کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1366054 | 981580 | 2007 | 9 صفحه PDF | دانلود رایگان |

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.
Based on a modelling and iterative approach, a potent dissociated glucocorticoid agonist was discovered where the benzoxazinone is replaced with an aryl pyrazole.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 17, 1 September 2007, Pages 4737–4745