Synthesis of 7,8-disubstituted benzolactam-V8 and its binding to protein kinase C.
7-Methoxy-8-decynyl-benzolactam-V8 4 is synthesized using a catalytic asymmetric alkylation reaction as a key step. This compound shows potent activity to three PKC isozymes tested (Ki =45.6, 91.1, and 121.3 nM to PKCalpha, delta, and epsilon, respectively), indicating that introduction of a suitable substituent at the 7-position of 8-decynyl-benzolactam-V8 only slightly reduces the PKC binding affinity.
Ma
D
D
State Key Laboratory of Bio-organic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences. madw@pub.sioc.ac.cn
Zhang
T
T
Wang
G
G
Kozikowski
A P
AP
Lewin
N E
NE
Blumberg
P M
PM
D001667:Binding, Competitive; D002273:Carcinogens / Q000138:chemical synthesis / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007769:Lactams / Q000138:chemical synthesis* / Q000378:metabolism*; D008235:Lyngbya Toxins / Q000737:chemistry; D015240:Phorbol 12,13-Dibutyrate / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D002273:Carcinogens; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007769:Lactams; D008235:Lyngbya Toxins; C113786:benzolactam V8-310; C022176:teleocidins; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C