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

Yang Cao; Minjia Zhang; Cindy Wu; Selina Lee; Mary Elizabeth Wroblewski; Trisha Whipple; Peter I. Nagy; Krisztina Takács-Novák; Attila Balázs; Szilárd Torös; William S. Messer

doi:10.1021/jm0301235

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

Yang Cao, Minjia Zhang, Cindy Wu, Selina Lee, Mary Elizabeth Wroblewski, Trisha Whipple, Peter I. Nagy, Krisztina Takács-Novák, Attila Balázs, Szilárd Torös, William S. Messer

Research output: Contribution to journal › Article › peer-review

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 M₁, M₂, and M₄ receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.

Original language	English (US)
Pages (from-to)	4273-4286
Number of pages	14
Journal	Journal of medicinal chemistry
Volume	46
Issue number	20
DOIs	https://doi.org/10.1021/jm0301235
State	Published - Sep 25 2003
Externally published	Yes

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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Cao, Y., Zhang, M., Wu, C., Lee, S., Wroblewski, M. E., Whipple, T., Nagy, P. I., Takács-Novák, K., Balázs, A., Torös, S., & Messer, W. S. (2003). 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. Journal of medicinal chemistry, 46(20), 4273-4286. https://doi.org/10.1021/jm0301235

Cao, Y, Zhang, M, Wu, C, Lee, S, Wroblewski, ME, Whipple, T, Nagy, PI, Takács-Novák, K, Balázs, A, Torös, S & Messer, WS 2003, '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', Journal of medicinal chemistry, vol. 46, no. 20, pp. 4273-4286. https://doi.org/10.1021/jm0301235

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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 M1, M2, and M4 receptors, a selectivity profile suggesting potential utility in the treatment of schizophrenia.",

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AU - Wu, Cindy

AU - Lee, Selina

AU - Wroblewski, Mary Elizabeth

AU - Whipple, Trisha

AU - Nagy, Peter I.

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AU - Torös, Szilárd

AU - Messer, William S.

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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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