Main Article Content
Abstract
In this work, we have performed 3D QSAR study of reported pyridone-pyrimidone derivatives. CoMFA was applied to generate 3D QSAR models. Total eight QSAR models were generated. Model 2 was close to standard set criteria. Effect of steric and electrostatic substituents on biological activity was observed on contour maps. This study will be helpful for future researchers in designing new pyridine-pyrimidone derivatives.
Keywords
Article Details
Copyright (c) 2022 Asian Journal of Organic & Medicinal Chemistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
References
- M.A. Hossain and R. Pervin, Current Antidiabetic Drugs: Review of their Efficacy and Safety, In: Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome, Elsevier, Academic Press: Waltham, Ed.: 2, pp. 455–473 (2018).
- T.O. Johnson and P.S. Humphries, Glucokinase Activators for the Treatment of Type 2 Diabetes, Ann. Rep. Med. Chem., 41, 141 (2006); https://doi.org/10.1016/S0065-7743(06)41008-3
- M. Pal, Recent Advances in Glucokinase Activators for the Treatment of Type 2 Diabetes, Drug Discov. Today, 14, 784 (2009); https://doi.org/10.1016/j.drudis.2009.05.013
- S. Bhattacharya, V. Asati, M. Mishra, R. Das, V. Kashaw and S.K. Kashawa, Integrated Computational Approach on Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors for the Development of Novel Antidiabetic Agents, J. Mol. Struct., 1227, 129511 (2020); https://doi.org/10.1016/j.molstruc.2020.129511
- N. Charaya, D. Pandita, A.S. Grewal and V. Lather, Design, Synthesis and Biological Evaluation of Novel Thiazol-2-yl Benzamide Derivatives as Glucokinase Activators, Comput. Biol. Chem., 73, 221 (2018); https://doi.org/10.1016/j.compbiolchem.2018.02.018
- Z.S. Cheruvallath, S.L. Gwaltney II, M. Sabat, M. Tang, J. Feng, H. Wang, J. Miura, P. Guntupalli, A. Jennings, D. Hosfield, B. Lee and Y. Wu, Design, Synthesis and SAR of Novel Glucokinase Activators, Bioorg. Med. Chem. Lett., 23, 2166 (2013); https://doi.org/10.1016/j.bmcl.2013.01.093
- R.J. Hinklin, B.R. Baer, S.A. Boyd, M.D. Chicarelli, K.R. Condroski, W.E. DeWolf Jr., J. Fischer, M. Frank, G.P. Hingorani, P.A. Lee, N.A. Neitzel, S.A. Pratt, A. Singh, F.X. Sullivan, T. Turner, W.C. Voegtli, E.M. Wallace, L. Williams and T.D. Aicher, Discovery and Preclinical Development of AR453588 as an Anti-diabetic Glucokinase Activator, Bioorg. Med. Chem., 28, 115232 (2019); https://doi.org/10.1016/j.bmc.2019.115232
- J.A. Pfefferkorn, M. Tu, K.J. Filipski, A. Guzman-Perez, J. Bian, G.E. Aspnes, M.F. Sammons, W. Song, J.C. Li, C.S. Jones, L. Patel, T. Rasmusson, D. Zeng, K. Karki, M. Hamilton, R. Hank, K. Atkinson, J. Litchfield, R. Aiello, L. Baker, N. Barucci, P. Bourassa, F. Bourbounais, T. D’Aquila, D.R. Derksen, M. MacDougall and A. Robertson, The Design and Synthesis of Indazole and Pyrazolopyridine Based Glucokinase Activators for the Treatment of Type 2 Diabetes Mellitus, Bioorg. Med. Chem. Lett., 22, 7100 (2012); https://doi.org/10.1016/j.bmcl.2012.09.082
- K.J. Filipski, A. Guzman-Perez, J. Bian, C. Perreault, G.E. Aspnes, M.T. Didiuk, R.L. Dow, R.F. Hank, C.S. Jones, R.J. Maguire, M. Tu, D. Zeng, S. Liu, J.D. Knafels, J. Litchfield, K. Atkinson, D.R. Derksen, F. Bourbonais, K.S. Gajiwala, M. Hickey, T.O. Johnson, P.S. Humphries and J.A. Pfefferkorn, Pyrimidone-Based Series of Glucokinase Activators with Alternative Donor–Acceptor Motif, Bioorg. Med. Chem. Lett., 23, 4571 (2013); https://doi.org/10.1016/j.bmcl.2013.06.036
- R. Ragno, www.3d-qsar.com: A Web Portal that Brings 3-D QSAR to All Electronic Devices—The Py-CoMFA Web Application as Tool to Build Models from Pre-aligned Datasets, J. Comput. Aided Mol. Des., 33, 855 (2019; https://doi.org/10.1007/s10822-019-00231-x
- www.3d-qsar.com
- Y.N. Kumar, J.A. Pradeep Kiran, P.S. Kumar, S. Yeswanth, K. Kalpana, V. Koteswara Rao, P.V.G.K. Sarma and M. Bhaska, Molecular Docking Assessment of Pyridone Derivatives as Glucokinase Activators, J. Clin. Sci. Res., 1, 163 (2012).
