Manifaxine Explained

Manifaxine (developmental code name GW-320,659) is a norepinephrine–dopamine reuptake inhibitor developed by GlaxoSmithKline through structural modification of radafaxine, an isomer of hydroxybupropion and one of the active metabolites of bupropion.^[1] Manifaxine was researched for treatment of attention deficit hyperactivity disorder (ADHD) and obesity and was found to be safe, reasonably effective, and well-tolerated for both applications.^{[2] [3]} However, no results were reported following these initial trials and development was discontinued.

Synthesis

The Grignard reaction between 3,5-difluorobenzonitrile [64248-63-1] (1) and ethylmagnesium bromide gives 3,5-difluoropropiophenone [135306-45-5] (2). Halogenation with molecular bromine occurs at the alpha-keto position providing 2-bromo-3',5'-difluoropropiophenone [135306-46-6] (3). Intermolecular ring formation with DL-Alaninol (2-Aminopropanol) [6168-72-5] completed the synthesis of Manifaxine (4).

See also

• 3,5-Difluoromethcathinone
• 3-Fluorophenmetrazine

Notes and References

1. Web site: Manifaxine - AdisInsight.
2. DeVeaugh-Geiss J, Conners CK, Sarkis EH, Winner PK, Ginsberg LD, Hemphill JM, Laurenza A, Barrows CE, Webster CJ, Stotka CJ, Asgharnejad M . 6 . GW320659 for the treatment of attention-deficit/hyperactivity disorder in children . Journal of the American Academy of Child and Adolescent Psychiatry . 41 . 8 . 914–20 . August 2002 . 10.1097/00004583-200208000-00009 . 12162627 .
3. Spraggs CF, Pillai SG, Dow D, Douglas C, McCarthy L, Manasco PK, Stubbins M, Roses AD . 6 . Pharmacogenetics and obesity: common gene variants influence weight loss response of the norepinephrine/dopamine transporter inhibitor GW320659 in obese subjects . Pharmacogenetics and Genomics . 15 . 12 . 883–9 . December 2005 . 10.1097/01213011-200512000-00006 . 16272960 . 40809351 .