Current Medicinal ChemistryCurrent Medicinal ChemistryCurrent Medicinal Chemistry0929-86731875-533XBentham Science64516010.2174/0929867330666230426111650Anti-Infectives and Infectious DiseasesResearch ArticleImidazo[4,5-b]Pyridines: From Kinase Inhibitors to more Diversified Biological PropertiesJarmoniKariminfo@benthamscience.netMisbahiKhalidinfo@benthamscience.netFerrièresVincentinfo@benthamscience.net, Univ Rennes, Ecole Nationale Supérieure de Chimie de RennesLaboratoire de Chimie Organique Appliquée, Faculté des Sciences et Techniques, Université Sidi Mohammed Ben Abdalla0102202431551552807012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://rjraap.com/0929-8673/article/view/645160

Imidazo[4,5-b]pyridines are amongst the oldest known heteroaromatic derivatives. Their structural similarity with purine basis has however aroused the curiosity of biologists and resulted in the developments of innovative bioactive compounds. This review thus firstly describes the main synthetic ways currently used to produce imidazo[ 4,5-b]pyridine derivatives, and secondly gives examples of their potential, especially focusing on protein inhibition abilities, thus opening the way to applications as anti-cancer or antimicrobial agents.

Imidazo[4,5-b]pyridinessynthesiskinase inhibitorsantimicrobial activitiesantioxidant propertiesheteroaromatic derivatives.Foster, A.; Kemp, J. Glutamate- and GABA-based CNS therapeutics. Curr. Opin. Pharmacol., 2006, 6(1), 7-17. doi: 10.1016/j.coph.2005.11.005 PMID: 16377242Temple, C., Jr; Rose, J.D.; Comber, R.N.; Rener, G.A. Synthesis of potential anticancer agents: Imidazo4,5-cpyridines and imidazo4,5-bpyridines. J. Med. Chem., 1987, 30(10), 1746-1751. doi: 10.1021/jm00393a011 PMID: 3656351Cristalli, G.; Vittori, S.; Eleuteri, A.; Grifantini, M.; Volpini, R.; Lupidi, G.; Capolongo, L.; Pesenti, E. Purine and 1-deazapurine ribonucleosides and deoxyribonucleosides: Synthesis and biological activity. J. Med. Chem., 1991, 34(7), 2226-2230. doi: 10.1021/jm00111a044 PMID: 2066996Cristalli, G.; Vittori, S.; Eleuteri, A.; Volpini, R.; Camaioni, E.; Lupidi, G.; Mahmood, N.; Bevilacqua, F.; Palù, G. Synthesis and biological evaluation of N6-cycloalkyl derivatives of 1-deazaadenine nucleosides: A new class of anti-human immunodeficiency virus agents. J. Med. Chem., 1995, 38(20), 4019-4025. doi: 10.1021/jm00020a017 PMID: 7562937Cundy, D.J.; Holan, G.; Otaegui, M.; Simpson, G.W. 3-(3′-Hydroxymethyl)-4′-hydroxybutylimidazo4,5-b pyridines-novel antiviral agents. Bioorg. Med. Chem. Lett., 1997, 7(6), 669-674. doi: 10.1016/S0960-894X(97)00082-6Banie, H.; Sinha, A.; Thomas, R.J.; Sircar, J.C.; Richards, M.L. 2-phenylimidazopyridines, a new series of Golgi compounds with potent antiviral activity. J. Med. Chem., 2007, 50(24), 5984-5993. doi: 