Abstract
Structural modification and cellular adhesion inhibition activities of pyridazinone-substituted phenylalanine amide alpha(4) integrin antagonists are described. Functionality requirements for the arylamide moiety and the carboxylic acid group were demonstrated. The study also revealed novel structure-activity relationships (SAR) for arylated pyridazinones. A correlation between bioavailability and permeability was also explored. A selected compound showed effectiveness in a mouse leukocytosis study.
MeSH terms
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Amides / chemical synthesis
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Amides / chemistry*
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Amides / pharmacokinetics
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Amides / pharmacology*
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Animals
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Biological Availability
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Caco-2 Cells
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Cell Adhesion / drug effects
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Humans
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Integrin alpha4 / chemistry
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Integrin alpha4 / metabolism*
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Intestinal Absorption
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Leukocytosis / drug therapy
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Mice
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Phenylalanine / analogs & derivatives*
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Phenylalanine / chemical synthesis
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Phenylalanine / pharmacokinetics
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Phenylalanine / pharmacology
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Pyridazines / chemical synthesis
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Pyridazines / chemistry*
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Pyridazines / pharmacokinetics
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Pyridazines / pharmacology*
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Rats
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Structure-Activity Relationship
Substances
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Amides
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Pyridazines
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Integrin alpha4
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Phenylalanine