Aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists

SAR leading to the oral selective non-steroidal GR agonist 16e is described. Aryl aminopyrazole amides capped with N-alkylbenzamides 13– 16 are selective glucocorticoid receptor agonists. 2,6-Disubstituted benzamides have prednisolone-like potency or better in vitro. Good oral exposure was demonstra...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009, Vol.19 (1), p.158-162
Hauptverfasser:	Barnett, Heather A., Coe, Diane M., Cooper, Tony W.J., Jack, Torquil I., Jones, Haydn T., Macdonald, Simon J.F., McLay, Iain M., Rayner, Natalie, Sasse, Rosemary Z., Shipley, Tracy J., Skone, Phil A., Somers, Graham I., Taylor, Simon, Uings, Iain J., Woolven, James M., Weingarten, Gordon G.
Format:	Artikel
Sprache:	eng
Schlagworte:	Administration, Oral Aminopyrazole Animals Benzamides - chemical synthesis Benzamides - pharmacology Biological and medical sciences Glucocorticoid Hormones. Endocrine system Humans Hydrophobic and Hydrophilic Interactions Medical sciences Pharmacology. Drug treatments Prednisolone Pyrazoles - chemical synthesis Pyrazoles - pharmacology Rats Receptors, Glucocorticoid - agonists Structure-Activity Relationship
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Zusammenfassung:	SAR leading to the oral selective non-steroidal GR agonist 16e is described. Aryl aminopyrazole amides capped with N-alkylbenzamides 13– 16 are selective glucocorticoid receptor agonists. 2,6-Disubstituted benzamides have prednisolone-like potency or better in vitro. Good oral exposure was demonstrated in the rat, with compounds with lower lipophilicity, for example N-hydroxyethyl benzamides (e.g., 16e).
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2008.10.128