title: Steroidal C-21 mercapto derivatives as dissociated steroids: discovery of an inhaled dissociated steroid.
abstract: A series of C-21 mercapto derivatives of hydrocortisone have been synthesized and evaluated in cell based transrepression and transactivation assays. The benzothiazole derivative, compound 6 not only showed a dissociated profile in vitro functional assays but also a pharmacological profile in a Brown-Norway rat therapeutic index model of asthma that dissociated side effects (thymolysis) while maintaining efficacy against pulmonary inflammation and lung function.
authors.affiliation: Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. julianbiju@yahoo.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: Richard
authors.initials: R
authors.lastname: Chapman
authors.forename: Robbie
authors.initials: R
authors.lastname: McLeod
authors.forename: Daniel
authors.initials: D
authors.lastname: Prelusky
authors.forename: Stephen
authors.initials: S
authors.lastname: Eckel
authors.forename: George
authors.initials: G
authors.lastname: Kelly
authors.forename: Michelle
authors.initials: M
authors.lastname: Natiello
authors.forename: Aileen
authors.initials: A
authors.lastname: House
authors.forename: Xiomara
authors.initials: X
authors.lastname: Fernandez
authors.forename: Rema
authors.initials: R
authors.lastname: Bitar
authors.forename: Jonathan
authors.initials: J
authors.lastname: Phillips
authors.forename: John
authors.initials: J
authors.lastname: Anthes
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001249:Asthma / Q000188:drug therapy; D002460:Cell Line; D055808:Drug Discovery; D008168:Lung / Q000187:drug effects; D051381:Rats; D013256:Steroids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D013256:Steroids; D013438:Sulfhydryl Compounds