4-(Pyrrolidinyl)methoxybenzoic acid derivatives as a potent, orally active VLA-4 antagonist

Article abstract of DOI:10.1248/cpb.54.1515

A novel series of benzoic acid derivatives as VLA-4 antagonists were synthesized. Optimization, focusing on activity and lipophilicity needed for cell permeability, resulted in the identification of 15b and 15e with good activity (IC₅₀=1.6 nM each) and moderate lipophilicity (Log D=2.0, 1.8). Furthermore, 15e demonstrated efficacy in murine asthma model by an oral dose of 30 mg/kg.