Abstract
A series of quinoline/naphthalene-difluoromethylphosphonates were prepared and were found to be potent PTP1B inhibitors. Most of these compounds bearing polar functionalities or large lipophilic residues did not show appreciable oral bioavailability in rodents while small and less polar analogs displayed moderate to good oral bioavailability. The title compound was found to have the best overall potency and pharmacokinetic profile and was found to be efficacious in animal models of diabetes and cancer.
MeSH terms
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Animals
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Combinatorial Chemistry Techniques
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Diabetes Mellitus / chemically induced
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Disease Models, Animal
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Drug Design
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Drug Screening Assays, Antitumor
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Haplorhini
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Hydrocarbons, Halogenated / chemical synthesis*
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Hydrocarbons, Halogenated / chemistry
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Hydrocarbons, Halogenated / pharmacology*
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Mice
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Molecular Structure
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Naphthalenes / chemical synthesis*
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Naphthalenes / chemistry
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Naphthalenes / pharmacology*
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Neoplasms / chemically induced
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Organophosphonates / chemical synthesis*
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Organophosphonates / chemistry
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Organophosphonates / pharmacology*
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Protein Tyrosine Phosphatase, Non-Receptor Type 1 / antagonists & inhibitors*
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Rats
Substances
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((3-bromo-7-cyano-2-naphthyl)(difluoro)methyl)phosphonic acid
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Hydrocarbons, Halogenated
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Naphthalenes
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Organophosphonates
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Protein Tyrosine Phosphatase, Non-Receptor Type 1