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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

Integrated Protocol to Design Potential Inhibitors of Dipeptidyl Peptidase- 4 (DPP-4)

Author(s): Simone Queiroz Pantaleão, Eric Allison Philot, Michell de Oliveira Almeida, Angelica Nakagawa Lima, Mirela Inês de Sairre, Ana Ligia Scott and Kathia Maria Honorio*

Volume 20, Issue 3, 2020

Page: [209 - 226] Pages: 18

DOI: 10.2174/1568026620666191226101543

Price: $65

Abstract

Background: A strategy for the treatment of type II diabetes mellitus is the inhibition of the enzyme known as dipeptidyl peptidase-4 (DPP-4).

Aims: This study aims to investigate the main interactions between DPP-4 and a set of inhibitors, as well as proposing potential candidates to inhibit this enzyme.

Methods: We performed molecular docking studies followed by the construction and validation of CoMFA and CoMSIA models. The information provided from these models was used to aid in the search for new candidates to inhibit DPP-4 and the design of new bioactive ligands from structural modifications in the most active molecule of the studied series.

Results: We were able to propose a set of analogues with biological activity predicted by the CoMFA and CoMSIA models, suggesting that our protocol can be used to guide the design of new DPP-4 inhibitors as drug candidates to treat diabetes.

Conclusion: Once the integration of the techniques mentioned in this article was effective, our strategy can be applied to design possible new DPP-4 inhibitors as candidates to treat diabetes.

Keywords: DPP-4, Diabetes, Molecular docking, CoMFA, CoMSIA, Drug design.

