Design, Synthesis and Antidiabetic Activity of Novel Sulfamoyl Benzamide Derivatives as Glucokinase Activators
The present work has been planned to design, synthesize and evaluate the antidiabetic potential of a series of sulfamoyl benzamide derivatives as potential glucokinase (GK) activators. A new series of sulfamoyl benzamide derivatives was synthesized starting from 3-nitrobenzoic acid and characterized. In silico docking studies were performed to determine the binding interactions for the best fit conformations in the allosteric site of GK enzyme. Based on the results of in silico studies, the selected molecules were tested for their antidiabetic activity in animal studies (alloxan induced diabetic animal model). Compound 7 exhibited highest antidiabetic activity in animal studies. The results of in vivo antidiabetic activity studies were found to be in parallel to that of docking studies. These newly synthesized sulfamoyl benzamide derivatives thus can be treated as the initial hits for the development of novel, safe, effective and orally bioavailable GK activators as therapeutic agents for the treatment of type 2 diabetes.
 Bastaki, S. (2005). Diabetes mellitus and its treatment. International Journal of Diabetes Metabolism, 13, 111–134.
 Brownlee, M. (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414, 813–820. https://doi.org/10.1038/414813
 Cade, W. T. (2008). Diabetes-related microvascular and macrovascular diseases in the physical therapy setting. Physical Therapy, 88, 1322–1335. https://doi.org/10.2522/ptj.20080008
 Charaya N., Pandita D., Grewal A. S., and Lather V.(2018). Design, synthesis and biological evaluation of novel thiazol-2-yl benzamide derivatives as glucokinase activators. Computational Biology and Chemistry, 73, 221–229. https://doi.org/10.1016/j.compbiolchem.2018.02.018
 Cheruvallath, Z. S., Gwaltney, S. L., Sabat, M., Tang, M., Feng, J., Wang, H., et al. (2013). Design, synthesis and SAR of novel glucokinase activators. Bioorganic and Medicinal Chemistry Letters, 23(7), 2166–2171. https://doi.org/10.1016/j.bmcl.2013.01.093
 Coghlan, M. and Leighton, B. (2008). Glucokinase activators in diabetes management. Expert Opinion on Investigational Drugs, 17(2), 145–167. https://doi.org/10.1517/13543722.214.171.124
 Filipski, K. J., Guzman-Perez, A., Bian, J., Perreault, C., Aspnes, G. E., Didiuk, M. T., et al. (2013). Pyrimidone-based series of glucokinase activators with alternative donor-acceptor motif. Bioorganic and Medicinal Chemistry Letters, 23(16), 4571–4578. https://doi.org/10.1016/j.bmcl.2013.06.036
 Grewal, A. S., Sekhon, B. S., and Lather, V. (2014). Recent updates on glucokinase activators for the treatment of type 2 diabetes mellitus. Mini Reviews in Medicinal Chemistry, 14(7), 585–602. https://doi.org/10.2174/1389557514666140722082713
 Grewal, A. S., Bhardwaj, S., Pandita, D., Lather, V. and Sekhon, B. S. (2016). Updates on aldose reductase inhibitors for management of diabetic complications and non-diabetic diseases. Mini Reviews in Medicinal Chemistry, 16(2), 120–162. https://doi.org/10.2174/1389557515666150909143737
 Grewal, A. S., Lather, V., Pandita, D. and Bhayana, G. (2017). Synthesis, docking and biological evaluation of phenylacetic acid and trifluoromethylphenyl substituted benzamide derivatives as potential PPARδ agonists. Letters in Drug Design and Discovery, 14(11), 1239–1251. https://doi.org/10.2174/1570180814666170327164443
 Grewal, A. S., Viney Lather, V., Pandita, D. and Dalal, R. (2017). Synthesis, docking and anti-inflammatory activity of triazole amine derivatives as potential phosphodiesterase-4 inhibitors. Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry, 16(1), 58–67. https://doi.org/10.2174/1871523016666170616115752
 Hinklin, R. J., Boyd, S. A., Chicarelli, M. J., Condroski, K. R., DeWolf, W. E., Lee, P. A., et al. (2013). Identification of a new class of glucokinase activators through structure-based design. Journal of Medicinal Chemistry, 56(19), 7669–7678. https://doi.org/10.1021/jm401116k
 Iino, T., Sasaki, Y., Bamba, M., Mitsuya, M., Ohno, A., Kamata, K., et al. (2009). Discovery and structureactivity relationships of a novel class of quinazoline glucokinase activators. Bioorganic and Medicinal Chemistry Letters, 19(19), 5531–5538. https://doi.org/10.1016/j.bmcl.2009.08.064
 Iino, T., Hashimoto, N., Hasegawa, T., Chiba, M., Eiki, J. and Nishimura, T. (2010). Metabolic activation of N-thiazol-2-yl benzamide as glucokinase activators: impacts of glutathione trapping on covalent binding. Bioorganic and Medicinal Chemistry Letters, 20(5), 1619–1622. https://doi.org/10.1016/j.bmcl.2010.01.041
 Ishikawa, M., Nonoshita, K., Ogino, Y., Nagae, Y., Tsukahara, D., Hosaka, H., et al. (2009). Discovery of novel 2-(pyridine-2-yl)-1H-benzimidazole derivatives as potent glucokinase activators. Bioorganic and Medicinal Chemistry Letters, 19(15), 4450–4454. https://doi.org/10.1016/j.bmcl.2009.05.038
 Kohei, K. (2010). Pathophysiology of type 2 diabetes and its treatment policy. Japan Medical Association Journal, 53, 41–46.
