3D-QSAR study of benzotriazol-1-yl carboxamide scaffold as monoacylglycerol lipase inhibitors.
OBJECTIVE
The purpose of this study is to build up the 3D pharmacophore of Monoacylglycerol lipase (MAGL) inhibitor and to provide the basis to design the novel and potent MAGL inhibitors.


METHODS
A 3D-QSAR study on benztriazol-1-yl carboxamide derivatives as monoacylglycerol lipase (MAGL) inhibitors was successfully performed by means of pharmacophore mapping using PHASE 3.5 module of Schrφdinger-9.4.


RESULTS
The 3D-QSAR obtained from APRRR-105 hypothesis was found to be statistically good with r(2) = 0.9228 and q(2) = 0.871, taking PLS factor 4. The statistical significance of the model was also confirmed by a high value of Fisher's ratio of 82.8 and a very low value of root-mean-square error (RMSE) 0.2564. Another parameter which signifies the model predictivity is Pearson R. Its value of 0.9512 showed that the correlation between predicted and observed activities for the test set compounds is excellent.


CONCLUSIONS
The study suggested that one H-bond acceptor, one positive center, and proper positioning of hydrophobic groups near the distal aromatic ring C are the crucial determinants for MAGL inhibition. Thus, it can be assumed that the present QSAR analysis is enough to demonstrate MAGL inhibition with the help of APRRR-105 hypothesis and will be helpful in designing novel and potent MAGL inhibitors.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India.
Obaid
O
Afzal
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India.
Suresh
S
Kumar
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India.
Rajiv
R
Kumar
Director of Research and Development in Dabur Research Foundation, Ghaziabad, Uttar Pradesh, India.
Manu
M
Jaggi
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, New Delhi, India.
Sandhya
S
Bawa
3D-QSAR; benztriazol-1-yl carboxamides; monoacylglycerol lipase