Lomevactone
{{short description|Chemical compound}}
{{Drugbox
| IUPAC_name = 4-(4-Chlorophenyl)-6-methyl-3-phenyltetrahydro-2H-pyran-2-one
| image = Lomevactone.png
| tradename =
| pregnancy_category =
| legal_status =
| routes_of_administration =
| bioavailability =
| metabolism =
| elimination_half-life =
| excretion =
| CAS_number = 81478-25-3
| CAS_supplemental =
(3R,4R,6R): 82510-81-4
rel-(3R,4R,6R): 75115-73-0
| ATC_prefix = None
| ATC_suffix =
| PubChem = 100079
| ChemSpiderID = 90435
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = TP71SPS85C
| C=18 | H=17 | Cl=1 | O=2
| smiles = Clc1ccc(cc1)C2C(C(=O)OC(C)C2)c3ccccc3
}}
Lomevactone (INN; developmental code name DR-250) is a drug described as a psychostimulant and antidepressant which was synthesized and assayed in the 1980s, but was never marketed.{{cite book | author = David J. Triggle | title = Dictionary of pharmacological agents | publisher = Chapman & Hall | location = London | year = 1997 | isbn = 0-412-46630-9 | url = https://books.google.com/books?id=A0THacd46ZsC&q=lomevactone&pg=PA1231}}{{cite journal |vauthors=Poncelet M, Chermat R, Soubrie P, Simon P | title = The progressive ratio schedule as a model for studying the psychomotor stimulant activity of drugs in the rat | journal = Psychopharmacology | volume = 80 | issue = 2 | pages = 184–9 | year = 1983 | pmid = 6136063 | doi = 10.1007/BF00427967| s2cid = 2372145 }}
Stereoisomers
There are eight possible stereoisomers of lomevactone. It is the (3R,4R,6R)-form that has the psychotherapeutic properties.Axiotis, S.; Druex, J.; Perrin, M.; Royer, J. (1982). "Conformations in the tetrahydropyran-2-one ring". Tetrahedron. 38 (4): 499–504. doi:10.1016/0040-4020(82)80093-8.{{cite journal | vauthors=((Axiotis, S.)), ((Sollier, J.-C.)), ((Dreux, J.)), ((Chermat, R.)), ((Poncelet, M.)), ((Simon, P.)) | journal=European Journal of Medicinal Chemistry | title=Tétrahydropyrones-2 III. Recherche d'une activité psychostimulante spécifique | volume=22 | issue=4 | pages=293–303 | date= July 1987 | doi=10.1016/0223-5234(87)90266-2}}
:File:Lomevactone.svg{{clear-left}}
Synthesis
The conjugate 1,4-alkylation reaction between 4-chlorobenzylideneacetone (1) and phenylacetonitrile (2) gives 3-(4-chlorophenyl)-5-oxo-2-phenylhexanenitrile (3). The selective reduction of the keto group to the alcohol with sodium borohydride gives 3-(4-chlorophenyl)-5-hydroxy-2-phenylhexanenitrile (4). Hydrolysis of the nitrile to an acid gives 3-(4-chlorophenyl)-5-hydroxy-2-phenylhexanoic acid. This is followed by lactone formation completing the synthesis of lomevactone (5).
References
{{Reflist}}
{{Antidepressants}}
{{Stimulants}}
Category:4-Chlorophenyl compounds
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