Flumexadol (

INN Inns are generally establishments or buildings where travelers can seek lodging, and usually, food and drink. Inns are typically located in the country or along a highway. Before the advent of motorized transportation, they also provided accomm ...

; developmental codes CERM-1841 and 1841-CERM) is a

drug A drug is any chemical substance other than a nutrient or an essential dietary ingredient, which, when administered to a living organism, produces a biological effect. Consumption of drugs can be via insufflation (medicine), inhalation, drug i ...

described and researched as a non-

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

analgesic An analgesic drug, also called simply an analgesic, antalgic, pain reliever, or painkiller, is any member of the group of drugs used for pain management. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in s ...

which was never marketed. It has been found to act as an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the

serotonin Serotonin (), also known as 5-hydroxytryptamine (5-HT), is a monoamine neurotransmitter with a wide range of functions in both the central nervous system (CNS) and also peripheral tissues. It is involved in mood, cognition, reward, learning, ...

5-HT_1A (pK_i = 7.1) and 5-HT_2C (pK_i = 7.5)

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

s and, to a much lesser extent, of the 5-HT_2A (pK_i = 6.0) receptor. According to Nilsson (2006) in a paper on 5-HT_2C receptor agonists as potential

anorectic An anorectic is a drug that reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desi ...

s, "The (+)-enantiomer of this compound showed ..affinity for the 5-HT_2C receptor (K_i) 25 nM) ..and was 40-fold selective over the 5-HT_2A receptor in receptor binding studies. The racemic version .. also known as 1841 CERM, was originally reported to possess analgesic properties while no association with 5-HT_2C receptor activity was mentioned." It is implied that flumexadol might be employable as an anorectic in addition to analgesic. Though flumexadol itself has never been approved for medical use, oxaflozane (brand name Conflictan) is a

prodrug A prodrug is a pharmacologically inactive medication or compound that, after intake, is metabolized (i.e., converted within the body) into a pharmacologically active drug. Instead of administering a drug directly, a corresponding prodrug can be ...

of the compound that was formerly used clinically in

France France, officially the French Republic, is a country located primarily in Western Europe. Overseas France, Its overseas regions and territories include French Guiana in South America, Saint Pierre and Miquelon in the Atlantic Ocean#North Atlan ...

as an

antidepressant Antidepressants are a class of medications used to treat major depressive disorder, anxiety disorders, chronic pain, and addiction. Common side effects of antidepressants include Xerostomia, dry mouth, weight gain, dizziness, headaches, akathi ...

and

anxiolytic An anxiolytic (; also antipanic or anti-anxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxie ...

agent.

Synthesis

Halogenation of 2-chloroethyl vinyl ether (1) with molecular bromine gives 1,2-dibromo-1-(2-chloroethoxy)ethane (2).

Grignard reaction The Grignard reaction () is an organometallic chemical reaction in which, according to the classical definition, carbon alkyl, allyl, vinyl, or aryl magnesium halides (Grignard reagent) are added to the carbonyl groups of either an aldehyde or ...

with 3-bromobenzotrifluoride (3) gives 1- -bromo-1-(2-chloroethoxy)ethyl3-(trifluoromethyl)benzene (4). Treatment with benzylamine gives 4-benzyl-2- -(trifluoromethyl) phenylorpholine (5).

Catalytic hydrogenation Hydrogenation is a chemical reaction between molecular hydrogen (H2) and another compound or element, usually in the presence of a catalyst such as nickel, palladium or platinum. The process is commonly employed to reduce or saturate organic ...

strips the benzyl

protecting group A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis. In man ...

completing the synthesis of flumexadol (6).

References

{{Serotonergics 5-HT1A agonists 5-HT2A agonists 5-HT2C agonists Analgesics Anorectics Antidepressants Anxiolytics Phenylmorpholines Trifluoromethyl compounds

Synthesis

See also

References