Abstract
A quaternary ammonium betaine 7 is described which shows exceptional potency and selectivity (1.4 to >3 logs) for the αvβ6 integrin receptor over the other αv integrins as determined in cell adhesion assays. 7 is prepared by remarkably stereoselective methylation, the origins of which are discussed. The chemical, biological, physicochemical, and pharmacokinetic properties of 7 and its docking into αvβ6 are described along with related analogues.
MeSH terms
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Animals
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Antigens, Neoplasm / chemistry
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Antigens, Neoplasm / metabolism
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Betaine / chemistry
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Betaine / pharmacokinetics
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Betaine / pharmacology*
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Cells, Cultured
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Crystallography, X-Ray
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Hepatocytes / cytology
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Hepatocytes / drug effects
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Hepatocytes / metabolism
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Humans
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Integrins / antagonists & inhibitors*
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Integrins / chemistry
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Integrins / metabolism
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Methylation
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Models, Chemical
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Molecular Docking Simulation
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Molecular Structure
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Protein Binding
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Protein Conformation
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Pyrrolidines / chemistry*
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Quaternary Ammonium Compounds / chemistry
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Quaternary Ammonium Compounds / pharmacokinetics
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Quaternary Ammonium Compounds / pharmacology*
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Rats
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Stereoisomerism
Substances
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Antigens, Neoplasm
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Integrins
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Pyrrolidines
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Quaternary Ammonium Compounds
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integrin alphavbeta6
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Betaine
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pyrrolidine