452339-74-1Relevant academic research and scientific papers
The discovery of long-acting saligenin β2 adrenergic receptor agonists incorporating a urea group
Procopiou, Panayiotis A.,Barrett, Victoria J.,Ford, Alison J.,Looker, Brian E.,Lunniss, Gillian E.,Needham, Deborah,Smith, Claire E.,Somers, Graham
scheme or table, p. 6026 - 6032 (2011/11/07)
A series of novel, potent and selective human β2 adrenoceptor agonists incorporating a urea moiety on the terminal right-hand side phenyl ring of (R)-salmeterol is presented. Urea 9j had long duration of action in vitro on guinea pig trachea, and also in vivo similar to that of salmeterol. It had lower oral absorption and bioavailability than salmeterol in both rat and dog. It had a turnover ratio similar to salmeterol, with no evidence for formation of any aniline metabolites in human liver microsomes and hepatocytes. However no crystalline salts suitable for inhaled delivery were identified.
Synthesis and structure-activity relationships of long-acting β2 adrenergic receptor agonists incorporating arylsulfonamide groups
Procopiou, Panayiotis A.,Barrett, Victoria J.,Bevan, Nicola J.,Biggadike, Keith,Butchers, Peter R.,Coe, Diane M.,Conroy, Richard,Edney, Dean D.,Field, Rita N.,Ford, Alison J.,Guntrip, Stephen B.,Looker, Brian E.,McLay, Iain M.,Monteith, Michael J.,Morrison, Valerie S.,Mutch, Peter J.,Richards, Stephen A.,Sasse, Rosemary,Smith, Claire E.
experimental part, p. 2280 - 2288 (2010/03/25)
A series of saligenin alkoxyalkylphenylsulfonamide β2 adrenoceptor agonists were prepared by reacting a protected saligenin oxazolidinone with alkynyloxyalkyl bromides, followed by Sonogashira reaction, hydrogenation, and deprotection. The meta-substituted primary sulfonamide was more potent than the paraand the ortho-analogues. Primary sulfonamides were more potent than the secondary and tertiary analogues. The onset and duration of action in vitro of selected compounds was assessed on isolated superfused guinea pig trachea. Sulfonamide 29b had the best profile of potency, selectivity, onset, and duration of action on both guinea pig trachea and human bronchus. Furthermore, 29b was found to have low oral bioavailability in rat and dog and also to have long duration of action in an in vivo model of bronchodilation. Crystalline salts of 29b were identified that had suitable properties for inhaled administration. A proposed binding mode for 29b to the β2-receptor is presented.
PHENETHANOLAMINE DERIVATIVES FOR THE TREATMENT OF RESPIRATORY DISEASES
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Page 41-42, (2010/02/06)
The present invention relates to novel compounds of formula (I), to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.
PHENETHANOLAMINE DERIVATIVES FOR TREATMENT OF RESPIRATORY DISEASES
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Page/Page column 47, (2010/02/07)
The present invention relates to novel compounds of formula (I),to a process for their manufacture, to pharmaceutical compositions containing them, and to their use in therapy, in particular their use in the prophylaxis and treatment of respiratory diseases.
