Author/Authors :
Margaret Clackers، نويسنده , , Diane M. Coe، نويسنده , , Derek A. Demaine، نويسنده , , George W. Hardy، نويسنده , , Davina Humphreys، نويسنده , , Graham G.A. Inglis، نويسنده , , Michael J. Johnston، نويسنده , , Haydn T. Jones، نويسنده , , David House، نويسنده , , Richard Loiseau، نويسنده , , Doug J. Minick، نويسنده , , Philip A. Skone، نويسنده , , Iain Uings، نويسنده , , Iain M. McLay، نويسنده , , Simon J.F. MacDonald، نويسنده ,
Abstract :
Starting from an established series of non-steroidal glucocorticoid receptor (GR) agonists, a large array was designed where a metabolically labile benzoxazinone moiety was replaced. Initial hits bound to GR but lacked agonist activity. Following two further iterations, potent GR agonists were discovered with 20D1E1 having NFκB agonism pIC50 8.8 (103%). Other analogues such as 23D1E1 display a dissociated profile (NFκB pIC50 8.1 (103%), MMTV pEC50 7.02 (36%)). The tetrahydronaphthalene moiety can also be replaced with substituted aryls such as 24E1 and 25E1.
Keywords :
Glucocorticoid , Aryl pyrazole , agonist , Dissociated , Tetrahydronaphthalene , non-steroidal