10.1021/jm0704907 PMID: 17973358Mader, M.; de Dios, A.; Shih, C.; Bonjouklian, R.; Li, T.; White, W.; de Uralde, B.L.; Sánchez-Martinez, C.; del Prado, M.; Jaramillo, C.; de Diego, E.; Martín Cabrejas, L.M.; Dominguez, C.; Montero, C.; Shepherd, T.; Dally, R.; Toth, J.E.; Chatterjee, A.; Pleite, S.; Blanco-Urgoiti, J.; Perez, L.; Barberis, M.; Lorite, M.J.; Jambrina, E.; Nevill, C.R., Jr; Lee, P.A.; Schultz, R.C.; Wolos, J.A.; Li, L.C.; Campbell, R.M.; Anderson, B.D. Imidazolyl benzimidazoles and imidazo4,5-bpyridines as potent p38α MAP kinase inhibitors with excellent in vivo antiinflammatory properties. Bioorg. Med. Chem. Lett., 2008, 18(1), 179-183. doi: 10.1016/j.bmcl.2007.10.106 PMID: 18039577Bukowski, L.; Kaliszan, R. Imidazo4,5-bpyridine derivatives of potential tuberculostatic activity. Part 1: Synthesis and quantitative structure-activity relationships. Arch. Pharm. (Weinheim), 1991, 324(2), 121-127. doi: 10.1002/ardp.19913240212 PMID: 1906702Nicholson, A.N.; Pascoe, P.A. Hypnotic activity of an imidazo-pyridine (zolpidem). Br. J. Clin. Pharmacol., 1986, 21(2), 205-211. doi: 10.1111/j.1365-2125.1986.tb05176.x PMID: 3954937Holm, K.J.; Goa, K.L. Zolpidem. Drugs, 2000, 59(4), 865-889. doi: 10.2165/00003495-200059040-00014 PMID: 10804040Bolm, C.; Hendriks, C.; Nürnberg, P. Zolimidine analogues: The synthesis of imidazo1,2-αpyridine-based sulfilimines and sulfoximines. Synthesis, 2015, 47(8), 1190-1194. doi: 10.1055/s-0034-1380109Bagdi, A.K.; Santra, S.; Monir, K.; Hajra, A. Synthesis of imidazo1,2-apyridines: A decade update. Chem. Commun., 2015, 51(9), 1555-1575. doi: 10.1039/C4CC08495K PMID: 25407981Krause, M.; Foks, H.; Gobis, K. Pharmacological potential and synthetic approaches of imidazo4,5-bpyridine and imidazo4,5-cpyridine derivatives. Molecules, 2017, 22(3), 399. doi: 10.3390/molecules22030399 PMID: 28273868Tschitschibabin, A.E.; Kirsanow, A.W. α, β′-Diamino-pyridin und α, β-Diamino-pyridin. Ber. Dtsch. Chem. Ges. B, 1927, 60(3), 766-776. doi: 10.1002/cber.19270600330Dymińska, L.; Gągor, A.; Talik, Z.; Lorenc, J.; Hanuza, J. Vibrational spectra and structure of methyl-derivatives of imidazo4,5-cpyridine based on DFT quantum chemical calculations and XRD studies. Vib. Spectrosc., 2011, 57(2), 229-241. doi: 10.1016/j.vibspec.2011.07.009René, O.; Souverneva, A.; Magnuson, S.R.; Fauber, B.P. Efficient syntheses of 2-fluoroalkylbenzimidazoles and -benzothiazoles. Tetrahedron Lett., 2013, 54(3), 201-204. doi: 10.1016/j.tetlet.2012.09.069Baladi, T.; Aziz, J.; Dufour, F.; Abet, V.; Stoven, V.; Radvanyi, F.; Poyer, F.; Wu, T.D.; Guerquin-Kern, J.L.; Bernard-Pierrot, I.; Garrido, S.M.; Piguel, S. Design, synthesis, biological evaluation and cellular imaging of imidazo4,5-bpyridine derivatives as potent and selective TAM inhibitors. Bioorg. Med. Chem., 