Gamfexine (WIN-1,344) is a centrally acting

stimulant Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...

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 ...

, which was tested as an adjunct treatment for withdrawn patients with

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

, but while effective for treating withdrawal it made psychotic symptoms worse. It was stated that gamfexine was the progenitor in the discovery of

venlafaxine Venlafaxine, sold under the brand name Effexor among others, is an antidepressant medication of the serotonin–norepinephrine reuptake inhibitor (SNRI) class. It is used to treat major depressive disorder, generalized anxiety disorder, pani ...

. This could be the reason why both agents share the same

suffix In linguistics, a suffix is an affix which is placed after the stem of a word. Common examples are case endings, which indicate the grammatical case of nouns and adjectives, and verb endings, which form the conjugation of verbs. Suffixes can ca ...

Synthesis

The precursor chemical is made from

benzyl cyanide Benzyl cyanide (abbreviated BnCN) is an organic compound with the chemical formula C6H5CH2CN. This colorless oily aromatic liquid is an important precursor to numerous compounds in organic chemistry. It is also an important pheromone in certain s ...

and

bromocyclohexane Bromocyclohexane (also called cyclohexyl bromide, abbreviated CXB) is an organic compound with the chemical formula . Uses and reactions It is used to match the refractive index of PMMA for example in confocal microscopy of colloids. A mixture ...

. This compound serves dual use in the synthesis of drofenine, hexasonium &

feclemine Feclemine (phenetamine) is a spasmolytic drug. Synthesis The chemical synthesis is discussed: Sodamide is used to alkylate cyclohexylphenylacetonitrile 893-23-0(1) (also used for drofenine) with 2-chloro-N,N,N',N'-tetraethylpropane-1,3-diam ...

. The synthesis of gamfexine has been discussed: Patents: The method discussed by Lednicer & Mitscher is slightly different from the patented procedure and uses 2-Cyclohexylidene-2-phenylacetonitrile 0461-98-0 This chemical is an odoriferous substance. It is known to have been used in the synthesis of Fenclexonium. Gamfexine synthesis

Alkylation of cyclohexylphenylacetonitrile 893-23-0(1) with 2-chloroethyldimethylamine (2), using NaNH2 as base, gives nitrile
PC412902
(3). Removal of the nitrile group apparently occurred upon reaction with more NaNH2. This completed the synthesis of ''Gamfexine'' (4). N.B. Note that the removal of cyanide also occurs in one of the syntheses of

chlorpheniramine Chlorphenamine (CP, CPM), also known as chlorpheniramine, is an antihistamine used to treat the symptoms of allergic conditions such as allergic rhinitis (hay fever). It is taken orally (by mouth). The medication takes effect within two hour ...

. Here though,

sulfuric acid Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid (English in the Commonwealth of Nations, Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen, ...

was used as the reagent for this step. An alternative synthesis strategy is envisioned to consist of Mannich reaction & organometallic addition to the carbonyl group (c.f.

trihexyphenidyl Trihexyphenidyl (THP, benzhexol, trihex, marketed as Artane and others) is an antispasmodic drug used to treat stiffness, tremors, spasms, and poor muscle control. It is an agent of the antimuscarinic class and is often used in management of P ...

), followed by reductive removal of the tertiary hydroxyl group; or by starting form Benzoylcyclohexane

12-50-5 1 (one, unit, unity) is a number, numeral, and glyph. It is the first and smallest positive integer of the infinite sequence of natural numbers. This fundamental property has led to its unique uses in other fields, ranging from science to sp ...

References

Stimulants Dimethylamino compounds {{nervous-system-drug-stub

Synthesis

See also

References