Generic placeholder image

Current Organic Chemistry


ISSN (Print): 1385-2728
ISSN (Online): 1875-5348

Review Article

A Review of Cationic Arylfurans and Their Isosteres: Synthesis and Biological Importance

Author(s): Mohamed A. Ismail*, Wael M. El-Sayed, Saad Shaaban, Ghada A. Abdelwahab and Wafaa S. Hamama*

Volume 23 , Issue 24 , 2019

Page: [2751 - 2782] Pages: 32

DOI: 10.2174/1385272823666191029114830

Price: $65


The present study provides an overview of the chemistry and biological importance of the cationic chalcophene derivatives (furans, thiophenes and selenophenes). The summarized literature survey includes synthetic methods, reactivity and biological activities of aryl/hetarylchalcophenes that have been reported mainly from 2001 to 2019 focusing on monochalcophenes. A discussion demonstrating the proposed mechanisms of some interesting synthetic routes and linking structure features to biological activities is presented. These classes of compounds including cationic chalcophenes possess antiproliferative, antimicrobial and antiprotozoal activities. This review highlights recent advances for arylchalcophene derivatives and may contribute to the design and structure optimization of new chalcophene derivatives in the future.

Keywords: Arylchalcophenes, carboxamidines, synthesis, reaction mechanisms, labelled-furans, metabolism, biological activities.

