Synthesis and protein kinase C inhibitory activities of balanol analogs with replacement of the perhydroazepine moiety.
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.
Lai
Y S
YS
Sphinx Pharmaceuticals, A Division of Eli Lilly & Company, Durham, North Carolina 27707, USA.
Mendoza
J S
JS
Jagdmann
G E
GE
Menaldino
D S
DS
Biggers
C K
CK
Heerding
J M
JM
Wilson
J W
JW
Hall
S E
SE
Jiang
J B
JB
Janzen
W P
WP
Ballas
L M
LM
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
D001381:Azepines; D004791:Enzyme Inhibitors; D062385:Hydroxybenzoates; D007527:Isoenzymes; C015405:ophiocordin; D011493:Protein Kinase C