Quantitative structure-activity relationship study on some benzodiazepine derivatives as anti-Alzheimer agents.
A QSAR study was performed in an attempt to explore the pharmacophore of some benzodiazepine derivatives as anti-Alzheimer agents for the inhibition of gamma-secretase. The study, which used the electrotopological state atom (ETSA) index, which encodes electronic and topological information, reveals the importance of two phenyl rings-one substituted and another unsubstituted, for the inhibition of the enzyme. Fluorine substitution on the substituted phenyl ring has an important contribution to the activity. R-configurations of the aliphatic chain substituents provide the exact conformation of the molecules to enter into the binding pockets of the receptor(s). [figure: see text]. General structure of benzodiazepine containing gamma-secretase inhibitors.
Debnath
Bikash
B
Division of Medicinal and Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, PO Box No 17020, 700 032, Kolkata, India.
Gayen
Shovanlal
S
Basu
Anindya
A
Srikanth
Kolluru
K
Jha
Tarun
T
D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases; D001569:Benzodiazepines / Q000737:chemistry* / Q000494:pharmacology*; D010450:Endopeptidases / Q000187:drug effects; D008958:Models, Molecular; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship
D011480:Protease Inhibitors; D001569:Benzodiazepines; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases