Tazomeline (LY-287,041) is a

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

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-rece ...

agonist An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...

. 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, dietar ...

s for the treatment of cognitive dysfunction such as that seen in

Alzheimer's disease Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...

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 withdra ...

, 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 Potassium cyanide is a compound with the formula KCN. This colorless crystalline salt, similar in appearance to sugar, is highly soluble in water. Most KCN is used in gold mining, organic synthesis, and electroplating. Smaller applications includ ...

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 Iodomethane, also called methyl iodide, and commonly abbreviated "MeI", is the chemical compound with the formula CH3I. It is a dense, colorless, volatile liquid. In terms of chemical structure, it is related to methane by replacement of one h ...

gives 3-(4-hexylthio-1,2,5-thiadiazol-3-yl)-1-methylpyridinium iodide
CID:19075299
(6). The reduction of the pyridine with sodium borohydride 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