862540-79-2Relevant articles and documents
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
Glossop, Paul A.,Lane, Charlotte A. L.,Price, David A.,Bunnage, Mark E.,Lewthwaite, Russell A.,James, Kim,Brown, Alan D.,Yeadon, Michael,Perros-Huguet, Christelle,Trevethick, Michael A.,Clarke, Nicholas P.,Webster, Robert,Jones, Rhys M.,Burrows, Jane L.,Feeder, Neil,Taylor, Stefan C. J.,Spence, Fiona J.
supporting information; experimental part, p. 6640 - 6652 (2010/11/19)
A novel series of potent and selective sulfonamide derived β2-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.
