title: Synthesis and protein kinase C inhibitory activities of balanol analogs with replacement of the perhydroazepine moiety.
abstract: Balanol is a potent protein kinase C (PKC) inhibitor that is structurally composed of a benzophenone diacid, a 4-hydroxybenzamide, and a perhydroazepine ring. A number of balanol analogs in which the perhydroazepine moiety is replaced have been synthesized and their biological activities evaluated against both PKC and cAMP-dependent kinase (PKA). The results suggested that the activity and the isozyme/kinase selectivity of these compounds are largely related to the conformation about this nonaromatic structural element of the molecules.
authors.affiliation: Sphinx Pharmaceuticals, A Division of Eli Lilly & Company, Durham, North Carolina 27707, USA.
authors.forename: Y S
authors.initials: YS
authors.lastname: Lai
authors.forename: J S
authors.initials: JS
authors.lastname: Mendoza
authors.forename: G E
authors.initials: GE
authors.lastname: Jagdmann
authors.forename: D S
authors.initials: DS
authors.lastname: Menaldino
authors.forename: C K
authors.initials: CK
authors.lastname: Biggers
authors.forename: J M
authors.initials: JM
authors.lastname: Heerding
authors.forename: J W
authors.initials: JW
authors.lastname: Wilson
authors.forename: S E
authors.initials: SE
authors.lastname: Hall
authors.forename: J B
authors.initials: JB
authors.lastname: Jiang
authors.forename: W P
authors.initials: WP
authors.lastname: Janzen
authors.forename: L M
authors.initials: LM
authors.lastname: Ballas
mesh_terms: D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D062385:Hydroxybenzoates / Q000138:chemical synthesis* / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008968:Molecular Conformation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; D007527:Isoenzymes; C015405:ophiocordin; D011493:Protein Kinase C