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

Heather A Barnett; Diane M Coe; Tony W J Cooper; Torquil I Jack; Haydn T Jones; Simon J F Macdonald; Iain M McLay; Natalie Rayner; Rosemary Z Sasse; Tracy J Shipley; Phil A Skone; Graham I Somers; Simon Taylor; Iain J Uings; James M Woolven; Gordon G Weingarten

doi:10.1016/j.bmcl.2008.10.128

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

Bioorg Med Chem Lett. 2009 Jan 1;19(1):158-62. doi: 10.1016/j.bmcl.2008.10.128. Epub 2008 Nov 5.

Authors

Heather A Barnett¹, Diane M Coe, Tony W J Cooper, Torquil I Jack, Haydn T Jones, Simon J F Macdonald, Iain M McLay, Natalie Rayner, Rosemary Z Sasse, Tracy J Shipley, Phil A Skone, Graham I Somers, Simon Taylor, Iain J Uings, James M Woolven, Gordon G Weingarten

Affiliation

¹ Respiratory CEDD, Medicines Research Centre, Stevenage, UK.

PMID: 19019676
DOI: 10.1016/j.bmcl.2008.10.128

Abstract

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).

MeSH terms

Administration, Oral
Animals
Benzamides / chemical synthesis*
Benzamides / pharmacology
Humans
Hydrophobic and Hydrophilic Interactions
Prednisolone
Pyrazoles / chemical synthesis*
Pyrazoles / pharmacology
Rats
Receptors, Glucocorticoid / agonists*
Structure-Activity Relationship

Substances

Benzamides
Pyrazoles
Receptors, Glucocorticoid
Prednisolone