Tazomeline (LY-287,041) is a drug which acts as a non- selective

muscarinic acetylcholine receptor Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rec ...

agonist. It was in

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, diet ...

s for the treatment of

cognitive dysfunction Cognitive disorders (CDs), also known as neurocognitive disorders (NCDs), are a category of mental health disorders that primarily affect cognitive abilities including learning, memory, perception, and problem solving. Neurocognitive disorders i ...

such as that seen in Alzheimer's disease and

schizophrenia Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social wit ...

, but development was apparently scrapped for unknown reasons. Another of the patented uses is for the treatment of "severe painful conditions".

Synthesis

: A Strecker type alpha-amino nitrile between nicotinaldehyde, potassium cyanide and ammonium chloride gives amino(pyridin-3-yl)acetonitrile 31988-63-1(2). The halogenation of this intermediate with

sulfur monochloride Disulfur dichloride is the inorganic compound of sulfur and chlorine with the formula S2Cl2. Some alternative names for this compound are ''sulfur monochloride'' (the name implied by its empirical formula, SCl), ''disulphur dichloride'' (British ...

0025-67-9in DMF led to 3-chloro-4-(3-pyridyl)-1,2,5-thiadiazole 31986-28-2(3). : Thioether formation with 1-Hexanethiol 11-31-9(4) in the presence of

sodium hydrogen sulfide Sodium hydrosulfide is the chemical compound with the formula NaHS. This compound is the product of the half-neutralization of hydrogen sulfide () with sodium hydroxide (NaOH). NaSH and sodium sulfide are used industrially, often for similar purpos ...

, DMF and K2CO3 gave 3-(4-hexylthio-1,2,5-thiadiazol-3-yl)pyridine
CID:10755149
(5). Alkylation with methyl iodide gives 3-(4-hexylthio-1,2,5-thiadiazol-3-yl)-1-methylpyridinium iodide
CID:19075299
(6). The reduction of the pyridine with

sodium borohydride Sodium borohydride, also known as sodium tetrahydridoborate and sodium tetrahydroborate, is an inorganic compound with the formula Na BH4. This white solid, usually encountered as an aqueous basic solution, is a reducing agent that finds applica ...

in alcohol gives the tetrahydropyridine and hence completed the synthesis of Tazomeline (7).

References

{{Muscarinic acetylcholine receptor modulators Muscarinic agonists Tetrahydropyridines Thiadiazoles

Synthesis

See also

References