efaroxan
{{Short description|Chemical compound}}
{{Drugbox
| verifiedrevid = 437176178
| IUPAC_name = 2-(2-ethyl-2,3-dihydro-1-benzofuran-2-yl)-4,5-dihydro-1H-imidazole
| image = Efaroxan.png
| tradename =
| pregnancy_category =
| legal_status = Uncontrolled
| routes_of_administration = Oral
| bioavailability =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 89197-32-0
| ATC_prefix = none
| ATC_suffix =
| PubChem = 72016
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 65015
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = G00490L21H
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 57895
| C=13 | H=16 | N=2 | O=1
| smiles = N\1=C(\NCC/1)C3(Oc2ccccc2C3)CC
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C13H16N2O/c1-2-13(12-14-7-8-15-12)9-10-5-3-4-6-11(10)16-13/h3-6H,2,7-9H2,1H3,(H,14,15)
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = RATZLMXRALDSJW-UHFFFAOYSA-N
}}
Efaroxan is an α2-adrenergic receptor antagonist{{cite journal |vauthors=Chopin P, Colpaert FC, Marien M |title=Effects of alpha-2 adrenoceptor agonists and antagonists on circling behavior in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal pathway |journal=J. Pharmacol. Exp. Ther. |volume=288 |issue=2 |pages=798–804 |date=February 1999 |doi=10.1016/S0022-3565(24)38022-X |pmid=9918591 |url=http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=9918591}} and antagonist of the imidazoline receptor.
Synthesis
[[File:Efaroxan synthesis.svg|thumb|center|500px|Synthesis (Cmp#13):Chapleo, Christopher B.; Myers, Peter L.; Butler, Richard C. M.; Davis, John A.; Doxey, John C.; Higgins, Stanley D.; Myers, Malcolm; Roach, Alan G.; Smith, Colin F. C. (1984). ".alpha.-Adrenoceptor reagents. 2. Effects of modification of the 1,4-benzodioxan ring system on .alpha.-adrenoreceptor activity". Journal of Medicinal Chemistry 27 (5): 570–576. doi:10.1021/jm00371a003. Revised:Mayer, P.; Brunel, P.; Imbert, T. (1999). "A new efficient synthesis of efaroxan". Bioorganic & Medicinal Chemistry Letters 9 (20): 3021–3022. doi:10.1016/S0960-894X(99)00531-4. Couture, K.; Gouverneur, V.; Mioskowski, C. (1999). "A new approach to the synthesis of efaroxan". Bioorganic & Medicinal Chemistry Letters 9 (20): 3023–3026.
doi:10.1016/S0960-894X(99)00530-2.
]]
The Darzens reaction between 2-fluorobenzaldehyde [57848-46-1] (1) and Ethyl 2-bromobutyrate [533-68-6] (2) gives ethyl 2-ethyl-3-(2-fluorophenyl)oxirane-2-carboxylate, [https://pubchem.ncbi.nlm.nih.gov/compound/100942311 CID:100942311] (3). A catalytic hydrogenation over Pd/C would give ethyl 2-[(2-fluorophenyl)methyl]-2-hydroxybutanoate, [https://pubchem.ncbi.nlm.nih.gov/compound/77591056 CID:77591056] (4). Saponification of the ester then gives 2-[(2-Fluorophenyl)methyl]-2-hydroxybutanoic acid, [https://pubchem.ncbi.nlm.nih.gov/compound/53869347 CID:53869347] (5). Treatment with 2 molar equivalents of sodium hydride apparently gives 2-Ethyl-2,3-dihydrobenzofuran-2-carboxylic acid [111080-50-3] (6). Treatment of the carboxylic acid with thionyl chloride then gives the acid chloride and subsequent treatment of this with ethylenediamine in the presence of trimethylaluminium completed the synthesis of {{Highlight|Efaroxan}} (8).
See also
References
{{Reflist|2}}
External links
- {{Commonscatinline}}
{{Adrenergics}}
{{Imidazolinergics}}
Category:Imidazoline receptor modulators
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