title: Steroidal C-21 heteroaryl thioethers (Part 2): discovery of orally bioavailable selective glucocorticoid receptor modulators (dissociated steroids).
abstract: The prednisolone C-21 heteroaryl thioethers have been synthesized and evaluated in cell based transrepression and transactivation assays. Most of the compounds demonstrated weak transactivational activity in both human and rat tyrosineaminotransferase functional assay while keeping potent anti-inflammatory activity. The benzimidazole thioether 7 exhibited comparable anti-inflammatory activity and improved safety profile compared to the classical oral steroid prednisolone.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, USA. purakkattle.biju@merck.com
authors.forename: Purakkattle
authors.initials: P
authors.lastname: Biju
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: Daniel
authors.initials: D
authors.lastname: Solomon
authors.forename: Hongwu
authors.initials: H
authors.lastname: Wang
authors.forename: Yoon Joo
authors.initials: YJ
authors.lastname: Lee
authors.forename: Rema
authors.initials: R
authors.lastname: Bitar
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: Stephen
authors.initials: S
authors.lastname: Eckel
authors.forename: Aileen
authors.initials: A
authors.lastname: House
authors.forename: Gissela
authors.initials: G
authors.lastname: Lieber
authors.forename: Johanna
authors.initials: J
authors.lastname: Jimenez
authors.forename: George
authors.initials: G
authors.lastname: Kelly
authors.forename: Richard
authors.initials: R
authors.lastname: Chapman
authors.forename: Jonathan
authors.initials: J
authors.lastname: Phillips
authors.forename: John
authors.initials: J
authors.lastname: Anthes
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D001682:Biological Availability; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D056945:Hep G2 Cells; D006801:Humans; D008968:Molecular Conformation; D051381:Rats; D011914:Rats, Inbred BN; D011965:Receptors, Glucocorticoid / Q000819:agonists* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013440:Sulfides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014444:Tyrosine Transaminase / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011965:Receptors, Glucocorticoid; D013440:Sulfides; D014444:Tyrosine Transaminase