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[1]
Kester, M. Farmacologia; Elsevier: Amsterdam, 2008.
[2]
Baynes, J.; Dominiczak, M.H. Bioquimica Medica; Elsevier: Brasil, 2017, pp. 283-307.
[3]
Zhong, J.; Maiseyeu, A.; Davis, S.N.; Rajagopalan, S. DPP4 in Cardiometabolic Disease Recent Insights From the Laboratory and Clinical Trials of DPP4 Inhibition. DPP4 in cardiometabolic disease: recent insights from the laboratory and clinical trials of DPP4 inhibition. Circ. Res., 2015, 116(8), 1491-1504.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.305665] [PMID: 25858071]
[4]
Maltarollo, V.G.; Silva, D.C.; Honorio, K.M. Advanced QSAR studies on PPAR delta ligands related to metabolic diseases. J. Braz. Chem. Soc., 2012, 23, 85-U421.
[5]
Araujo, S.C.; Maltarollo, V.G.; Honorio, K.M. Computational studies of TGF-beta RI (ALK-5) inhibitors: Analysis of the binding interactions between ligand-receptor using 2D and 3D techniques. Eur. J. Pharm. Sci., 2013, 49, 542-549.
[6]
Garcia, T.S.; Silva, D.C.; Gertrudes, J.C.; Maltarollo, V.G.; Honorio, K.M. Molecular features related to the binding mode of PPAR delta agonists from QSAR and docking analyses. SAR and QSAR Environ. Res., 2013, 24, 157-173.
[7]
Durrant, J.D.; McCammon, J.A. BINANA: a novel algorithm for ligand-binding characterization. J. Mol. Graph. Model., 2011, 29(6), 888-893.
[http://dx.doi.org/10.1016/j.jmgm.2011.01.004] [PMID: 21310640]
[8]
Banno, Y.; Miyamoto, Y.; Sasaki, M.; Oi, S.; Asakawa, T.; Kataoka, O.; Takeuchi, K.; Suzuki, N.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, A.; Funami, M.; Tawada, M.; Yamamoto, Y.; Aertgeerts, K.; Yano, J.; Maezaki, H. Identification of 3-aminomethyl-1,2-dihydro-4-phenyl-1-isoquinolones: a new class of potent, selective, and orally active non-peptide dipeptidyl peptidase IV inhibitors that form a unique interaction with Lys554. Bioorg. Med. Chem., 2011, 19(16), 4953-4970.
[http://dx.doi.org/10.1016/j.bmc.2011.06.059] [PMID: 21764322]
[9]
Maezaki, H.; Banno, Y.; Miyamoto, Y.; Moritoh, Y.; Asakawa, T.; Kataoka, O.; Takeuchi, K.; Suzuki, N.; Ikedo, K.; Kosaka, T.; Sasaki, M.; Tsubotani, S.; Tani, A.; Funami, M.; Yamamoto, Y.; Tawada, M.; Aertgeerts, K.; Yano, J.; Oi, S. Discovery of potent, selective, and orally bioavailable quinoline-based dipeptidyl peptidase IV inhibitors targeting Lys554. Bioorg. Med. Chem., 2011, 19(15), 4482-4498.
[http://dx.doi.org/10.1016/j.bmc.2011.06.032] [PMID: 21741847]
[10]
Miyamoto, Y.; Banno, Y.; Yamashita, T.; Fujimoto, T.; Oi, S.; Moritoh, Y.; Asakawa, T.; Kataoka, O.; Takeuchi, K.; Suzuki, N.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, A.; Funami, M.; Amano, M.; Yamamoto, Y.; Aertgeerts, K.; Yano, J.; Maezaki, H. Design and synthesis of 3-pyridylacetamide derivatives as dipeptidyl peptidase IV (DPP-4) inhibitors targeting a bidentate interaction with Arg125. Bioorg. Med. Chem., 2011, 19(1), 172-185.
[http://dx.doi.org/10.1016/j.bmc.2010.11.038] [PMID: 21163664]
[11]
Miyamoto, Y.; Banno, Y.; Yamashita, T.; Fujimoto, T.; Oi, S.; Moritoh, Y.; Asakawa, T.; Kataoka, O.; Yashiro, H.; Takeuchi, K.; Suzuki, N.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, A.; Sasaki, M.; Funami, M.; Amano, M.; Yamamoto, Y.; Aertgeerts, K.; Yano, J.; Maezaki, H. Discovery of a 3-pyridylacetic acid derivative (TAK-100) as a potent, selective and orally active dipeptidyl peptidase IV (DPP-4) inhibitor. J. Med. Chem., 2011, 54(3), 831-850.
[http://dx.doi.org/10.1021/jm101236h] [PMID: 21218817]
[12]
The MathWorks. MATLAB and Statistics Toolbox Release; Massachusetts, United States, 2012.
[13]
Avogadro Chemistry. Avogadro: an open-source molecular builder and visualization tool. Version 1.2.0., Available at:. http://avogadro.cc/
[14]
Hanwell, M.D.; Curtis, D.E.; Lonie, D.C.; Vandermeersch, T.; Zurek, E.; Hutchison, G.R. Avogadro: an advanced semantic chemical editor, visualization, and analysis platform. J. Cheminform., 2012, 4(1), 17.
[http://dx.doi.org/10.1186/1758-2946-4-17] [PMID: 22889332]
[15]
ChemAxon. MarvinSketch (version 6.2.2), calculation module. Available at:. http://www.chemaxon.com/products/marvin/ marvinsketch/2014.
[16]
Internacional., S.H.R.-T., SYBYL 8.1 Available at:. www.tripos.com
[17]
Stewart, J.J.P. Optimization of parameters for semiempirical methods II. Applications. J. Comput. Chem., 1989, 10, 209-220.
[18]
CCDC. GOLD - Protein ligand docking software. Available from:. http://www.ccdc.cam.ac.uk/products/life_sciences/gold
[19]
Sutton, J.M.; Clark, D.E.; Dunsdon, S.J.; Fenton, G.; Fillmore, A.; Harris, N.V.; Higgs, C.; Hurley, C.A.; Krintel, S.L.; MacKenzie, R.E.; Duttaroy, A.; Gangl, E.; Maniara, W.; Sedrani, R.; Namoto, K.; Ostermann, N.; Gerhartz, B.; Sirockin, F.; Trappe, J.; Hassiepen, U.; Baeschlin, D.K. Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2012, 22(3), 1464-1468.
[http://dx.doi.org/10.1016/j.bmcl.2011.11.054] [PMID: 22177783]
[20]
Sutton, J.M. Erratum to “Novel heterocyclic DPP-4 inhibitors for the treatment of type 2 diabetes”. Bioorg. Med. Chem. Lett., 2012, 22(6), 2359.
[http://dx.doi.org/10.1016/j.bmcl.2012.01.109]
[21]
Bjelke, J.R.; Christensen, J.; Branner, S.; Wagtmann, N.; Olsen, C.; Kanstrup, A.B.; Rasmussen, H.B. Tyrosine 547 constitutes an essential part of the catalytic mechanism of dipeptidyl peptidase IV. J. Biol. Chem., 2004, 279(33), 34691-34697.
[http://dx.doi.org/10.1074/jbc.M405400200] [PMID: 15175333]
[22]
Pantaleao, S.Q.; Maltarollo, V.G.; Araujo, S.C.; Gertrudes, J.C.; Honorio, K.M. Molecular docking studies and 2D analyses of DPP-4 inhibitors as candidates in the treatment of diabetes. Mol. Biosyst., 2015, 11(11), 3188-3193.
[http://dx.doi.org/10.1039/C5MB00493D] [PMID: 26399297]
[23]
Pettersen, E.F.; Goddard, T.D.; Huang, C.C.; Couch, G.S.; Greenblatt, D.M.; Meng, E.C.; Ferrin, T.E. UCSF Chimera--a visualization system for exploratory research and analysis. J. Comput. Chem., 2004, 25(13), 1605-1612.
[http://dx.doi.org/10.1002/jcc.20084] [PMID: 15264254]
[24]
Geladi, P.; Kowalski, B.R. Partial least-squares regression: a tutorial. Anal. Chim. Acta, 1986, 185, 1-17.
[http://dx.doi.org/10.1016/0003-2670(86)80028-9]
[25]
Rasmussen, H.B. Crystal structure of human dipeptidyl peptidase IV/CD26 in complex with a substrate analog. Nat. Struct. Biol., 2003, 10(1), 19-25.
[http://dx.doi.org/10.1038/nsb882]
[26]
Peters, J.U.; Weber, S.; Kritter, S.; Weiss, P.; Wallier, A.; Boehringer, M.; Hennig, M.; Kuhn, B.; Loeffler, B.M. Aminomethylpyrimidines as novel DPP-IV inhibitors: a 10(5)-fold activity increase by optimization of aromatic substituents. Bioorg. Med. Chem. Lett., 2004, 14(6), 1491-1493.
[http://dx.doi.org/10.1016/j.bmcl.2004.01.019] [PMID: 15006388]
[27]
Kim, D.; Wang, L.; Beconi, M.; Eiermann, G.J.; Fisher, M.H.; He, H.; Hickey, G.J.; Kowalchick, J.E.; Leiting, B.; Lyons, K.; Marsilio, F.; McCann, M.E.; Patel, R.A.; Petrov, A.; Scapin, G.; Patel, S.B.; Roy, R.S.; Wu, J.K.; Wyvratt, M.J.; Zhang, B.B.; Zhu, L.; Thornberry, N.A.; Weber, A.E. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2005, 48(1), 141-151.
[http://dx.doi.org/10.1021/jm0493156] [PMID: 15634008]
[28]
Qiao, L.; Baumann, C.A.; Crysler, C.S.; Ninan, N.S.; Abad, M.C.; Spurlino, J.C.; Desjarlais, R.L.; Kervinen, J.; Neeper, M.P.; Bayoumy, S.S.; Williams, R.; Deckman, I.C.; Dasgupta, M.; Reed, R.L.; Huebert, N.D.; Tomczuk, B.E.; Moriarty, K.J. Discovery, SAR, and X-ray structure of novel biaryl-based dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(1), 123-128.
[http://dx.doi.org/10.1016/j.bmcl.2005.09.037] [PMID: 16236500]
[29]
Nordhoff, S.; Cerezo-Gálvez, S.; Feurer, A.; Hill, O.; Matassa, V.G.; Metz, G.; Rummey, C.; Thiemann, M.; Edwards, P.J. The reversed binding of β-phenethylamine inhibitors of DPP-IV: X-ray structures and properties of novel fragment and elaborated inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(6), 1744-1748.
[http://dx.doi.org/10.1016/j.bmcl.2005.11.103] [PMID: 16376544]
[30]
Edmondson, S.D.; Mastracchio, A.; Mathvink, R.J.; He, J.; Harper, B.; Park, Y.J.; Beconi, M.; Di Salvo, J.; Eiermann, G.J.; He, H.; Leiting, B.; Leone, J.F.; Levorse, D.A.; Lyons, K.; Patel, R.A.; Patel, S.B.; Petrov, A.; Scapin, G.; Shang, J.; Roy, R.S.; Smith, A.; Wu, J.K.; Xu, S.; Zhu, B.; Thornberry, N.A.; Weber, A.E. (2S,3S)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]-pyridin-6-ylphenyl)butanamide: a selective α-amino amide dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2006, 49(12), 3614-3627.
[http://dx.doi.org/10.1021/jm060015t] [PMID: 16759103]
[31]
Pei, Z.; Li, X.; Longenecker, K.; von Geldern, T.W.; Wiedeman, P.E.; Lubben, T.H.; Zinker, B.A.; Stewart, K.; Ballaron, S.J.; Stashko, M.A.; Mika, A.K.; Beno, D.W.; Long, M.; Wells, H.; Kempf-Grote, A.J.; Madar, D.J.; McDermott, T.S.; Bhagavatula, L.; Fickes, M.G.; Pireh, D.; Solomon, L.R.; Lake, M.R.; Edalji, R.; Fry, E.H.; Sham, H.L.; Trevillyan, J.M. Discovery, structure-activity relationship, and pharmacological evaluation of (5-substituted-pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidines as potent dipeptidyl peptidase IV inhibitors. J. Med. Chem., 2006, 49(12), 3520-3535.
[http://dx.doi.org/10.1021/jm051283e] [PMID: 16759095]
[32]
Xu, J.; Wei, L.; Mathvink, R.J.; Edmondson, S.D.; Eiermann, G.J.; He, H.; Leone, J.F.; Leiting, B.; Lyons, K.A.; Marsilio, F.; Patel, R.A.; Patel, S.B.; Petrov, A.; Scapin, G.; Wu, J.K.; Thornberry, N.A.; Weber, A.E. Discovery of potent, selective, and orally bioavailable oxadiazole-based dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2006, 16(20), 5373-5377.
[http://dx.doi.org/10.1016/j.bmcl.2006.07.061] [PMID: 16919457]
[33]