 Li, F., Zhu. Q., Zhang, Y., Feng, Y., Leng, Y. and Zhang, A. (2010). Design, synthesis, and pharmacological evaluation of N-(4-mono and 4,5-disubstituted thiazole-2-yl)-2-aryl-3-(tetrahydro-2H-pyran-4-yl) propanamides as glucokinase activators. Bioorganic and Medicinal Chemistry, 18(11), 3875–3884. https://doi.org/10.1016/j.bmc.2010.04.038
 Li, Y. Q., Zhang, Y. L., Hu, S. Q., Wang, Y. L., Song, H. R., Feng, Z.Q. et al. (2011). Design, synthesis and biological evaluation of novel glucokinase activators. Chinese Chemical Letters, 22(1), 73–76. https://doi.org/10.1016/j.cclet.2010.07.023
 Li, Y., Tian, K., Qin, A., Zhang, L., Huo, L., Lei, L. et al. (2014) Discovery of novel urea derivatives as dual-target hypoglycemic agents that activate glucokinase and PPARγ. European Journal of Medicinal Chemistry, 76, 182–192. https://doi.org/10.1016/j.ejmech.2014.02.024
 Mao, W., Ning, M., Liu, Z., Zhu, Q., Leng, Y. and Zhang, A. (2012). Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators. Bioorg. Medicinal Chemistry, 20(9), 2982–2991. https://doi.org/10.1016/j.bmc.2012.03.008
 Matschinsky, F. M. and Porte, D. (2010) Glucokinase activators (GKAs) promise a new pharmacotherapy for diabetics. F1000 Medicine Reports, 2, 43. https://doi.org/10.3410/M2-43
 Matschinsky, F. M., Zelent, B., Doliba, N., Li, C., Vanderkooi, J. M., Naji, A. et al. (2011). Glucokinase activators for diabetes therapy. Diabetes Care, 34, S236–S243. https://doi.org/10.2337/dc11-s236
 Miteva, M. A., Guyon, F. and Tufféry, P. (2010). Frog2: Efficient 3D conformation ensemble generator for small compounds. Nucleic Acids Research, 38, W622–627. https://doi.org/10.1093/nar/gkq325
 Mitsuya, M., Kamata, K., Bamba, M., Watanabe, H., Sasaki, Y., Sasaki, K. et al. (2009). Discovery of novel 3,6-disubstituted 2-pyridinecarboxamide derivatives as GK activators. Bioorganic and Medicinal Chemistry Letters, 19(10), 2718–2721. https://doi.org/10.1016/j.bmcl.2009.03.137
 Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S. et al. (2009). Autodock4 and AutoDockTools4: automated docking with selective receptor flexiblity. Journal of Computational Chemistry, 16, 2785–2791. https://doi.org/10.1002/jcc.21256
 Olokoba, A. B., Obateru, O. A. and Olokoba, L. B. (2012). Type 2 diabetes mellitus: a review of current trends. Oman Medical Journal, 27, 269–273. https://doi.org/10.5001/omj.2012.68
 Pal, M. (2009). Recent advances in glucokinase activators for the treatment of type 2 diabetes. Drug Discovery Today, 14, 784–792. https://doi.org/10.1016/j.drudis.2009.05.013
 Pal, M. (2009a). Medicinal chemistry approaches for glucokinase activation to treat type 2 diabetes. Current Medicinal Chemistry, 16(29), 3858–3874. https://doi.org/10.2174/092986709789177993
 Park, K., Lee, B. M., Kim, Y. H., Han, T., Yi, W., Lee, D.H. et al. (2013). Discovery of a novel phenylethyl benzamide glucokinase activator for the treatment of type 2 diabetes mellitus. Bioorganic and Medicinal Chemistry Letters, 23(2), 537–542. https://doi.org/10.1016/j.bmcl.2012.11.018
 Park, K., Lee, M., Hyun, H., Lee, H., Choi, H., Kim, H. et al. (2014). Discovery of 3-(4-methanesulfonylphenoxy)-N-[1-(2-methoxy-ethoxymethyl)-1Hpyrazol-3-yl]-5-(3-methylpyridin-2-yl)-benzamide as a novel glucokinase activator (GKA) for the treatment of type 2 diabetes mellitus. Bioorganic and Medicinal Chemistry, 22(7), 2280–2293. https://doi.org/10.1016/j.bmc.2014.02.009
 Perseghin, G. (2010). Exploring the in vivo mechanisms of action of glucokinase activators in type 2 diabetes. The Journal of Clinical Endocrinology and Metabolism, 95(11), 4871–4873. https://doi.org/10.1210/jc.2010-2049
