3D and quantum QSAR of non-benzodiazepine compounds.
A combined physicochemical and 3D technique is used to establish the QSAR of four series of non-benzodiazepines towards BzR. In physicochemical QSAR study, the semi-empirical PM3 based parameters like hardness, electronegativity, electrophilicity index, molar refractivity, heat of formation, solvent assessable surface area and logP were used as descriptors. The heat of formation (HF) and logP are recognized as the most important descriptors for binding affinity of such compounds to BzR. The 3D QSAR study reveals that beta-Carbolines of series "A" and Imidazo[1, 2-alpha]pyrimidines of series "C" show steric bulk interaction, the beta-Carbolines of series "B" and di-substituted purines of series "D" have dominance of electrostatic interaction with BzR. The CoMSIA also indicate the same trend in terms of steric and electrostatic interaction. The CoMSIA reveals that only in case of series "D", the hydrophobic field effect is important. Some possible candidates for all four series were designed and their probable activities were estimated by using different QSAR models. The activities of designed molecules are in better range and developed models might be helpful to design the potent ligands of BzR.
Pasha
F A
FA
Computational Science Center, Korea Institute of Science and Technology, P.O. Box 131, Cheongryang, Seoul 130-650, Republic of Korea. fpasha@rediffmail.com
Muddassar
M
M
Cho
Seung Joo
SJ
Ahmad
Kaleem
K
Beg
Yakub
Y
D001569:Benzodiazepines / Q000737:chemistry; D002243:Carbolines / Q000737:chemistry / Q000494:pharmacology; D021621:Imaging, Three-Dimensional; D007093:Imidazoles / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship; D012984:Software
D002243:Carbolines; D007093:Imidazoles; D011743:Pyrimidines; D001569:Benzodiazepines; C029899:imidazole; C030986:pyrimidine