα2adrenergic receptorantagonist,and an antagonist for theimidazoline receptor.[1][2][3][4]Idazoxan has been under investigation as anantidepressant,but it did not reach the market as such. More recently, it is under investigation as an adjunctive treatment inschizophrenia.Due to its α2receptor antagonism it is capable of enhancing therapeutic effects ofantipsychotics,possibly by enhancingdopamineneurotransmissionin theprefrontal cortexof the brain, a brain area thought to be involved in thepathogenesisof schizophrenia.
Alzheimer's research
[edit]Mice treated with idazoxan, which blocks theα2Areceptorwhich regulatesnorepinephrine,behaved similarly to control animals despite still having amyloid-beta plaques in the brain, as a proof-of-concept experiment that dramatically reducedAlzheimer'spathology and symptoms in two mouse models, potentially offering an immediate treatment for this devastating disease.[5]
Synthesis
[edit]Note that the literature method claims that the old original patented procedure gives a different reaction product formed through a rearrangement.
The reaction of catechol (1) with 2-Chloroacrylonitrile [920-37-6] (2) gives 2-cyano-1,4-benzodioxan [1008-92-0] (3).Pinner reactionwith alcoholic hydrogen chloride leads to the iminoether,[11](4). Treatment withethylenediamine[107-15-3] (5) gives the imidazoline ring affordingIdazoxin(6).
See also
[edit]References
[edit]- ^Bousquet P, Bruban V, Schann S, Greney H, Ehrhardt JD, Dontenwill M, Feldman J (June 1999). "Participation of imidazoline receptors and alpha(2-)-adrenoceptors in the central hypotensive effects of imidazoline-like drugs".Annals of the New York Academy of Sciences.881(1): 272–8.Bibcode:1999NYASA.881..272B.doi:10.1111/j.1749-6632.1999.tb09369.x.PMID10415925.S2CID38772290.
- ^Clarke RW, Harris J (2002)."RX 821002 as a tool for physiological investigation of alpha(2)-adrenoceptors".CNS Drug Reviews.8(2): 177–92.doi:10.1111/j.1527-3458.2002.tb00222.x.PMC6741674.PMID12177687.
- ^Yakubu MA, Hamilton CA, Howie CA, Reid JL (1988). "Idazoxan and brain alpha2-adrenoceptor in the rabbit".Brain Research.436:289–296.doi:10.1016/0006-8993(88)90402-7.PMID2848612.
- ^Hamilton CA, Yakubu MA, Jardine E, Reid JL (1991). "Imidazole binding sites in rabbit kidney and forebrain membranes".J Auton Pharmacol.11(4): 277–83.doi:10.1111/j.1474-8673.1991.tb00325.x.PMID1939285.
- ^Zhang F, Gannon M, Chen Y, Yan S, Zhang S, Feng W, et al. (January 2020)."β-amyloid redirects norepinephrine signaling to activate the pathogenic GSK3β/tau cascade".Science Translational Medicine.12(526).doi:10.1126/scitranslmed.aay6931.PMC7891768.PMID31941827.
- ^Chapleo CB, Myers PL (January 1981). "2-[2-(1, 4-benzodioxanyl)]-2-imidazoline hydrochloride".Tetrahedron Letters.22(48): 4839–4842.doi:10.1016/S0040-4039(01)92358-5.
- ^Chapleo CB, Davis JA, Myers PL, Readhead MJ, Stillings MR, Welbourn AP, Hampson FC, Sugden K (January 1984)."An investigation of some base induced transformations of the 1, 4‐benzodioxan ring system".Journal of Heterocyclic Chemistry.21(1): 77–80.doi:10.1002/jhet.5570210117.
- ^Chapleo CB, Myers PL, Butler RC, Doxey JC, Roach AG, Smith CF (June 1983). "alpha-adrenoreceptor reagents. 1. Synthesis of some 1,4-benzodioxans as selective presynaptic alpha 2-adrenoreceptor antagonists and potential antidepressants".Journal of Medicinal Chemistry.26(6): 823–31.doi:10.1021/jm00360a008.PMID6133953.
- ^US 2979511,Krapcho J, Lott WA, "Certain 1, 4-benzodioxanyl imidazolines and corresponding pyrimidines and process", issued 11 April 1961, assigned to Olin Corp.
- ^US 7338970,Bougaret J, Avan JL, Segonds R, "Pharmaceutical composition based on idazoxan, salts, hydrates or polymorphs thereof", issued 3 March 2008, assigned to Pierre Fabre Medicament.
- ^"2,3-Dihydro-1,4-benzodioxin-2-carbimidic acid ethyl ester".PubChem.U.S. National Library of Medicine. CID:10035919.
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