References
M.A. Hossain and R. Pervin, Current Antidiabetic Drugs: Review of their Efficacy and Safety, In: Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome, Elsevier, Academic Press: Waltham, Ed.: 2, pp. 455–473 (2018).
T.O. Johnson and P.S. Humphries, Glucokinase Activators for the Treatment of Type 2 Diabetes, Ann. Rep. Med. Chem., 41, 141 (2006); https://doi.org/10.1016/S0065-7743(06)41008-3
M. Pal, Recent Advances in Glucokinase Activators for the Treatment of Type 2 Diabetes, Drug Discov. Today, 14, 784 (2009); https://doi.org/10.1016/j.drudis.2009.05.013
S. Bhattacharya, V. Asati, M. Mishra, R. Das, V. Kashaw and S.K. Kashawa, Integrated Computational Approach on Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors for the Development of Novel Antidiabetic Agents, J. Mol. Struct., 1227, 129511 (2020); https://doi.org/10.1016/j.molstruc.2020.129511
N. Charaya, D. Pandita, A.S. Grewal and V. Lather, Design, Synthesis and Biological Evaluation of Novel Thiazol-2-yl Benzamide Derivatives as Glucokinase Activators, Comput. Biol. Chem., 73, 221 (2018); https://doi.org/10.1016/j.compbiolchem.2018.02.018
Z.S. Cheruvallath, S.L. Gwaltney II, M. Sabat, M. Tang, J. Feng, H. Wang, J. Miura, P. Guntupalli, A. Jennings, D. Hosfield, B. Lee and Y. Wu, Design, Synthesis and SAR of Novel Glucokinase Activators, Bioorg. Med. Chem. Lett., 23, 2166 (2013); https://doi.org/10.1016/j.bmcl.2013.01.093
R.J. Hinklin, B.R. Baer, S.A. Boyd, M.D. Chicarelli, K.R. Condroski, W.E. DeWolf Jr., J. Fischer, M. Frank, G.P. Hingorani, P.A. Lee, N.A. Neitzel, S.A. Pratt, A. Singh, F.X. Sullivan, T. Turner, W.C. Voegtli, E.M. Wallace, L. Williams and T.D. Aicher, Discovery and Preclinical Development of AR453588 as an Anti-diabetic Glucokinase Activator, Bioorg. Med. Chem., 28, 115232 (2019); https://doi.org/10.1016/j.bmc.2019.115232
J.A. Pfefferkorn, M. Tu, K.J. Filipski, A. Guzman-Perez, J. Bian, G.E. Aspnes, M.F. Sammons, W. Song, J.C. Li, C.S. Jones, L. Patel, T. Rasmusson, D. Zeng, K. Karki, M. Hamilton, R. Hank, K. Atkinson, J. Litchfield, R. Aiello, L. Baker, N. Barucci, P. Bourassa, F. Bourbounais, T. D’Aquila, D.R. Derksen, M. MacDougall and A. Robertson, The Design and Synthesis of Indazole and Pyrazolopyridine Based Glucokinase Activators for the Treatment of Type 2 Diabetes Mellitus, Bioorg. Med. Chem. Lett., 22, 7100 (2012); https://doi.org/10.1016/j.bmcl.2012.09.082
K.J. Filipski, A. Guzman-Perez, J. Bian, C. Perreault, G.E. Aspnes, M.T. Didiuk, R.L. Dow, R.F. Hank, C.S. Jones, R.J. Maguire, M. Tu, D. Zeng, S. Liu, J.D. Knafels, J. Litchfield, K. Atkinson, D.R. Derksen, F. Bourbonais, K.S. Gajiwala, M. Hickey, T.O. Johnson, P.S. Humphries and J.A. Pfefferkorn, Pyrimidone-Based Series of Glucokinase Activators with Alternative Donor–Acceptor Motif, Bioorg. Med. Chem. Lett., 23, 4571 (2013); https://doi.org/10.1016/j.bmcl.2013.06.036
R. Ragno, www.3d-qsar.com: A Web Portal that Brings 3-D QSAR to All Electronic Devices—The Py-CoMFA Web Application as Tool to Build Models from Pre-aligned Datasets, J. Comput. Aided Mol. Des., 33, 855 (2019; https://doi.org/10.1007/s10822-019-00231-x
www.3d-qsar.com
Y.N. Kumar, J.A. Pradeep Kiran, P.S. Kumar, S. Yeswanth, K. Kalpana, V. Koteswara Rao, P.V.G.K. Sarma and M. Bhaska, Molecular Docking Assessment of Pyridone Derivatives as Glucokinase Activators, J. Clin. Sci. Res., 1, 163 (2012).