 Pfefferkorn, J. A., Guzman-Perez, A., Litchfield, J., Aiello, R., Treadway, J. L., Pettersen, J., et al. (2012). Discovery of (S)-6-(3-cyclopentyl-2-(4-(trifluoromethyl)-1H-imidazol- 1-yl)propanamido) nicotinic acid as a hepatoselective glucokinase activator clinical candidate for treating type 2 diabetes mellitus. Journal of Medicinal Chemistry, 55(3), 1318–1333. https://doi.org/10.1021/jm2014887
 Pfefferkorn, J. A., Tu, M., Filipski, K. J., Guzman- Perez, A., Bian, J., Aspnes, G. E. et al. (2012a). The design and synthesis of indazole and pyrazolopyridine based glucokinase activators for the treatment of type 2 diabetes mellitus. Bioorganic and Medicinal Chemistry Letters, 22(23), 7100–7105. https://doi.org/10.1016/j.bmcl.2012.09.082
 Pike, K. G., Allen, J. V., Caulkett, P. W., Clarke, D. S., Donald, C. S., Fenwick, M. L. et al. (2011). Design of a potent, soluble glucokinase activator with increased pharmacokinetic half-life. Bioorganic and Medicinal Chemistry Letters, 21(11), 3467–3470. https://doi.org/10.1016/j.bmcl.2011.03.093
 Sidduri, A., Grimsby, J. S., Corbett, W. L., Sarabu, R., Grippo, J. F., Lou, J. et al. (2010). 2,3-Disubstituted acrylamides as potent glucokinase activators. Bioorganic and Medicinal Chemistry Letters, 20(19), 5673-5676. https://doi.org/10.1016/j.bmcl.2010.08.029
 Singh, R., Lather, V., Pandita, D., Vikramjeet, J., Karthikeyan, A. N. and Singh, A. S. (2016). Synthesis, docking and antidiabetic activity of some newer benzamide derivatives as potential glucokinase activators. Letters in Drug Design and Discovery, 14(5), 540–553. https://doi.org/10.2174/1570180813666160819125342
 Takahashi, K., Hashimoto, N., Nakama, C., Kamata, K., Sasaki, K., Yoshimoto, R. et al. (2009). The design and optimization of a series of 2-(pyridin-2-yl)-1Hbenzimidazole compounds as allosteric glucokinase activators. Bioorganic and Medicinal Chemistry, 17(19), 7042–7051. https://doi.org/10.1016/j.bmc.2009.05.037
 Trott, O., and Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading. Journal of Computational Chemistry, 31, 455–461.
 Tsumura, Y., Tsushima, Y., Tamura, A., Hasebe, M., Kanou, M., Kato, H. et al. (2017). TMG-123, a novel glucokinase activator, exerts durable effects on hyperglycemia without increasing triglyceride in diabetic animal models. PLoS One, 12(2), e0172252. https://doi.org/10.1371/journal.pone.0172252
 Wang, Z., Shi, X., Zhang, H., Yu, L., Cheng, Y., Zhang, H. et al. (2017). Discovery of cycloalkylfused N-thiazol-2-yl-benzamides as tissue non-specific glucokinase activators: design, synthesis, and biological evaluation. European Journal of Medicinal Chemistry, 139, 128–152. https://doi.org/10.1016/j.ejmech.2017.07.051
 Ye, N., Xu, X., Li, F., Ning, M., Liu, Z., Cao, Y. et al. (2012). Investigation on the oxidation of aryl oxiranylmethanols and the synthesis of 2-aryl-Nthiazolyl-oxirane-2-carboxamides as glucokinase activators. Tetrahedron Letters, 53(35), 4738–4742. https://doi.org/10.1016/j.tetlet.2012.06.111
 Zhang, L., Chen, X., Liu, J., Zhu, Q., Leng, Y., Luo, X. et al. (2012). Discovery of novel dual-action antidiabetic agents that inhibit glycogen phosphorylase and activate glucokinase. European Journal of Medicinal Chemistry, 58, 624–639. https://doi.org/10.1016/j.ejmech.2012.06.020
 Zhang, L., Tian, K., Li, Y., Lei, L., Qin, A., Zhang, L. et al. (2012a). Novel phenyl-urea derivatives as dualtarget ligands that can activate both GK and PPARγ. Acta Pharmaceutica Sinica B, 2(6), 588–597. https://doi.org/10.1016/j.apsb.2012.10.002
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