title: Steroidal C-21 heteroaryl thioethers. Part 3: pregn-4-eno-[3,2-c]pyrazole fused A ring modified steroids as selective glucocorticoid receptor modulators (dissociated steroids).
abstract: The introduction of A ring pyrazole modification to the hydrocortisone C-21 heteroaryl thioethers generated compounds with excellent transrepression potency (IL-8 inhibition) compared to their hydrocortisone analogs. However, the transcriptional transactivation activity of these compounds were considerably higher than the corresponding hydrocortisone analogs. Among all the compounds evaluated, a quinoxaline thioether modification demonstrated the best overall in vitro separation.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. purakkattle.biju@merck.com
authors.forename: Purakkattle
authors.initials: P
authors.lastname: Biju
authors.forename: Hongwu
authors.initials: H
authors.lastname: Wang
authors.forename: John
authors.initials: J
authors.lastname: Anthes
authors.forename: Kevin
authors.initials: K
authors.lastname: McCormick
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: Michael
authors.initials: M
authors.lastname: Berlin
authors.forename: Rema
authors.initials: R
authors.lastname: Bitar
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Lim
authors.forename: Yoon Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Daniel
authors.initials: D
authors.lastname: Prelusky
authors.forename: Robbie
authors.initials: R
authors.lastname: Mcleod
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Jia
authors.forename: Xiomora
authors.initials: X
authors.lastname: Fernandez
authors.forename: Gissela
authors.initials: G
authors.lastname: Lieber
authors.forename: Johanna
authors.initials: J
authors.lastname: Jimenez
authors.forename: Steve
authors.initials: S
authors.lastname: Eckel
authors.forename: Aileen
authors.initials: A
authors.lastname: House
authors.forename: Richard
authors.initials: R
authors.lastname: Chapman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Phillips
mesh_terms: D006801:Humans; D006854:Hydrocortisone; D011720:Pyrazoles / Q000737:chemistry; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D013256:Steroids / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000737:chemistry* / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: D011720:Pyrazoles; D011965:Receptors, Glucocorticoid; D013256:Steroids; D013440:Sulfides; C031280:pyrazole; D006854:Hydrocortisone