Abstract
Two novel series of 5-nitro-2-phenoxybenzoic acid derivatives are designed as potent PAI-1 inhibitors using hybridization and conformational restriction strategy in the tiplaxtinin and piperazine chemo types. The lead compounds 5a, 6c, and 6e exhibited potent PAI-1 inhibitory activity and favorable oral bioavailability in the rodents.
Copyright © 2011 Elsevier Ltd. All rights reserved.
MeSH terms
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Administration, Oral
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Animals
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Benzoates / chemistry*
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Benzoates / pharmacokinetics
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Benzoates / pharmacology*
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Biological Availability
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Disease Models, Animal
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Drug Design*
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Drug Discovery*
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Drug Evaluation, Preclinical
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Indoleacetic Acids / chemistry
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Indoleacetic Acids / pharmacology
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Male
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Molecular Structure
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Phenyl Ethers / chemistry*
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Phenyl Ethers / pharmacokinetics
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Phenyl Ethers / pharmacology
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Piperazine
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Piperazines / chemistry
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Plasminogen Activator Inhibitor 1 / metabolism*
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Rats
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Rats, Wistar
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Structure-Activity Relationship
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Thrombosis / chemically induced
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Thrombosis / drug therapy
Substances
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Benzoates
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Indoleacetic Acids
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Phenyl Ethers
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Piperazines
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Plasminogen Activator Inhibitor 1
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tiplaxtinin
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Piperazine