Exploring QSAR of peripheral benzodiazepine receptor binding affinity of N,N-dialkyl-2-phenylindol-3-yl-glyoxylamides using physico-chemical descriptors.
The present QSAR study has attempted to explore the structural and physicochemical requirements of ligands N,N-dialkyl-2-phenylindol-3-yl-glyoxylamides for binding with peripheral benzodiazepine receptor (PBR). The calculated partition coefficient values show parabolic relations with the PBR binding affinity, suggesting that the binding affinity increases with increase in the partition coefficient of the compounds until it reaches the critical value after which the affinity decreases. The critical value of logP is within range of 6.052-6.410. Furthermore, positive Wang-Ford.charge values of carbonyl oxygens of the glyoxamide moiety and negative Wang-Ford charge value of the glyoxamide nitrogen are conducive for the binding affinity. Again, the indole moiety should have favorable charge distribution. Higher values of the parameters dipole moment (Dipole) and moment of inertia (I_z) of the ligands are conducive for the binding affinity. The presence of hydrogen atom at R2 and cyclic moiety at R1 and R2 positions are detrimental to the binding affinity.
Roy
Kunal
K
Drug Theoretics & Cheminformatics Lab, Division of Medicinal & Pharmaceutical Chemistry, Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700 032, India. kunalroy_in@yahoo.com
Dalai
Manoj Kumar
MK
D000577:Amides / Q000737:chemistry*; D001665:Binding Sites; D006038:Glyoxylates / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D011963:Receptors, GABA-A / Q000737:chemistry* / Q000378:metabolism
D000577:Amides; D006038:Glyoxylates; D007211:Indoles; D011963:Receptors, GABA-A