Madar, D.J. Discovery of 2-[4-2-(2S,5R)-2-Cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl]amino]-4-methyl-1-piperidinyl]-4-pyridi-necarboxylic Acid (ABT-279): A very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-iv, useful for the treatment of diabetes. J. Med. Chem., 2006, 49(21), 6416-6420.
[http://dx.doi.org/10.1021/jm060777o] [PMID: 17034148]
[34]
Pei, Z.; Li, X.; vonGeldern, T.W.; Madar, D.J.; L. Longenecker, K.; Yong, H.; Lubben, T.H.; Stewart, K.D.; Zinker, B.A.; Backes, B.J.; Judd, A.S.; Mulhern, M.; Ballaron, S.J.; Stashko, M.A.; Mika, A.K.; Beno, D.W.A.; Reinhart, G.A.; Fryer, R.M.; Preusser, L.C.; Kempf-Grote, A.J.; Sham, H.L.; Trevillyan, J.M. Discovery of cyclohexene-constrained phenethylamine abt-341, a highly potent, selective, orally bioavailable, safe and potential next-generation dipeptidyl peptidase iv inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2006, 49(22), 6439-6442.http://www.rcsb.org/pdb/explore/explore.do?structureId=2I78
[35]
Biftu, T. (3R)-4-1(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl -3-(2,2,2-trifluo roethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2007, 17(1), 49-52.
[http://dx.doi.org/10.1016/j.bmcl.2006.09.099] [PMID: 17055272]
[36]
Lübbers, T.; Böhringer, M.; Gobbi, L.; Hennig, M.; Hunziker, D.; Kuhn, B.; Löffler, B.; Mattei, P.; Narquizian, R.; Peters, J.U.; Ruff, Y.; Wessel, H.P.; Wyss, P. 1,3-disubstituted 4-aminopiperidines as useful tools in the optimization of the 2-aminobenzo[a]quinolizine dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(11), 2966-2970.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.072] [PMID: 17418568]
[37]
Backes, B.J.; Longenecker, K.; Hamilton, G.L.; Stewart, K.; Lai, C.; Kopecka, H.; von Geldern, T.W.; Madar, D.J.; Pei, Z.; Lubben, T.H.; Zinker, B.A.; Tian, Z.; Ballaron, S.J.; Stashko, M.A.; Mika, A.K.; Beno, D.W.; Kempf-Grote, A.J.; Black-Schaefer, C.; Sham, H.L.; Trevillyan, J.M. Pyrrolidine-constrained phenethylamines: The design of potent, selective, and pharmacologically efficacious dipeptidyl peptidase IV (DPP4) inhibitors from a lead-like screening hit. Bioorg. Med. Chem. Lett., 2007, 17(7), 2005-2012.
[http://dx.doi.org/10.1016/j.bmcl.2007.01.026] [PMID: 17276063]
[38]
Sheehan, S.M.; Mest, H.J.; Watson, B.M.; Klimkowski, V.J.; Timm, D.E.; Cauvin, A.; Parsons, S.H.; Shi, Q.; Canada, E.J.; Wiley, M.R.; Ruehter, G.; Evers, B.; Petersen, S.; Blaszczak, L.C.; Pulley, S.R.; Margolis, B.J.; Wishart, G.N.; Renson, B.; Hankotius, D.; Mohr, M.; Zechel, J.C.; Michael Kalbfleisch, J.; Dingess-Hammond, E.A.; Boelke, A.; Weichert, A.G. Discovery of non-covalent dipeptidyl peptidase IV inhibitors which induce a conformational change in the active site. Bioorg. Med. Chem. Lett., 2007, 17(6), 1765-1768.
[http://dx.doi.org/10.1016/j.bmcl.2006.12.074] [PMID: 17239592]
[39]
Ahn, J.H.; Shin, M.S.; Jun, M.A.; Jung, S.H.; Kang, S.K.; Kim, K.R.; Rhee, S.D.; Kang, N.S.; Kim, S.Y.; Sohn, S.K.; Kim, S.G.; Jin, M.S.; Lee, J.O.; Cheon, H.G.; Kim, S.S. Synthesis, biological evaluation and structural determination of β-aminoacyl-containing cyclic hydrazine derivatives as dipeptidyl peptidase IV (DPP-IV) inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(9), 2622-2628.
[http://dx.doi.org/10.1016/j.bmcl.2007.01.111] [PMID: 17331715]
[40]
Feng, J.; Zhang, Z.; Wallace, M.B.; Stafford, J.A.; Kaldor, S.W.; Kassel, D.B.; Navre, M.; Shi, L.; Skene, R.J.; Asakawa, T.; Takeuchi, K.; Xu, R.; Webb, D.R.; Gwaltney, S.L., II Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV. J. Med. Chem., 2007, 50(10), 2297-2300.
[http://dx.doi.org/10.1021/jm070104l] [PMID: 17441705]
[41]
Duffy, J.L.; Kirk, B.A.; Wang, L.; Eiermann, G.J.; He, H.; Leiting, B.; Lyons, K.A.; Patel, R.A.; Patel, S.B.; Petrov, A.; Scapin, G.; Wu, J.K.; Thornberry, N.A.; Weber, A.E. 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV. Bioorg. Med. Chem. Lett., 2007, 17(10), 2879-2885.
[http://dx.doi.org/10.1016/j.bmcl.2007.02.066] [PMID: 17350841]
[42]
Pei, Z.; Li, X.; von Geldern, T.W.; Longenecker, K.; Pireh, D.; Stewart, K.D.; Backes, B.J.; Lai, C.; Lubben, T.H.; Ballaron, S.J.; Beno, D.W.; Kempf-Grote, A.J.; Sham, H.L.; Trevillyan, J.M. Discovery and structure-activity relationships of piperidinone- and piperidine-constrained phenethylamines as novel, potent, and selective dipeptidyl peptidase IV inhibitors. J. Med. Chem., 2007, 50(8), 1983-1987.
[http://dx.doi.org/10.1021/jm061436d] [PMID: 17367123]
[43]
Biftu, T.; Scapin, G.; Singh, S.; Feng, D.; Becker, J.W.; Eiermann, G.; He, H.; Lyons, K.; Patel, S.; Petrov, A.; Sinha-Roy, R.; Zhang, B.; Wu, J.; Zhang, X.; Doss, G.A.; Thornberry, N.A.; Weber, A.E. Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin. Bioorg. Med. Chem. Lett., 2007, 17(12), 3384-3387.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.095] [PMID: 17433672]
[44]
