Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders.

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Cao Y, Zhang M, Wu C, Lee S, Wroblewski ME, Whipple T, Nagy PI, Takacs-Novak K, Balazs A, Toros S, Messer WS Jr

Synthesis and biological characterization of 1-methyl-1,2,5,6-tetrahydropyridyl-1,2,5-thiadiazole derivatives as muscarinic agonists for the treatment of neurological disorders.

J Med Chem. 2003 Sep 25;46(20):4273-86.

PubMed ID

13678406 [ View in PubMed

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Abstract

Muscarinic agonists might be useful in the treatment of neurological disorders, including Alzheimer's disease, schizophrenia, chronic pain, and drug abuse. Previous studies identified a series of bis-1,2,5-thiadiazole derivatives of 1,2,5,6-tetrahydropyridine with high activity and selectivity for muscarinic receptors. To develop compounds with improved central nervous system penetration, several new derivatives were synthesized and characterized for muscarinic receptor binding and activity. One ligand (11) exhibited agonist activity at M(1), M(2), and M(4) receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Carbamoylcholine	Muscarinic acetylcholine receptor M2	IC 50 (nM)	13	N/A	N/A	Details
Carbamoylcholine	Muscarinic acetylcholine receptor M4	IC 50 (nM)	1000	N/A	N/A	Details