2018, 26(20), 5510-5530. doi: 10.1016/j.bmc.2018.09.031 PMID: 30309671Kale, R.P.; Shaikh, M.U.; Jadhav, G.R.; Gill, C.H. Eco-friendly and facile synthesis of 2-substituted-1H-imidazo4,5-bpyridine in aqueous medium by air oxidation. Tetrahedron Lett., 2009, 50(16), 1780-1782. doi: 10.1016/j.tetlet.2008.12.104Dekhane, D.V.; Pawar, S.S.; Gupta, S.V.; Shingare, M.S.; Thore, S.N. Lithium bromide catalyzed solvent free method for synthesis of 2-substituted benzimidazoles and imidazopyridines. Chin. Chem. Lett., 2010, 21(5), 519-523. doi: 10.1016/j.cclet.2009.11.034Joule, J.A.; Mills, K. Heterocyclic Chemistry, 4th ed; Blackwell Publishing: India, 2007.Hranjec, M.; Lučić, B.; Ratkaj, I.; Pavelić, S.K.; Piantanida, I.; Pavelić, K.; Karminski-Zamola, G. Novel imidazo4,5-bpyridine and triaza-benzocfluorene derivatives: Synthesis, antiproliferative activity and DNA binding studies. Eur. J. Med. Chem., 2011, 46(7), 2748-2758. doi: 10.1016/j.ejmech.2011.03.062 PMID: 21524829Hranjec, M.; Pavlović, G.; Marinović, M.; Karminski-Zamola, G. Synthesis, spectroscopic properties and crystal structure determination of 2-(2-pyridin-4-yl-vinyl)-1H-benzimidazole derivatives. Struct. Chem., 2008, 19(2), 353-359. doi: 10.1007/s11224-008-9291-1Kappe, C. O.; Dallinger, D.; Murphree, S. S. Practical Microwave Synthesis for Organic Chemists: Strategies, Instruments, and Protocols. 2008. p. 525. doi: 10.1002/9783527623907Martínez-Palou, R.; Zepeda, L.G.; Höpfl, H.; Montoya, A.; Guzmán-Lucero, D.J.; Guzmán, J. Parallel and automated library synthesis of 2-long alkyl chain benzoazoles and azole4,5-bpyridines under microwave irradiation. Mol. Divers., 2005, 9(4), 361-369. doi: 10.1007/s11030-005-6357-5 PMID: 16311813Bavetsias, V.; Large, J.M.; Sun, C.; Bouloc, N.; Kosmopoulou, M.; Matteucci, M.; Wilsher, N.E.; Martins, V.; Reynisson, J.; Atrash, B.; Faisal, A.; Urban, F.; Valenti, M.; de Haven Brandon, A.; Box, G.; Raynaud, F.I.; Workman, P.; Eccles, S.A.; Bayliss, R.; Blagg, J.; Linardopoulos, S.; McDonald, E. Imidazo4,5-bpyridine derivatives as inhibitors of Aurora kinases: Lead optimization studies toward the identification of an orally bioavailable preclinical development candidate. J. Med. Chem., 2010, 53(14), 5213-5228. doi: 10.1021/jm100262j PMID: 20565112Bourichi, S.; Rodi, Y.K.; Hoekelek, T.; Ouzidan, Y.; Chahdi, F.O.; Akhazzane, M.; Essassi, E.M. Crystal structure and Hirshfeld surface analysis of 6-bromo-2-(4-chlorophenyl)-3-((1-octyl-1H-1,2,3-triazol-4-yl)methyl)-3H-imidazo4,5-Bpyridine. J. Maroc. Chim. Heterocycl., 2019, 18(1), 43.Jabri, Z.; Sebbar, N.K.; Hökelek, T.; Mague, J.T.; Sabir, S.; Rodi, Y.K.; Misbahi, K. Crystal structure, Hirshfeld surface analysis and DFT study of 6-bromo-3-(5-bromohexyl)-2-4-(dimethylamino)-phenyl-3H-imidazo4,5-bpyridine. Acta