Wright, S.W.; Ammirati, M.J.; Andrews, K.M.; Brodeur, A.M.; Danley, D.E.; Doran, S.D.; Lillquist, J.S.; Liu, S.; McClure, L.D.; McPherson, R.K.; Olson, T.V.; Orena, S.J.; Parker, J.C.; Rocke, B.N.; Soeller, W.C.; Soglia, C.B.; Treadway, J.L.; Vanvolkenburg, M.A.; Zhao, Z.; Cox, E.D. (3R,4S)-4-(2,4,5-Trifluorophenyl)-pyrrolidin-3-ylamine inhibitors of dipeptidyl peptidase IV: synthesis, in vitro, in vivo, and X-ray crystallographic characterization. Bioorg. Med. Chem. Lett., 2007, 17(20), 5638-5642.
[http://dx.doi.org/10.1016/j.bmcl.2007.07.081] [PMID: 17822893]
[45]
Koo, K.D.; Kim, M.J.; Kim, S.; Kim, K.H.; Hong, S.Y.; Hur, G.C.; Yim, H.J.; Kim, G.T.; Han, H.O.; Kwon, O.H.; Kwon, T.S.; Koh, J.S.; Lee, C.S. Synthesis, SAR, and X-ray structure of novel potent DPPIV inhibitors: oxadiazolyl ketones. Bioorg. Med. Chem. Lett., 2007, 17(15), 4167-4172.
[http://dx.doi.org/10.1016/j.bmcl.2007.05.046] [PMID: 17544668]
[46]
Kowalchick, J.E.; Leiting, B.; Pryor, K.D.; Marsilio, F.; Wu, J.K.; He, H.; Lyons, K.A.; Eiermann, G.J.; Petrov, A.; Scapin, G.; Patel, R.A.; Thornberry, N.A.; Weber, A.E.; Kim, D. Design, synthesis, and biological evaluation of triazolopiperazine-based β-amino amides as potent, orally active dipeptidyl peptidase IV (DPP-4) inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(21), 5934-5939.
[http://dx.doi.org/10.1016/j.bmcl.2007.07.100] [PMID: 17827003]
[47]
Kaelin, D.E.; Smenton, A.L.; Eiermann, G.J.; He, H.; Leiting, B.; Lyons, K.A.; Patel, R.A.; Patel, S.B.; Petrov, A.; Scapin, G.; Wu, J.K.; Thornberry, N.A.; Weber, A.E.; Duffy, J.L. 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV. Bioorg. Med. Chem. Lett., 2007, 17(21), 5806-5811.
[http://dx.doi.org/10.1016/j.bmcl.2007.08.049] [PMID: 17851076]
[48]
Eckhardt, M.; Langkopf, E.; Mark, M.; Tadayyon, M.; Thomas, L.; Nar, H.; Pfrengle, W.; Guth, B.; Lotz, R.; Sieger, P.; Fuchs, H.; Himmelsbach, F. 8-(3-(R)-aminopiperidin-1-yl)-7-but-2-ynyl-3-methyl-1-(4-methyl-quinazolin-2-ylmethyl)-3,7-dihydropurine-2,6-dione (BI 1356), a highly potent, selective, long-acting, and orally bioavailable DPP-4 inhibitor for the treatment of type 2 diabetes. J. Med. Chem., 2007, 50(26), 6450-6453.
[http://dx.doi.org/10.1021/jm701280z] [PMID: 18052023]
[49]
Corbett, J.W.; Dirico, K.; Song, W.; Boscoe, B.P.; Doran, S.D.; Boyer, D.; Qiu, X.; Ammirati, M.; Vanvolkenburg, M.A.; McPherson, R.K.; Parker, J.C.; Cox, E.D. Design and synthesis of potent amido- and benzyl-substituted cis-3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl DPP-IV inhibitors. Bioorg. Med. Chem. Lett., 2007, 17(24), 6707-6713.
[http://dx.doi.org/10.1016/j.bmcl.2007.10.063] [PMID: 17977724]
[50]
Metzler, W.J.; Yanchunas, J.; Weigelt, C.; Kish, K.; Klei, H.E.; Xie, D.; Zhang, Y.; Corbett, M.; Tamura, J.K.; He, B.; Hamann, L.G.; Kirby, M.S.; Marcinkeviciene, J. Involvement of DPP-IV catalytic residues in enzyme-saxagliptin complex formation. Protein Sci., 2008, 17(2), 240-250.
[http://dx.doi.org/10.1110/ps.073253208] [PMID: 18227430]
[51]
Edmondson, S.D.; Wei, L.; Xu, J.; Shang, J.; Xu, S.; Pang, J.; Chaudhary, A.; Dean, D.C.; He, H.; Leiting, B.; Lyons, K.A.; Patel, R.A.; Patel, S.B.; Scapin, G.; Wu, J.K.; Beconi, M.G.; Thornberry, N.A.; Weber, A.E. Fluoroolefins as amide bond mimics in dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(7), 2409-2413.
[http://dx.doi.org/10.1016/j.bmcl.2008.02.050] [PMID: 18331795]
[52]
Wallace, M.B.; Feng, J.; Zhang, Z.; Skene, R.J.; Shi, L.; Caster, C.L.; Kassel, D.B.; Xu, R.; Gwaltney, S.L. II Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(7), 2362-2367.
[http://dx.doi.org/10.1016/j.bmcl.2008.02.071] [PMID: 18346892]
[53]
Liang, G-B.; Qian, X.; Biftu, T.; Singh, S.; Gao, Y.D.; Scapin, G.; Patel, S.; Leiting, B.; Patel, R.; Wu, J.; Zhang, X.; Thornberry, N.A.; Weber, A.E. Discovery of new binding elements in DPP-4 inhibition and their applications in novel DPP-4 inhibitor design. Bioorg. Med. Chem. Lett., 2008, 18(13), 3706-3710.
[http://dx.doi.org/10.1016/j.bmcl.2008.05.061] [PMID: 18524582]
[54]
Ahn, J.H.; Park, W.S.; Jun, M.A.; Shin, M.S.; Kang, S.K.; Kim, K.Y.; Rhee, S.D.; Bae, M.A.; Kim, K.R.; Kim, S.G.; Kim, S.Y.; Sohn, S.K.; Kang, N.S.; Lee, J.O.; Lee, D.H.; Cheon, H.G.; Kim, S.S. Synthesis and biological evaluation of homopiperazine derivatives with β-aminoacyl group as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2008, 18(24), 6525-6529.
[http://dx.doi.org/10.1016/j.bmcl.2008.10.076] [PMID: 18996694]
[55]
Ammirati, M.J.; Andrews, K.M.; Boyer, D.D.; Brodeur, A.M.; Danley, D.E.; Doran, S.D.; Hulin, B.; Liu, S.; McPherson, R.K.; Orena, S.J.; Parker, J.C.; Polivkova, J.; Qiu, X.; Soglia, C.B.; Treadway, J.L.; VanVolkenburg, M.A.; Wilder, D.C.; Piotrowski, D.W. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrrolidin-2-yl]-methanone: a potent, selective, orally active dipeptidyl peptidase IV inhibitor. Bioorg. Med. Chem. Lett., 2009, 19(7), 1991-1995.
[http://dx.doi.org/10.1016/j.bmcl.2009.02.041] [PMID: 19275964]
