Manifaxine

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.^[1]

Manifaxine

Clinical data
Other names	GW-320,659
Routes of administration	Oral
ATC code	none
Identifiers
IUPAC name (2S,3S,5R)-2-(3,5-difluorophenyl)-3,5-dimethylmorpholin-2-ol
CAS Number	135306-39-7 Y
PubChem CID	60829
ChemSpider	54816 N
UNII	J8IE53G2IV
CompTox Dashboard (EPA)	DTXSID60928953
Chemical and physical data
Formula	C12H15F2NO2
Molar mass	243.254 g·mol−1
3D model (JSmol)	Interactive image
SMILES C[C@@H]1CO[C@]([C@@H](N1)C)(C2=CC(=CC(=C2)F)F)O
InChI InChI=1S/C12H15F2NO2/c1-7-6-17-12(16,8(2)15-7)9-3-10(13)5-11(14)4-9/h3-5,7-8,15-16H,6H2,1-2H3/t7-,8+,12-/m1/s1 N Key:OZGPVYJHWWPEFT-RGNHYFCHSA-N N
NY (what is this?)  (verify)

Synthesis

Synthesis:^[4] Patent:^[5] See also:^[6][7]

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