Aryl aminopyrazole benzamides as oral non-steroidal selective glucocorticoid receptor agonists.
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).
Barnett
Heather A
HA
Respiratory CEDD, Medicines Research Centre, Stevenage, UK.
Coe
Diane M
DM
Cooper
Tony W J
TW
Jack
Torquil I
TI
Jones
Haydn T
HT
Macdonald
Simon J F
SJ
McLay
Iain M
IM
Rayner
Natalie
N
Sasse
Rosemary Z
RZ
Shipley
Tracy J
TJ
Skone
Phil A
PA
Somers
Graham I
GI
Taylor
Simon
S
Uings
Iain J
IJ
Woolven
James M
JM
Weingarten
Gordon G
GG
D000284:Administration, Oral; D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D011239:Prednisolone; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D013329:Structure-Activity Relationship
D001549:Benzamides; D011720:Pyrazoles; D011965:Receptors, Glucocorticoid; D011239:Prednisolone