Revefenacin Absorption, Metabolism, and Excretion in Healthy Subjects and Pharmacological Activity of Its Major Metabolite.

Revefenacin inhalation solution is an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease. Mass balance, pharmacokinetics, and metabolism of revefenacin were evaluated after intravenous and oral administration of [C]-revefenacin in healthy subjects. Pharmacological activity of the major revefenacin metabolite was also assessed.

Discovery of Axelopran (TD-1211): A Peripherally Restricted μ-Opioid Receptor Antagonist.

The effects of opioids in the central nervous system (CNS) provide significant benefit in the treatment of pain but can also lead to physical dependence and addiction, which has contributed to a growing opioid epidemic in the United States. Gastrointestinal dysfunction is an additional serious consequence of opioid use, and this can be treated with a localized drug distribution of a non-CNS penetrant, peripherally restricted opioid receptor antagonist. Herein, we describe the application of Theravance's multivalent approach to drug discovery coupled with a physicochemical property design strategy by which the -substituted--3-(8-aza-bicyclo[3.

Practical enantioselective synthesis of beta-substituted-beta-amino esters.

[reaction: see text] A practical, large-scale synthesis of a beta-amino ester 1 was developed. A chiral imine derived from (S)-phenylglycinol and 3-trimethylsilylpropanal was coupled with the Reformatsky reagent 3 with high diastereoselectivity (de > 98%) to give (SS)-4a as the major isomer. The amino alcohol residue of the coupling product 4 was oxidatively cleaved with sodium periodate in the presence of methylamine.