Crystallogr. Sect. E Struct. Rep. Online, 2020, E76, 1234.Jabri, Z.; Ibrahimi, B.E.; Jarmoni, K.; Sabir, S.; Misbahi, K.; Rodi, Y.K.; Mashrai, A.; Hökelek, T.; Mague, J.T.; Sebbar, N.K. New imidazo4,5-bpyridine derivatives: Synthesis, crystal structures, Hirshfeld surface analysis, DFT computations and Monte Carlo simulations. J. Chem. Technol. Metal., 2022, 57(3), 451.Salomé, C.; Schmitt, M.; Bourguignon, J.J. Rapid synthesis of imidazo4,5-bpyridine containing polycyclics by means of palladium-catalyzed amidation of 2-chloro-3-nitropyridine. Tetrahedron Lett., 2009, 50(27), 3798-3800. doi: 10.1016/j.tetlet.2009.04.031Chen, G.; Liu, Z.; Zhang, Y.; Shan, X.; Jiang, L.; Zhao, Y.; He, W.; Feng, Z.; Yang, S.; Liang, G. Synthesis and anti-inflammatory evaluation of novel benzimidazole and imidazopyridine derivatives. ACS Med. Chem. Lett., 2013, 4(1), 69-74. doi: 10.1021/ml300282t PMID: 24900565Shin, J.M.; Homerin, M.; Domagala, F.; Ficheux, H.; Sachs, G. Characterization of the inhibitory activity of tenatoprazole on the gastric H+,K+-ATPase in vitro and in vivo. Biochem. Pharmacol., 2006, 71(6), 837-849. doi: 10.1016/j.bcp.2005.11.030 PMID: 16405921Scarpignato, C.; Hunt, R. Proton pump inhibitors: The beginning of the end or the end of the beginning? Curr. Opin. Pharmacol., 2008, 8(6), 677-684. doi: 10.1016/j.coph.2008.09.004 PMID: 18840545Shin, J.M.; Cho, Y.M.; Sachs, G. Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors. J. Am. Chem. Soc., 2004, 126(25), 7800-7811. doi: 10.1021/ja049607w PMID: 15212527Hall, P.A.; Levison, D.A. Review: Assessment of cell proliferation in histological material. J. Clin. Pathol., 1990, 43(3), 184-192. doi: 10.1136/jcp.43.3.184 PMID: 2185282Manning, B.D.; Cantley, L.C. AKT/PKB signaling: Navigating downstream. Cell, 2007, 129(7), 1261-1274. doi: 10.1016/j.cell.2007.06.009 PMID: 17604717Manning, B.D.; Toker, A. AKT/PKB signaling: Navigating the network. Cell, 2017, 169(3), 381-405. doi: 10.1016/j.cell.2017.04.001 PMID: 28431241Matheny, R.W., Jr; Adamo, M.L. Current perspectives on AKT Activation and AKT-ions. Exp. Biol. Med., 2009, 234(11), 1264-1270. doi: 10.3181/0904-MR-138 PMID: 19596822Song, M.; Bode, A.M.; Dong, Z.; Lee, M.H. AKT as a therapeutic target for cancer. Cancer Res., 2019, 79(6), 1019-1031. doi: 10.1158/0008-5472.CAN-18-2738 PMID: 30808672Hinz, N.; Jücker, M. Distinct functions of AKT isoforms in breast cancer: A comprehensive review. Cell Commun. Signal., 2019, 17(1), 154. doi: 10.1186/s12964-019-0450-3 PMID: 31752925Pascual, J.; Turner, N.C. Targeting the PI3-kinase pathway in triple-negative breast cancer. Ann. Oncol., 2019, 30(7), 1051-1060. doi: 10.1093/annonc/mdz133 PMID: 31050709Ashwell, M.A.; Lapierre, J.M.; Brassard, C.; Bresciano, K.; Bull, C.; Cornell-Kennon, S.; Eathiraj, S.; France, D.S.; Hall, T.; Hill, J.; Kelleher, E.; Khanapurkar, S.; Kizer, D.; Koerner, S.; Link, J.; Liu, Y.; Makhija, S.; Moussa, M.; Namdev, N.; Nguyen, K.; Nicewonger, R.; Palma, R.; Szwaya, J.; Tandon, M.; Uppalapati, U.; Vensel, D.; Volak, L.P.; Volckova, E.; Westlund, N.; Wu, H.; Yang, R.Y.; Chan, T.C.K. Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo4,5-bpyridin-2-yl)pyridin-2-amines: Orally bioavailable, selective, and potent ATP-independent Akt inhibitors. J. Med. Chem., 2012, 55(11), 5291-5310. doi: 10.1021/jm300276x PMID: 22533986Hallberg, B.; Palmer, R.H. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat. Rev. Cancer, 2013, 13(10), 685-700. doi: 10.1038/nrc3580 PMID: 24060861Learn, K.S.; Wagner, J.C.; Albom, M.S.; Angeles, T.S.; Huang, Z.; Ghose, A.K.; Wan, W.; Cheng, M.; Dorsey, B.D.; Ott, G.R. Design of 7-amino-6-chloro-3H-imidazo4,5-bpyridine scaffold from 5-chloro-2,4-diaminopyrimidine pharmacophore: Identification of potent inhibitors of anaplastic lymphoma kinase. MedChemComm, 2012, 3(9), 1138. doi: 10.1039/c2md20061aGschwind, A.; Fischer, O.M.; Ullrich, A. The discovery of receptor tyrosine kinases: Targets for cancer therapy. Nat. Rev. Cancer, 2004, 4(5), 361-370. doi: 10.1038/nrc1360 PMID: 15122207Wiesmann, C.; Ultsch, M.H.; Bass, S.H.; de Vos, A.M. Crystal structure of nerve growth factor in complex with the ligand-binding domain of the TrkA receptor. Nature, 1999, 401(6749), 184-188. doi: 10.1038/43705 PMID: 10490030Wang, T.; Lamb, M.L.; Block, M.H.; Davies, A.M.; Han, Y.; Hoffmann, E.; Ioannidis, S.; Josey, J.A.; Liu, Z.Y.; Lyne, P.D.; MacIntyre, T.; Mohr, P.J.; Omer, C.A.; Sjögren, T.; Thress, K.; Wang, B.; Wang, H.; Yu, D.; Zhang, H.J. Discovery of disubstituted imidazo4,5- b pyridines and purines as potent TrkA inhibitors. ACS Med. Chem. Lett., 2012, 3(9), 705-709. doi: 10.1021/ml300074j PMID: 24900538Thress, K.; MacIntyre, T.; Wang, H.; Whitston, D.; Liu, Z.Y.; Hoffmann, E.; Wang, T.; Brown, J.L.; Webster, K.; Omer, C.; Zage, P.E.; Zeng, L.; Zweidler-McKay, P.A. Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Mol. Cancer Ther., 2009, 8(7), 1818-1827. doi: 10.1158/1535-7163.MCT-09-0036 PMID: 19509272Bavetsias, V.; Sun, C.; Bouloc, N.; Reynisson, J.; Workman, P.; Linardopoulos, S.; McDonald, E. Hit generation and exploration: Imidazo4,5-bpyridine derivatives as inhibitors of Aurora kinases. Bioorg. Med. Chem. Lett., 2007, 17(23), 6567-6571. doi: 10.1016/j.bmcl.2007.09.076 PMID: 17933533Carvajal, R.D.; Tse, A.; Schwartz, G.K. Aurora kinases: New targets for cancer therapy. Clin. Cancer Res., 2006, 12(23), 6869-6875. doi: 10.1158/1078-0432.CCR-06-1405 PMID: 17145803Bolanos-Garcia, V.M. Aurora kinases. Int. J. Biochem. Cell Biol., 2005, 37(8), 1572-1577. doi: 10.1016/j.biocel.2005.02.021 PMID: 15896667Keen, N.; Taylor, S. Aurora-kinase inhibitors as anticancer agents. Nat. Rev. Cancer, 2004, 4(12), 927-936. doi: 10.1038/nrc1502 PMID: 15573114Becker, W.; Sippl, W. Activation, regulation, and inhibition of DYRK1A. FEBS J., 2011, 278(2), 246-256. doi: 10.1111/j.1742-4658.2010.07956.x PMID: 21126318Jarhad, D.B.; Mashelkar, K.K.; Kim, H.R.; Noh, M.; Jeong, L.S. Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitors as potential therapeutics. J. Med. Chem., 2018, 61(22), 9791-9810. doi: 10.1021/acs.jmedchem.8b00185 PMID: 29985601Weber, C.; Sipos, M.; Paczal, A.; Balint, B.; Kun, V.; Foloppe, N.; Dokurno, P.; Massey, A.J.; Walmsley, D.L.; Hubbard, R.E.; Murray, J.; Benwell, K.; Edmonds, T.; Demarles, D.; Bruno, A.; Burbridge, M.; Cruzalegui, F.; Kotschy, A. Structure-guided discovery of potent and selective DYRK1A inhibitors. J. Med. Chem., 2021, 64(10), 6745-6764. doi: 10.1021/acs.jmedchem.1c00023 PMID: 33975430WHO. Neurological Disorders: Public Health Challenges. https://www.who.int/publications/i/item/97892415633692022.Medina, M.; Avila, J. Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer’s disease. Curr. Pharm. Des., 2010, 16(25), 2790-2798. doi: 10.2174/138161210793176581 PMID: 20698823Hooper, C.; Killick, R.; Lovestone, S. The GSK3 hypothesis of Alzheimer’s disease. J. Neurochem., 2008, 104(6), 1433-1439. doi: 10.1111/j.1471-4159.2007.05194.x PMID: 18088381Sharma, N.; Singh, A.N. Exploring biomarkers for Alzheimer’s disease. J. Clin. Diagn. Res., 2016, 10(7), KE01-KE06. PMID: 27630867Mantzavinos, V.; Alexiou, A. Biomarkers for Alzheimer’s disease diagnosis. Curr. Alzheimer Res., 2017, 14(11), 1149-1154. PMID: 28164766Humpel, C. Identifying and validating biomarkers for Alzheimer’s disease. Trends Biotechnol., 2011, 29(1), 26-32. doi: 10.1016/j.tibtech.2010.09.007 PMID: 20971518Lee, S.C.; Kim, H.T.; Park, C.H.; Lee, D.Y.; Chang, H.J.; Park, S.; Cho, J.M.; Ro, S.; Suh, Y.G. Design, synthesis and biological evaluation of novel imidazopyridines as potential antidiabetic GSK3β inhibitors. Bioorg. Med. Chem. Lett., 2012, 22(13), 4221-4224. doi: 10.1016/j.bmcl.2012.05.060 PMID: 22672803Pearson, G.; Robinson, F.; Beers Gibson, T.; Xu, B.E.; Karandikar, M.; Berman, K.; Cobb, M.H. Mitogen-activated protein (MAP) kinase pathways: Regulation and physiological functions. Endocr. Rev., 2001, 22(2), 153-183. PMID: 11294822Peyssonnaux, C.; Eychène, A. The Raf/MEK/ERK pathway: New concepts of activation. Biol. Cell, 2001, 93(1-2), 53-62. doi: 10.1016/S0248-4900(01)01125-X PMID: 11730323Newhouse, B.J.; Wenglowsky, S.; Grina, J.; Laird, E.R.; Voegtli, W.C.; Ren, L.; Ahrendt, K.; Buckmelter, A.; Gloor, S.L.; Klopfenstein, N.; Rudolph, J.; Wen, Z.; Li, X.; Feng, B. Imidazo4,5-bpyridine inhibitors of B-Raf kinase. Bioorg. Med. Chem. Lett., 2013, 23(21), 5896-5899. doi: 