Synthesis and SAR of pyridazinone-substituted phenylalanine amide α4 integrin antagonists

Structural modification and cellular adhesion inhibition activities of pyridazinone-substituted phenylalanine amide α4 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.

Structure–activity relationships (SAR) within a series of pyridazinone-functionalized phenylalanine amide α4 integrin antagonists are described.Figure optionsDownload as PowerPoint slide