Abstract:
INTRODUCTION:Bitopic M ligands, that is, ligands that interact both with the ortho- and allosteric binding sites of the M receptor subtypes, hold great potential as novel selective for muscarinic acetylcholine (M) ligands for several therapeutic applications. Areas covered: The patent application describes a set of compounds based on the neurotransmitter acetylcholine applying the Schulman-model for M ligands comprising heterocyclic (often quaternary) amines and a benzene ring (often as benzoic acid esters) to act as bitopic ligands. The compounds claimed hold functional selectivity and are supposed to be therapeutically applied as neuromuscular blocking agents, in asthma as well as CNS diseases. In vitro evaluations of selected compounds supported bitopic binding and some degree of functional selectivity was observed - albeit no selectivity was observed in binding studies. Expert opinion: The quaternary amine structure of the compounds claimed will prohibit penetration into the CNS and their ester structure will lead to significant metabolic instability which will hamper therapeutic applications for many indications. Furthermore, high affinity and subtype selectivity with regard to binding affinity which is observed for bitopic and allosteric ligands in the current literature is not observed for the compounds described in the patent.
journal_name
Expert Opin Ther Patjournal_title
Expert opinion on therapeutic patentsauthors
Holzgrabe U,Decker Mdoi
10.1080/13543776.2017.1272577subject
Has Abstractpub_date
2017-02-01 00:00:00pages
121-125issue
2eissn
1354-3776issn
1744-7674journal_volume
27pub_type
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journal_title:Expert opinion on therapeutic patents
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journal_title:Expert opinion on therapeutic patents
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journal_title:Expert opinion on therapeutic patents
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journal_title:Expert opinion on therapeutic patents
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