文摘
Deuterated and non-deuterated compounds were compared using preclinical assays. Microsomal stability assays can be used to exclude drug candidates but fall short in selection of compounds stable in vivo. A novel analog of XHE-III-74, compound 16, was identified as a potent inhibitor of airway smooth muscle contraction ex vivo. Reduction of airway hyperresponsiveness by 16 in a murine model of asthma was observed despite suboptimal pharmacokinetics.