[56]
Zhang, Z.; Wallace, M.B.; Feng, J.; Stafford, J.A.; Skene, R.J.; Shi, L.; Lee, B.; Aertgeerts, K.; Jennings, A.; Xu, R.; Kassel, D.B.; Kaldor, S.W.; Navre, M.; Webb, D.R.; Gwaltney, S.L. Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV. J. Med. Chem., 2011, 54(2), 510-524.
[http://dx.doi.org/10.1021/jm101016w] [PMID: 21186796]
[57]
Clark, A.R.; Sawyer, G.M.; Robertson, S.P.; Sutherland-Smith, A.J. Skeletal dysplasias due to filamin A mutations result from a gain-of-function mechanism distinct from allelic neurological disorders. Hum. Mol. Genet., 2009, 18(24), 4791-4800.
[http://dx.doi.org/10.1093/hmg/ddp442] [PMID: 19773341]
[58]
Edmondson, S.D.; Mastracchio, A.; Cox, J.M.; Eiermann, G.J.; He, H.; Lyons, K.A.; Patel, R.A.; Patel, S.B.; Petrov, A.; Scapin, G.; Wu, J.K.; Xu, S.; Zhu, B.; Thornberry, N.A.; Roy, R.S.; Weber, A.E. Aminopiperidine-fused imidazoles as dipeptidyl peptidase-IV inhibitors. Bioorg. Med. Chem. Lett., 2009, 19(15), 4097-4101.
[http://dx.doi.org/10.1016/j.bmcl.2009.06.011] [PMID: 19539471]
[59]
Mattei, P.; Boehringer, M.; Di Giorgio, P.; Fischer, H.; Hennig, M.; Huwyler, J.; Koçer, B.; Kuhn, B.; Loeffler, B.M.; Macdonald, A.; Narquizian, R.; Rauber, E.; Sebokova, E.; Sprecher, U. Discovery of carmegliptin: a potent and long-acting dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg. Med. Chem. Lett., 2010, 20(3), 1109-1113.
[http://dx.doi.org/10.1016/j.bmcl.2009.12.024] [PMID: 20031405]
[60]
Boehringer, M.; Fischer, H.; Hennig, M.; Hunziker, D.; Huwyler, J.; Kuhn, B.; Loeffler, B.M.; Luebbers, T.; Mattei, P.; Narquizian, R.; Sebokova, E.; Sprecher, U.; Wessel, H.P. Aryl- and heteroaryl-substituted aminobenzo[a]quinolizines as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2010, 20(3), 1106-1108.
[http://dx.doi.org/10.1016/j.bmcl.2009.12.025] [PMID: 20031408]
[61]
Meng, W.; Brigance, R.P.; Chao, H.J.; Fura, A.; Harrity, T.; Marcinkeviciene, J.; O’Connor, S.P.; Tamura, J.K.; Xie, D.; Zhang, Y.; Klei, H.E.; Kish, K.; Weigelt, C.A.; Turdi, H.; Wang, A.; Zahler, R.; Kirby, M.S.; Hamann, L.G. Discovery of 6-(aminomethyl)-5-(2,4-dichlorophenyl)-7-methylimidazo[1,2-a]pyrimidine-2-carboxamides as potent, selective dipeptidyl peptidase-4 (DPP4) inhibitors. J. Med. Chem., 2010, 53(15), 5620-5628.
[http://dx.doi.org/10.1021/jm100634a] [PMID: 20684603]
[62]
Wang, L.; Si, P.; Sheng, Y.; Chen, Y.; Wan, P.; Shen, X.; Tang, Y.; Chen, L.; Li, W. Discovery of new non-steroidal farnesoid X receptor modulators through 3D shape similarity search and structure-based virtual screening. Chem. Biol. Drug Des., 2015, 85(4), 481-487.
[http://dx.doi.org/10.1111/cbdd.12432] [PMID: 25228339]
[63]
Park, W.S. Discovery of b-aminoacyl containing thiazolidine derivatives as potent and selective dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2011, 21(5), 1366-1370.
[http://dx.doi.org/10.1016/j.bmcl.2011.01.041]
[64]
Liu, S.P. Crystal structure of dipeptidyl peptidase IV in complex with inhibitor, 2012.
[http://dx.doi.org/10.2210/pdb3QBJ/pdb]
[65]
Wang, W.; Devasthale, P.; Wang, A.; Harrity, T.; Egan, D.; Morgan, N.; Cap, M.; Fura, A.; Klei, H.E.; Kish, K.; Weigelt, C.; Sun, L.; Levesque, P.; Li, Y.X.; Zahler, R.; Kirby, M.S.; Hamann, L.G. 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site. Bioorg. Med. Chem. Lett., 2011, 21(22), 6646-6651.
[http://dx.doi.org/10.1016/j.bmcl.2011.09.074] [PMID: 21996520]
[66]
Yoshida, T.; Akahoshi, F.; Sakashita, H.; Kitajima, H.; Nakamura, M.; Sonda, S.; Takeuchi, M.; Tanaka, Y.; Ueda, N.; Sekiguchi, S.; Ishige, T.; Shima, K.; Nabeno, M.; Abe, Y.; Anabuki, J.; Soejima, A.; Yoshida, K.; Takashina, Y.; Ishii, S.; Kiuchi, S.; Fukuda, S.; Tsutsumiuchi, R.; Kosaka, K.; Murozono, T.; Nakamaru, Y.; Utsumi, H.; Masutomi, N.; Kishida, H.; Miyaguchi, I.; Hayashi, Y. Discovery and preclinical profile of teneligliptin (3-[(2S,4S)-4-[4-(3-methyl-1-phenyl-1H-pyrazol-5-yl)piperazin-1-yl]pyrrolidin-2-ylcarbonyl]thiazolidine): a highly potent, selective, long-lasting and orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. Bioorg. Med. Chem., 2012, 20(19), 5705-5719.
[http://dx.doi.org/10.1016/j.bmc.2012.08.012] [PMID: 22959556]
[67]
Yoshida, T.; Akahoshi, F.; Sakashita, H.; Sonda, S.; Takeuchi, M.; Tanaka, Y.; Nabeno, M.; Kishida, H.; Miyaguchi, I.; Hayashi, Y. Fused bicyclic heteroarylpiperazine-substituted L-prolylthiazo-lidines as highly potent DPP-4 inhibitors lacking the electrophilic nitrile group. Bioorg. Med. Chem., 2012, 20(16), 5033-5041.
[http://dx.doi.org/10.1016/j.bmc.2012.06.033] [PMID: 22824762]
[68]
Watanabe, Y.S.; Yasuda, Y.; Kojima, Y.; Okada, S.; Motoyama, T.; Takahashi, R.; Oka, M. Anagliptin, a potent dipeptidyl peptidase IV inhibitor: its single-crystal structure and enzyme interactions. J. Enzyme Inhib. Med. Chem., 2015, 30(6), 981-988.
[http://dx.doi.org/10.3109/14756366.2014.1002402] [PMID: 26147347]
