Inhalation by Design: Novel Ultra-Long-Acting β2-Adrenoreceptor Agonists for Inhaled Once-Daily Treatment of Asthma and Chronic Obstructive Pulmonary Disease That Utilize a Sulfonamide Agonist Headgroup
Citations Over TimeTop 10% of 2010 papers
Abstract
A novel series of potent and selective sulfonamide derived β(2)-adrenoreceptor agonists are described that exhibit potential as inhaled ultra-long-acting bronchodilators for the treatment of asthma and chronic obstructive pulmonary disease. Analogues from this series mediate very long-lasting smooth muscle relaxation in guinea pig tracheal strips. The sulfonamide agonist headgroup confers high levels of intrinsic crystallinity that could relate to the acidic sulfonamide motif supporting a zwitterionic form in the solid state. Optimization of pharmacokinetic properties was achieved through targeted introduction of a phenolic moiety to support rapid phase II clearance, thereby minimizing systemic exposure following inhalation and reducing systemically mediated adverse events. Compound 38 (PF-610355) is identified as a clinical candidate from this series, with in vivo duration of action studies confirming its potential for once-daily use in humans. Compound 38 is currently in advanced phase II clinical studies.
Related Papers
- → In Vitro Inhibition Effects of some New Sulfonamide Inhibitors on Human Carbonic Anhydrase I and II(2004)7 cited
- → Cholinesterase Activity and Sulfonamide Absorption in Rats(1966)3 cited
- → Nebulisers versus hand-held inhalers to deliver beta2-agonist bronchodilator drugs in non-acute asthma(2010)
- → Nebulisers versus hand-held inhalers to deliver beta2-agonist bronchodilator drugs in non-acute asthma(1999)
- → Deconstructing Protein Binding of Sulfonamides and Sulfonamide Analogs(2023)