Selection of a 2-azabicyclo [2.2. 2] octane-based α 4 β 1 integrin antagonist as an inhaled anti-asthmatic agent

…, L de Garavilla, BP Damiano, WA Kinney…

Index: Lawson, Edward C.; Santulli, Rosemary J.; Dyatkin, Alexey B.; Ballentine, Scott A.; Abraham, William M.; Rudman, Sandra; Page, Clive P.; de Garavilla, Lawrence; Damiano, Bruce P.; Kinney, William A.; Maryanoff, Bruce E. Bioorganic and Medicinal Chemistry, 2006 , vol. 14, # 12 p. 4208 - 4216

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Citation Number: 9

Abstract

The α4β1 integrin, expressed on eosinophils and neutrophils, induces inflammation in the lung by facilitating cellular infiltration and activation. From a number of potent α4β1 antagonists that we evaluated for safety and efficacy, 1 was selected as a lead candidate for anti-asthma therapy by the inhalation route. We devised an optimized stereoselective synthesis to facilitate the preparation of a sufficiently large quantity of 1 for assessment in ...