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.
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.
D000818:Animals; D001561:Benzilates / Q000037:antagonists & inhibitors / Q000737:chemistry; D001667:Binding, Competitive; D016466:CHO Cells; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007035:Hypothermia / Q000139:chemically induced; D008297:Male; D051379:Mice; D008958:Models, Molecular; D018721:Muscarinic Agonists / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D009422:Nervous System Diseases / Q000188:drug therapy*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D020318:Rats, Long-Evans; D011976:Receptors, Muscarinic / Q000378:metabolism; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
D001561:Benzilates; D018721:Muscarinic Agonists; D011725:Pyridines; D011976:Receptors, Muscarinic; D013830:Thiadiazoles; D005576:Colforsin; D002217:Carbachol; D000242:Cyclic AMP