Synthesis and modeling study of (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy- 8-(1-decynyl)-benzolactam-V8 as protein kinase C modulators.
[structures: see text] Both (2S,5R,6R)- and (2S,5R,6S)-6-hydroxy-8-(1-decynyl)benzolactam-V8 were designed and synthesized as PKC modulators. Biological assays reveal the (6R)-ligand to be 20-fold more potent than its (6S)-counterpart in binding to PKC alpha.
Wei
Zhi-Liang
ZL
Drug Discovery Program, Department of Neurology, Georgetown University Medical Center, 3900 Reservoir Road, NW, Washington, DC 20007, USA.
Sakamuri
Sukumar
S
Petukhov
Pavel A
PA
George
Clifford
C
Lewin
Nancy E
NE
Blumberg
Peter M
PM
Kozikowski
Alan P
AP
D006860:Hydrogen Bonding; D007769:Lactams / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008958:Models, Molecular; D011485:Protein Binding; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
C466024:6-hydroxy- 8-(1-decynyl)-benzolactam-V8; D007769:Lactams; D008024:Ligands; C113786:benzolactam V8-310; D011493:Protein Kinase C