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.

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.
Authors	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 Jr
Journal	Journal of medicinal chemistry (J Med Chem) Vol. 46 Issue 20 Pg. 4273-86 (Sep 25 2003) ISSN: 0022-2623 [Print] United States
PMID	13678406 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Benzilates Muscarinic Agonists Pyridines Receptors, Muscarinic Thiadiazoles Colforsin Carbachol Cyclic AMP
Topics	Animals Benzilates (antagonists & inhibitors, chemistry) Binding, Competitive CHO Cells Carbachol (pharmacology) Cell Line Colforsin (antagonists & inhibitors, pharmacology) Cricetinae Cyclic AMP (metabolism) Humans Hypothermia (chemically induced) Male Mice Models, Molecular Muscarinic Agonists (chemical synthesis, metabolism, pharmacology) Nervous System Diseases (drug therapy) Pyridines (chemical synthesis, chemistry, metabolism, pharmacology) Radioligand Assay Rats Rats, Long-Evans Receptors, Muscarinic (metabolism) Thiadiazoles (chemical synthesis, chemistry, metabolism, pharmacology)

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