GQSAR is a breakthrough patent pending methodology that significantly enhances the use of QSAR as an approach for new molecule design. As a predictive tool for activity, this method is significantly superior to conventional 3D and 2D QSAR. Here we explain application of GQSAR for optimizing GPCR compounds in non congeneric series.

1. Fragment Based-GQSAR for GPCR Studies Presenter: Kundan B. Ingale Application Scientist kundani@vlifesciences.com

6. 10/10/11 Representative Molecules Piperazine (C2) Non Ring Nitrogen (C3) 1,2,3,6-tetrahydropyridine (C4) azabicyclo[3.2.1]oct-3-ene (C5) Piperidine (C1)

7. Fragmentation Pattern Fragment R1 (aromatic region): aromatic ring connected with the core of the molecule i.e. fragment R2 Fragment R2 (anchor region): substituent present in the center of the molecule Fragment R3 (flexible region): substituent connected to other end of the fragment R2

8. Relationship between 5HT1A and 5HTT inhibition Design and optimize molecules for multi-target activity r2 = 0.051 Fig: Scatter Plot of pKi_5HT1A Vs pKi_5HTT

11. Model Representation