The discovery of long-acting saligenin beta(2) adrenergic receptor agonists incorporating a urea group.

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Procopiou PA, Barrett VJ, Ford AJ, Looker BE, Lunniss GE, Needham D, Smith CE, Somers G

The discovery of long-acting saligenin beta(2) adrenergic receptor agonists incorporating a urea group.

Bioorg Med Chem. 2011 Oct 15;19(20):6026-32. doi: 10.1016/j.bmc.2011.08.043. Epub 2011 Aug 26.

PubMed ID

21925889 [ View in PubMed

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Abstract

A series of novel, potent and selective human beta(2) 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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Isoprenaline	Beta-1 adrenergic receptor	EC 50 (nM)	7.94	N/A	N/A	Details
Isoprenaline	Beta-3 adrenergic receptor	EC 50 (nM)	39.81	N/A	N/A	Details
Salmeterol	Beta-1 adrenergic receptor	EC 50 (nM)	794.33	N/A	N/A	Details
Salmeterol	Beta-3 adrenergic receptor	EC 50 (nM)	1258.93	N/A	N/A	Details