Manifaxine (developmental code name GW-320,659) is a norepinephrine–dopamine reuptake inhibitor developed by

GlaxoSmithKline GSK plc, formerly GlaxoSmithKline plc, is a British Multinational corporation, multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a Mergers and acquisitions, merger of Gl ...

through structural modification of radafaxine, an

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. ...

of hydroxybupropion and one of the

active metabolite An active metabolite is an active form of a drug after it has been processed by the body. Metabolites of drugs An active metabolite results when a drug is metabolized by the body into a modified form which continues to produce effects in the body ...

s of

bupropion Bupropion, sold under the brand names Wellbutrin and Zyban among others, is an atypical antidepressant primarily used to treat major depressive disorder and to support smoking cessation. It is also popular as an add-on medication in the cas ...

. Manifaxine was researched for treatment of

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by excessive amounts of inattention, hyperactivity, and impulsivity that are pervasive, impairing in multiple contexts, and otherwise age-inap ...

(ADHD) and

obesity Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's ...

and was found to be safe, reasonably effective, and well-tolerated for both applications. However, no results were reported following these initial trials and development was discontinued.

Synthesis

The Grignard reaction between 3,5-difluorobenzonitrile

4248-63-1 4 (four) is a number, numeral and digit. It is the natural number following 3 and preceding 5. It is the smallest semiprime and composite number, and is considered unlucky in many East Asian cultures. In mathematics Four is the smalles ...

(1) and ethylmangensium bromide gives 3,5-difluoropropiophenone

35306-45-5 __NOTOC__ Year 353 ( CCCLIII) was a common year starting on Friday (link will display the full calendar) of the Julian calendar. At the time, it was known as the Year of the Consulship of Magnentius and Decentius (or, less frequently, year 110 ...

(2). Halogenation with molecular bromine occurs at the alpha-keto position providing 2-bromo-3',5'-difluoropropiophenone

35306-46-6 __NOTOC__ Year 353 ( CCCLIII) was a common year starting on Friday (link will display the full calendar) of the Julian calendar. At the time, it was known as the Year of the Consulship of Magnentius and Decentius (or, less frequently, year 110 ...

(3). Intermolecular ring formation with DL-Alaninol (2-Aminopropanol) 168-72-5completed the synthesis of Manifaxine (4).

References

Fluoroarenes GSK plc brands Substituted amphetamines Phenylmorpholines Norepinephrine–dopamine reuptake inhibitors Stimulants Tertiary alcohols {{Nervous-system-drug-stub

Synthesis

See also

References