Vedaclidine (

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 accommo ...

, codenamed LY-297,802, NNC 11-1053) is an experimental analgesic drug which acts as a mixed agonist–antagonist at

muscarinic acetylcholine receptors 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 ...

, being a potent and selective agonist for the M₁ and M₄ subtypes, yet an antagonist at the M₂, M₃ and M₅ subtypes. It is orally active and an effective analgesic over 3× the potency of

morphine Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a pain medication, and is also commonly used recreationally, or to make other illicit opioids. T ...

, with side effects such as salivation and tremor only occurring at many times the effective analgesic dose. Human trials showed little potential for development of dependence or abuse, and research is continuing into possible clinical application in the treatment of

neuropathic pain Neuropathic pain is pain caused by damage or disease affecting the somatosensory system. Neuropathic pain may be associated with abnormal sensations called dysesthesia or pain from normally non-painful stimuli (allodynia). It may have continuous ...

and

cancer pain Pain in cancer may arise from a tumor compressing or infiltrating nearby body parts; from treatments and diagnostic procedures; or from skin, nerve and other changes caused by a hormone imbalance or immune response. Most chronic (long-lasting) pa ...

relief.

Synthesis

: The

Knoevenagel condensation In organic chemistry, the Knoevenagel condensation () reaction is a type of chemical reaction named after German chemist Emil Knoevenagel. It is a modification of the aldol condensation. A Knoevenagel condensation is a nucleophilic addition o ...

between 3-Quinuclidone 731-38-2(1) & ethyl cyanoacetate 05-56-6(2) gives Ethyl (1-azabicyclo .2.2ctan-3-ylidine)cyanoacetate
CID:54445383
(3). The

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 ...

of the olefin group gave Ethyl (1-azabicyclo .2.2ctan-3-yl)cyanoacetate 41593-50-2(4). The reaction with sodium in ethanol, followed by addition of isoamylnitrite 10-46-3led to (1-Azabicyclo .2.2ctan-3-yl)hydroxyiminoacetonitrile
CID:73192825
(5). Halogenation with Disulfur dichloride 0025-67-9in DMF gave 3-(3-Chloroquinuclidine-3-yl)-4-chloro-1,2,5-thiadiazole
CID:9795252
(6). :

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 ...

went on to give 3-Chloro-4-quinuclidin-3-yl-1,2,5-thiadiazole
CID:9942707
(7). : The reaction with sodium hydrogen sulfide in the presence of potassium carbonate, followed by addition of

1-bromobutane 1-Bromobutane is the organobromine compound with the formula CH3(CH2)3Br. It is a colorless liquid, although impure samples appear yellowish. It is insoluble in water, but soluble in organic solvents. It is a primarily used as a source of the buty ...

completed the synthesis of ''Vedaclidine'' (8).

References

{{Muscarinic acetylcholine receptor modulators Analgesics Muscarinic agonists Muscarinic antagonists Quinuclidines Thiadiazoles Thioethers Experimental drugs Butyl compounds

Synthesis

See also

References