[69]
Xiong, B. crystal structure of dpp-iv with compound c1, 2013.
[http://dx.doi.org/10.2210/pdb4DSA/pdb]
[70]
Xiong, B. crystal structure of dpp-iv with compound c2, 2013.
[http://dx.doi.org/10.2210/pdb4DSZ/pdb]
[71]
Xiong, B. crystal structure of dpp-iv with compound c5, 2013.
[http://dx.doi.org/10.2210/pdb4DTC/pdb]
[72]
Lam, B.; Zhang, Z.; Stafford, J.A.; Skene, R.J.; Shi, L.; Gwaltney, S.L. II Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(21), 6628-6631.
[http://dx.doi.org/10.1016/j.bmcl.2012.08.110] [PMID: 23025999]
[73]
Zhu, L.; Li, Y.; Qiu, L.; Su, M.; Wang, X.; Xia, C.; Qu, Y.; Li, J.; Li, J.; Xiong, B.; Shen, J. Design and synthesis of 4-(2,4,5-trifluorophenyl)butane-1,3-diamines as dipeptidyl peptidase IV inhibitors. ChemMedChem, 2013, 8(7), 1104-1116.
[http://dx.doi.org/10.1002/cmdc.201300104] [PMID: 23671024]
[74]
Devasthale, P.; Wang, Y.; Wang, W.; Fevig, J.; Feng, J.; Wang, A.; Harrity, T.; Egan, D.; Morgan, N.; Cap, M.; Fura, A.; Klei, H.E.; Kish, K.; Weigelt, C.; Sun, L.; Levesque, P.; Moulin, F.; Li, Y.X.; Zahler, R.; Kirby, M.S.; Hamann, L.G. Optimization of activity, selectivity, and liability profiles in 5-oxopyrrolopyridine DPP4 inhibitors leading to clinical candidate (Sa)-2-(3-(aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778). J. Med. Chem., 2013, 56(18), 7343-7357.
[http://dx.doi.org/10.1021/jm4008906] [PMID: 23964740]
[75]
Namoto, K.; Sirockin, F.; Ostermann, N.; Gessier, F.; Flohr, S.; Sedrani, R.; Gerhartz, B.; Trappe, J.; Hassiepen, U.; Duttaroy, A.; Ferreira, S.; Sutton, J.M.; Clark, D.E.; Fenton, G.; Beswick, M.; Baeschlin, D.K. Discovery of C-(1-aryl-cyclohexyl)-methylamines as selective, orally available inhibitors of dipeptidyl peptidase IV. Bioorg. Med. Chem. Lett., 2014, 24(3), 731-736.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.118] [PMID: 24439847]
[76]
Biftu, T.; Sinha-Roy, R.; Chen, P.; Qian, X.; Feng, D.; Kuethe, J.T.; Scapin, G.; Gao, Y.D.; Yan, Y.; Krueger, D.; Bak, A.; Eiermann, G.; He, J.; Cox, J.; Hicks, J.; Lyons, K.; He, H.; Salituro, G.; Tong, S.; Patel, S.; Doss, G.; Petrov, A.; Wu, J.; Xu, S.S.; Sewall, C.; Zhang, X.; Zhang, B.; Thornberry, N.A.; Weber, A.E. Omarigliptin (MK-3102): a novel long-acting DPP-4 inhibitor for once-weekly treatment of type 2 diabetes. J. Med. Chem., 2014, 57(8), 3205-3212.
[http://dx.doi.org/10.1021/jm401992e] [PMID: 24660890]
[77]
Xiao, P. Discovery of dipeptidyl peptidase IV (DPP4) inhibitors based on a novel indole scaffold. Chin. Chem. Lett., 2014, 25(5), 673-676.
[http://dx.doi.org/10.1016/j.cclet.2014.03.047]
[78]
Wu, W-L.; Hao, J.; Domalski, M.; Burnett, D.A.; Pissarnitski, D.; Zhao, Z.; Stamford, A.; Scapin, G.; Gao, Y.D.; Soriano, A.; Kelly, T.M.; Yao, Z.; Powles, M.A.; Chen, S.; Mei, H.; Hwa, J. Discovery of novel tricyclic heterocycles as potent and selective dpp-4 inhibitors for the treatment of type 2 diabetes. ACS Med. Chem. Lett., 2016, 7(5), 498-501.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00027] [PMID: 27190600]
[79]
Cox, J.M.; Chu, H.D.; Kuethe, J.T.; Gao, Y.D.; Scapin, G.; Eiermann, G.; He, H.; Li, X.; Lyons, K.A.; Metzger, J.; Petrov, A.; Wu, J.K.; Xu, S.; Sinha-Roy, R.; Weber, A.E.; Biftu, T. The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors. Bioorg. Med. Chem. Lett., 2016, 26(11), 2622-2626.
[http://dx.doi.org/10.1016/j.bmcl.2016.04.020] [PMID: 27106708]
[80]
Grimshaw, C.E.; Jennings, A.; Kamran, R.; Ueno, H.; Nishigaki, N.; Kosaka, T.; Tani, A.; Sano, H.; Kinugawa, Y.; Koumura, E.; Shi, L.; Takeuchi, K. Trelagliptin (SYR-472, Zafatek), novel once-weekly treatment for type 2 diabetes, inhibits dipeptidyl peptidase-4 (dpp-4) via a non-covalent mechanism. PLoS One, 2016, 11(6) e0157509
[http://dx.doi.org/10.1371/journal.pone.0157509] [PMID: 27328054]
[81]
Pissarnitski, D.A.; Zhao, Z.; Cole, D.; Wu, W.L.; Domalski, M.; Clader, J.W.; Scapin, G.; Voigt, J.; Soriano, A.; Kelly, T.; Powles, M.A.; Yao, Z.; Burnett, D.A. Scaffold-hopping from xanthines to tricyclic guanines: A case study of dipeptidyl peptidase 4 (DPP4) inhibitors. Bioorg. Med. Chem., 2016, 24(21), 5534-5545.
[http://dx.doi.org/10.1016/j.bmc.2016.09.007] [PMID: 27670099]
[82]
Berger, J.P. SinhaRoy, R.; Pocai, A.; Kelly, T.M.; Scapin, G.; Gao, Y.D.; Pryor, K.A.D.; Wu, J.K.; Eiermann, G.J.; Xu, S.S.; Zhang, X.; Tatosian, D.A.; Weber, A.E.; Thornberry, N.A.; Carr, R.D. A comparative study of the binding properties, dipeptidyl peptidase-4 (DPP-4) inhibitory activity and glucose-lowering efficacy of the DPP-4 inhibitors alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin in mice. Endocrinol. Diab. Metab., 2017, 1(1) e00002
[http://dx.doi.org/10.1002/edm2.2] [PMID: 30815539]
[83]
Morris, G.M.; Huey, R.; Lindstrom, W.; Sanner, M.F.; Belew, R.K.; Goodsell, D.S.; Olson, A.J. AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. J. Comput. Chem., 2009, 30(16), 2785-2791.
