CP-MLR/PLS derived QSAR rationales for the GPR119 agonistic activity of the Indole-based derivatives

[摘要] QSAR study has been carried out on the GPR119 agonistic activity of indole-based derivatives in terms of Dragon descriptors. The derived QSAR models have revealed that the atomic Sandersons electronegativities weighted and charge accounting descriptors ATS7e, GATS1e, GATS4e and GGI8, molecular mass weighted descriptors, MATS7m and BELm5, and atomic polarizabilities weighted descriptors ATS7p and BELp8, and molecular topology accounting feature LovaszPelikan index (LP1) played a pivotal role in rationalization of GPR119 agonistic activity of titled compounds. Hydrophilic factor (Hy) and certain structural fragments, such as CHR2X (C-008), R- -CX--X (C-008) and H attached to heteroatom (H-050) are also predominant to explain GPR119 agonistic actions of indole-based derivatives. PLS analysis has also corroborated the dominance of CP-MLR identified descriptors. Applicability domain analysis revealed that the suggested model matches the high quality parameters with good fitting power and the capability of assessing external data and all of the compounds was within the applicability domain of the proposed model and were evaluated correctly.

[学科分类] 药学

[关键词] QSAR;GPR119 agonistic activity;Combinatorial protocol in multiple linear regression (CP-MLR) analysis;PLS analysis;Dragon descriptors;Indole-based derivatives.