10.1016/j.bmcl.2013.08.086 PMID: 24042006An, X.D.; Liu, H.; Xu, Z.L.; Jin, Y.; Peng, X.; Yao, Y.M.; Geng, M.; Long, Y.Q. Discovery of potent 1H-imidazo4,5-bpyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization. Bioorg. Med. Chem. Lett., 2015, 25(3), 708-716. doi: 10.1016/j.bmcl.2014.11.070 PMID: 25529740Organ, S.L.; Tsao, M.S. An overview of the c-MET signaling pathway. Ther. Adv. Med. Oncol., 2011, 3(1_suppl)(Suppl.), S7-S19. doi: 10.1177/1758834011422556 PMID: 22128289Chen, D.; Wang, Y.; Ma, Y.; Xiong, B.; Ai, J.; Chen, Y.; Geng, M.; Shen, J. Discovery of 3H-imidazo4,5-bpyridines as potent c-Met kinase inhibitors: Design, synthesis, and biological evaluation. ChemMedChem, 2012, 7(6), 1057-1070. doi: 10.1002/cmdc.201200120 PMID: 22581753Park, J. K.; Kim, S.; Han, Y. J.; Kim, S. H.; Kang, N. S.; Lee, H.; Park, S. The discovery and the structural basis of an imidazo4,5-bpyridine-based p21-activated kinase 4 inhibitor. Bioorg Med. Chem. Lett., 2016, 26(11), 2580-2583.Ye, D.Z.; Field, J. PAK signaling in cancer. Cell. Logist., 2012, 2(2), 105-116. doi: 10.4161/cl.21882 PMID: 23162742Sivilotti, L.; Nistri, A. GABA receptor mechanisms in the central nervous system. Prog. Neurobiol., 1991, 36(1), 35-92. doi: 10.1016/0301-0082(91)90036-Z PMID: 1847747Watanabe, M.; Maemura, K.; Kanbara, K.; Tamayama, T.; Hayasaki, H. GABA and GABA receptors in the central nervous system and other organs. Int. Rev. Cytol., 2002, 213, 1-47. doi: 10.1016/S0074-7696(02)13011-7 PMID: 11837891Bormann, J. The ‘ABC’ of GABA receptors. Trends Pharmacol. Sci., 2000, 21(1), 16-19. doi: 10.1016/S0165-6147(99)01413-3 PMID: 10637650Larsen, J.S.; Amrutkar, D.; Jacobsen, T.A.; Dyhring, T.; Nielsen, K.S.A. GABAA receptor ligand. Int. Patent, 2020, WO2020(053377), A1.Menniti, F.S.; Faraci, W.S.; Schmidt, C.J. Phosphodiesterases in the CNS: Targets for drug development. Nat. Rev. Drug Discov., 2006, 5(8), 660-670. doi: 10.1038/nrd2058 PMID: 16883304Siuciak, J.A.; Chapin, D.S.; Harms, J.F.; Lebel, L.A.; McCarthy, S.A.; Chambers, L.; Shrikhande, A.; Wong, S.; Menniti, F.S.; Schmidt, C.J. Inhibition of the striatum-enriched phosphodiesterase PDE10A: A novel approach to the treatment of psychosis. Neuropharmacology, 2006, 51(2), 386-396. doi: 10.1016/j.neuropharm.2006.04.013 PMID: 16780899Seeger, T.F.; Bartlett, B.; Coskran, T.M.; Culp, J.S.; James, L.C.; Krull, D.L.; Lanfear, J.; Ryan, A.M.; Schmidt, C.J.; Strick, C.A.; Varghese, A.H.; Williams, R.D.; Wylie, P.G.; Menniti, F.S. Immunohistochemical localization of PDE10A in the rat brain. Brain Res., 2003, 985(2), 113-126. doi: 10.1016/S0006-8993(03)02754-9 PMID: 12967715Hu, E.; Kunz, R.K.; Chen, N.; Rumfelt, S.; Siegmund, A.; Andrews, K.; Chmait, S.; Zhao, S.; Davis, C.; Chen, H.; Lester-Zeiner, D.; Ma, J.; Biorn, C.; Shi, J.; Porter, A.; Treanor, J.; Allen, J.R. Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A). J. Med. Chem., 2013, 56(21), 8781-8792. doi: 10.1021/jm401234w PMID: 24102193Lucas, J.A.; Hawkins, N.J.; Fraaije, B.A. The evolution of fungicide resistance. Adv. Appl. Microbiol., 2015, 90, 29-92. doi: 10.1016/bs.aambs.2014.09.001 PMID: 25596029Wu, D.; Liu, M.; Li, Z.; Dang, M.; Liu, X.; Li, J.; Huang, L.; Ren, Y.; Zhang, Z.; Liu, W.; Liu, A. Synthesis and fungicidal activity of novel imidazo4,5-bpyridine derivatives. Heterocycl. Commun., 2019, 25(1), 8-14. doi: 10.1515/hc-2019-0003Liu, M.; Quan, C.; Dang, M.; Ren, Y.; Ren, J.; Xiang, J.; Liu, X.; He, L.; Liu, W.; Liu, A. Design, synthesis, and activity of novel i4,5-bpyridine derivatives. J. Heterocycl. Chem., 2018, 55(9), 2061-2068. doi: 10.1002/jhet.3243Lukasik, P.M.; Elabar, S.; Lam, F.; Shao, H.; Liu, X.; Abbas, A.Y.; Wang, S. Synthesis and biological evaluation of imidazo4,5-bpyridine and 4-heteroaryl-pyrimidine derivatives as anti-cancer agents. Eur. J. Med. Chem., 2012, 57, 311-322. doi: 10.1016/j.ejmech.2012.09.034 PMID: 23085105Sudre, P.; ten Dam, G.; Kochi, A. Tuberculosis: A global overview of the situation today. Bull. World Health Organ., 1992, 70(2), 149-159. PMID: 1600578Gawad, J.; Bonde, C. Synthesis, biological evaluation and molecular docking studies of 6-(4-nitrophenoxy)-1H-imidazo4,5-bpyridine derivatives as novel antitubercular agents: Future DprE1 inhibitors. Chem. Cent. J., 2018, 12(1), 138. doi: 10.1186/s13065-018-0515-1 PMID: 30569203Locarnini, S.; Littlejohn, M.; Aziz, M.N.; Yuen, L. Possible origins and evolution of the hepatitis B virus (HBV). Semin. Cancer Biol., 2013, 23(6), 561-575. doi: 10.1016/j.semcancer.2013.08.006 PMID: 24013024Lavanchy, D. Worldwide epidemiology of HBV infection, disease burden, and vaccine prevention. J. Clin. Virol., 2005, 34(Suppl. 1), S1-S3. doi: 10.1016/S1386-6532(05)00384-7 PMID: 16461208Datta, S. An overview of molecular epidemiology of hepatitis B virus (HBV) in India. Virol. J., 2008, 5(1), 156. doi: 10.1186/1743-422X-5-156 PMID: 19099581Gerasi, M.; Frakolaki, E.; Papadakis, G.; Chalari, A.; Lougiakis, N.; Marakos, P.; Pouli, N.; Vassilaki, N. Design, synthesis and anti-HBV activity evaluation of new substituted imidazo4,5-bpyridines. Bioorg. Chem., 2020, 98, 103580. doi: 10.1016/j.bioorg.2020.103580 PMID: 32005482Boček, I.; Starčević, K.; Novak Jovanović, I.; Vianello, R.; Hranjec, M. Novel imidazo4,5-bpyridine derived acrylonitriles: A combined experimental and computational study of their antioxidative potential. J. Mol. Liq., 2021, 342, 117527. doi: 10.1016/j.molliq.2021.117527Benzie, I.F.F.; Strain, J.J. The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": The FRAP assay. Anal. Biochem., 1996, 239(1), 70-76. doi: 10.1006/abio.1996.0292 PMID: 8660627