Lomevactone

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.[1][2]

Lomevactone
Clinical data
ATC code
  • None
Identifiers
  • 4-(4-Chlorophenyl)-6-methyl-3-phenyltetrahydro-2H-pyran-2-one
CAS Number
  • 81478-25-3
    (3R,4R,6R): 82510-81-4
    rel-(3R,4R,6R): 75115-73-0
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC18H17ClO2
Molar mass300.78 g·mol−1
3D model (JSmol)
  • Clc1ccc(cc1)C2C(C(=O)OC(C)C2)c3ccccc3

Stereoisomers

There are eight possible stereoisomers of lomevactone. It is the (3R,4R,6R)-form that has the psychotherapeutic properties.[3][4]

(3R,4R,6R)-Lomevactone

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).

Synthesis:[5] Patents:[6][7]

References
  1. David J. Triggle (1997). Dictionary of pharmacological agents. London: Chapman & Hall. ISBN 0-412-46630-9.
  2. Poncelet M, Chermat R, Soubrie P, Simon P (1983). "The progressive ratio schedule as a model for studying the psychomotor stimulant activity of drugs in the rat". Psychopharmacology. 80 (2): 184–9. doi:10.1007/BF00427967. PMID 6136063. S2CID 2372145.
  3. 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.
  4. Axiotis, S., Sollier, J.-C., Dreux, J., Chermat, R., Poncelet, M., Simon, P. (July 1987). "Tétrahydropyrones-2 III. Recherche d'une activité psychostimulante spécifique". European Journal of Medicinal Chemistry. 22 (4): 293–303. doi:10.1016/0223-5234(87)90266-2.
  5. Axiotis, S. et al, Eur. J. Med. Chem.-Chim. Ther., 1981, 16, 431, 439.
  6. Pierre Simon & Jacques Dreux, U.S. Patent 4,287,206 (1981 to Sanofi Aventis France).
  7. 시몽 삐에르 & 드로 짝끄, KR830002288 (1983).
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