[http://dx.doi.org/10.1002/jcc.21256] [PMID: 19399780]
[84]
DeLano, W.L. The Pymol Molecular Grafics System; Schrödinger: New York, 2002.
[85]
Shan, J.; Ji, C. MolOpt: A web server for drug design using bioisosteric transformation. Curr. Computer-Aided Drug Des., 2019. (in press)
[http://dx.doi.org/10.2174/1573409915666190704093400]
[86]
Meanwell, N.A. Synopsis of some recent tactical application of bioisosteres in drug design. J. Med. Chem., 2011, 54(8), 2529-2591.
[http://dx.doi.org/10.1021/jm1013693] [PMID: 21413808]
[87]
Daina, A.; Michielin, O.; Zoete, V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci. Rep., 2017, 7, 42717-42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[88]
Daina, A.; Michielin, O.; Zoete, V. iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. J. Chem. Inf. Model., 2014, 54(12), 3284-3301.
[http://dx.doi.org/10.1021/ci500467k] [PMID: 25382374]
[89]
Daina, A.; Zoete, V. A BOILED-Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules. ChemMedChem, 2016, 11(11), 1117-1121.
[http://dx.doi.org/10.1002/cmdc.201600182] [PMID: 27218427]
[90]
Pires, D.E.V.; Blundell, T.L.; Ascher, D.B. pkCSM: Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures. J. Med. Chem., 2015, 58(9), 4066-4072.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00104] [PMID: 25860834]
[91]
Ji, C.; Svensson, F.; Zoufir, A.; Bender, A. eMolTox: prediction of molecular toxicity with confidence. Bioinformatics, 2018, 34(14), 2508-2509.
[http://dx.doi.org/10.1093/bioinformatics/bty135] [PMID: 29522123]
[92]
Stierand, K.; Maass, P.C.; Rarey, M. Molecular complexes at a glance: automated generation of two-dimensional complex diagrams. Bioinformatics, 2006, 22(14), 1710-1716.
[http://dx.doi.org/10.1093/bioinformatics/btl150] [PMID: 16632493]
[93]
Clark, R.D.; Fox, P.C. Statistical variation in progressive scrambling. J. Comput. Aided Mol. Des., 2004, 18(7-9), 563-576.
[http://dx.doi.org/10.1007/s10822-004-4077-z] [PMID: 15729855]
[94]
Pires, D.E.V.; Kaminskas, L.M.; Ascher, D.B. Prediction and Optimization of Pharmacokinetic and Toxicity Properties of the Ligand. In: Computational Drug Discovery and Design, Methods in Molecular Biology; Springer Science+Business Media, LLC: Berlin, 2018; Volume 1762, pp. 271-284.
[http://dx.doi.org/10.1007/978-1-4939-7756-7_14]
[95]
El Kerdawy, A.M.; Osman, A.A.; Zaater, M.A. Receptor-based pharmacophore modeling, virtual screening, and molecular docking studies for the discovery of novel GSK-3β inhibitors. J. Mol. Model., 2019, 25(6), 171.
[http://dx.doi.org/10.1007/s00894-019-4032-5] [PMID: 31129879]
[96]
Ramya, K.S.; Iqbal, S.; Gunasekaran, K.; Radha, A. Anticancer potentials of quassinoids from simarouba glauca - docking and ADME analysis. RJLSBPCS, 2018, 4(5), 218.
[97]
Maezaki, H.; Tawada, M.; Yamashita, T.; Banno, Y.; Miyamoto, Y.; Yamamoto, Y.; Ikedo, K.; Kosaka, T.; Tsubotani, S.; Tani, A.; Asakawa, T.; Suzuki, N.; Oi, S. Design of potent dipeptidyl peptidase IV (DPP-4) inhibitors by employing a strategy to form a salt bridge with Lys554. Bioorg. Med. Chem. Lett., 2017, 27(15), 3565-3571.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.048] [PMID: 28579121]
[98]
Patel, B.D.; Ghate, M.D. 3D-QSAR studies of dipeptidyl peptidase-4 inhibitors using various alignment methods. Med. Chem. Res., 2015, 24, 1060-1069.
[http://dx.doi.org/10.1007/s00044-014-1178-7]
[99]
Oi, S.; Maezaki, H.; Ikedou, K. Preparation of fused heterocyclic compounds as peptidase inhibitors. Patent WO2004014860. 2004.
[100]
Clayden, J. Organic Chemistry; Oxford University Press: Oxford, UK, 2000.
[101]
Wright, A.J. The penicillins. Mayo Clin. Proc., 1999, 74(3), 290-307.
[http://dx.doi.org/10.4065/74.3.290] [PMID: 10090000]
[102]
Singh, G.S. Emerging trends in chemistry and pharmacology of β-lactams. Mod. Chem. App., 2013, 1 e108
[http://dx.doi.org/10.4172/2329-6798.1000e108]
[103]
Bhusnure, O.G. Microwave assisted and conventional synthesis, characterization and biological activity of 2-azetidinones and 4-thiazolidinone. J. Pharm. Biomed. Sci., 2011, 6, 1-8.
[104]
Basavaraj, K.; Asifiqbal, K. Synthesis, docking and antitubercular activity of some newer azetidinones. Unique. J. Pharm. Biol. Sci., 2014, 2, 43-50.
[105]
Chavan, A.A.; Pai, N.R. Synthesis and biological activity of N-substituted-3-chloro-2-azetidinones. Molecules, 2007, 12(11), 2467-2477.
[http://dx.doi.org/10.3390/12112467] [PMID: 18065951]
[106]
Nimbalkar, U.D.; Seijas, J.A.; Borkute, R.; Damale, M.G.; Sangshetti, J.N.; Sarkar, D.; Nikalje, A.P.G. Ultrasound assisted synthesis of 4-(Benzyloxy)-N-(3-chloro-2-(substitutedphenyl)-4-oxoazetidin-1-yl) benzamide as challenging anti-tubercular scaffold. Molecules, 2018, 23(8), 1945-1964.
[http://dx.doi.org/10.3390/molecules23081945] [PMID: 30081525]

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