104315-75-5Relevant academic research and scientific papers
Synthesis of novel and functionally selective non-competitive muscarinic antagonists as chemical probes
Boulos, John F.,Jakubik, Jan,Boulos, John M.,Randakova, Alena,Momirov, Jelena
, p. 93 - 104 (2017/10/06)
Muscarinic receptors are known to play important biological roles and are drug targets for several human diseases. In a pilot study, novel muscarinic antagonists were synthesized and used as chemical probes to obtain additional information of the muscarinic pharmacophore. The design of these ligands made use of current orthosteric and allosteric models of drug–receptor interactions together with chemical motifs known to achieve muscarinic receptor selectivity. This approach has led to the discovery of several non-competitive muscarinic ligands that strongly bind at a secondary receptor site. These compounds were found to be non-competitive antagonists that completely abolished carbachol activation in functional assays. Several of these compounds antagonized functional response to carbachol with great potency at M1 and M4 than at the rest of receptor subtypes.
BITOPIC MUSCARINIC AGONISTS AND ANTAGONISTS AND METHODS OF SYNTHESIS AND USE THEREOF
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, (2014/02/15)
Compositions for treating a condition associated with activity of a muscarinic receptor (e.g., one or more of M1, M2, M3, M4, M5) and for anesthetizing a subject include a bitopic muscarinic antagonist or agonist. A bitopic muscarinic antagonist named JB-D4 was discovered. This bitopic ligand and its structural analogs, as well as bitopic muscarinic agonists, may be used as neuromuscular blocking agents (e.g., for use in compositions for anesthetizing a subject) and for the treatment of central nervous system disorders (e.g., Parkinson's disease, Schizophrenia, etc.), Overactive Bladder Syndrome, Chronic Obstructive Pulmonary Disease, asthma, and many other diseases associated with the activation or inhibition of M1-M5 acetylcholine receptors.