Graphical Abstract
Emsley, J. Nature's Building Blocks: An A-Z Guide to the Elements (New ed.). New York, NY: Oxford University Press, , 2011.
Jackson, M. Periodic Table Advanced., 2002.
Beyers, H.; Malan, S.; Van der Watt, J.; De Villiers, J.M. Structure-solubility relationship and thermal decomposition of furosemide. Drug Dev. Ind. Pharm., 2000, 26, 1077-1083.
Grant, S.M.; Langtry, H.D.; Brogden, R.N. Ranitidine an updated review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in peptic ulcer disease and other allied diseases. Drugs, 1989, 37, 801-870.
Bymaster, F.; Beedle, E.; Findlay, J.; Gallagher, P.; Krushinski, J.; Mitchell, S. Robertson, D.; Thompson, D.; Wallace, L.; Wong, D. Duloxetine (Cymbalta), a dual inhibitor of serotonin and norepinephrine reuptake. Bioorg. Med. Chem. Lett., 2003, 13, 4477-4480.
Krause, T.; Gerbershagen, M.; Fiege, M.; Weisshorn, R.; Wappler, F. Dantrolene- a review of its pharmacology, therapeutic use and new developments. Anaesthesia, 2004, 59, 364-373.
Mishra, R.; Jha, K.; Kumar, S.; Tomer, I. Synthesis, properties and biological activity of thiophene: a review. Pharma Chem., 2011, 3, 38-54.
Ismail, M.A.; Youssef, M.M.; Arafa, R.K.; Al-Shihry, S.S.; El-Sayed, W.M. Synthesis and anti-proliferative activity of monocationic arylthiophene derivatives. Eur. J. Med. Chem., 2017, 126, 789-798.
Ismail, M.A.; Brun, R.; Easterbrook, J.D.; Tanious, F.A.; Wilson, W.D.; Boykin, D.W. Synthesis and antiprotozoal activity of aza-analogues of furamidine. J. Med. Chem., 2003, 46, 4761-4769.
White, E.W.; Tanious, F.; Ismail, M.A.; Reszka, A.P.; Neidle, S.; Boykin, D.W.; Wilson, W.D. Structure-specific recognition of quadruplex DNA by organic cations: influence of shape, substituents and charge. Biophys. Chem., 2007, 126, 140-153.
Ismail, M.A.; El Bialy, S.A.; Brun, R.; Wenzler, T.; Nanjunda, R.; Wilson, W.D.; Boykin, D.W. Dicationic phenyl-2,2′-bichalcophenes and analogues as antiprotozoal agents. Bioorg. Med. Chem., 2011, 19, 978-984.
El-Sayed, W.M.; Hussin, W.A.; Ismail, M.A. Efficacy of two novel 2, 2′-bifurans to inhibit methicillin-resistant Staphylococcus aureus infection in male mice in comparison to vancomycin. Drug Des. Devel. Ther., 2012, 6, 279-287.
Hussin, W.A.; Ismail, M.A.; El-Sayed, W.M. Novel 4-substituted phenyl-2,2′-bichalcophenes and aza-analogs as antibacterial agents: a structural activity relationship. Drug Des. Devel. Ther., 2013, 7, 185-193.
Ismail, M.A.; Arafa, R.K.; Youssef, M.M.; El-Sayed, W.M. Anticancer, antioxidant activities, and DNA affinity of novel monocationic bithiophenes and analogues. Drug Des. Devel. Ther., 2014, 8, 1659-1672.
Ismail, M.A.; Boykin, D.W.; Stephens, C.E. An efficient Synthesis of 5,5′-diaryl-2,2′-bichalcophenes. Tetrahedron Lett., 2006, 47, 795-797.
Kim, J.S.; Ahn, H.K.; Ree, M. Synthesis and characterization of difunctional blue light-emitting molecules containing hole-transporting triphenylamino units. Tetrahedron Lett., 2005, 46, 277-279.
Hudson, J.B.; Harris, L.; Marles, R.J.; Arnason, J.T. The anti-HIV activities of photoactive terthiophenes. Photochem. Photobiol., 1993, 58, 246-250.
Ohnmacht, S.A.; Varavipour, E.; Nanjunda, R.; Pazitna, I.; Di Vita, G.; Gunaratnama, M.; Kumar, A.; Ismail, M.A.; Boykin, D.W.; Wilson, W.D. Neidle. S. Discovery of new G-quadruplex binding chemotypes. Chem. Commun. (Camb.), 2014, 50, 960-963.
Giordani, F.; Munde, M.; Wilson, W.D.; Ismail, M.A.; Kumar, A.; Boykin, D.W.; Barrett, M.P. Green fluorescent diamidines as diagnostic probes for trypanosomes. Antimicrob. Agents Chemother., 2014, 58, 1793-1796.
Demir, A.S.; Reis, Ö.; Emrullahoğlu, M. Manganese (III) acetate-mediated oxidative coupling of phenylhydrazines with furan and thiophene: a novel method for hetero biaryl coupling. Tetrahedron, 2002, 58, 8055-8058.
Reddy, G.J.; Latha, D.; Sailaja, S.; Pallavi, K.; Rao, K.S. Microwave assisted synthesis of 5-arylthiophene-2-carboxylates. Heterocycl. Commun., 2004, 10, 411-414.
Obushak, M.; Matiychuk, V.; Lytvyn, R. Synthesis and reactions of 5-aryl-2-thiophenecarbaldehydes. Chem. Heterocycl. Compd., 2008, 44, 936-940.
Hitchcock, S.A.; Mayhugh, D.R.; Gregory, G.S. Selectivity in palladium (0)-catalyzed cross-coupling reactions: application to a tandem stille reaction. Tetrahedron Lett., 1995, 36, 9085-9088.
Casado, A.L.; Espinet, P.; Gallego, A.M. Mechanism of the Stille reaction. 2. Couplings of aryl triflates with vinyltributyltin. Observation of intermediates. A more comprehensive scheme. J. Am. Chem. Soc., 2000, 122, 11771-11782.
Brendle, J.J.; Outlaw, A.; Kumar, A.; Boykin, D.W.; Patrick, D.A.; Tidwell, R.R.; Werbovetz, K.A. Antileishmanial activities of several classes of aromatic dications. Antimicrob. Agents Chemother., 2002, 46, 797-807.
Liebeskind, L.S.; Peña‐Cabrera, E. Stille couplings catalyzed by palladium‐on‐carbon with CuI as a cocatalyst: Synthesis of 2‐(4′‐Acetylphenyl) thiophene. Org. Synth., 2000, 77, 135-135.
Li, J-H.; Liang, Y.; Wang, D-P.; Liu, W-J.; Xie, Y-X.; Yin, D-L. Efficient Stille cross-coupling reaction catalyzed by the Pd(OAc)2/Dabco catalytic system. J. Org. Chem., 2005, 70, 2832-2834.
Mee, S.P.; Lee, V.; Baldwin, J.E. Significant enhancement of the Stille reaction with a new combination of reagents-copper (I) iodide with cesium fluoride. Chemistry, 2005, 11, 3294-3308.
Lu, G-P.; Cai, C.; Lipshutz, B.H. Stille couplings in water at room temperature. Green Chem., 2013, 15, 105-109.
Wu, W-Y.; Liu, L-J.; Chang, F-P.; Cheng, Y-L.; Tsai, F-Y. A highly efficient and reusable Palladium (II)/Cationic 2,2′-Bipyridyl-catalyzed Stille coupling in water. Molecules, 2016, 21, 1205.
Zhang, C.; Huang, J.; Trudell, M.L.; Nolan, S.P. Palladium-imidazol-2-ylidene complexes as catalysts for facile and efficient suzuki cross-coupling reactions of aryl chlorides with arylboronic acids. J. Org. Chem., 1999, 64, 3804-3805.
Bedford, R.B.; Cazin, C.S. Highly active catalysts for the Suzuki coupling of aryl chlorides. Chem. Commun. (Camb.), 2001, (17), 1540-1541.
Kim, S-W.; Kim, M.; Lee, W.Y.; Hyeon, T. Fabrication of hollow palladium spheres and their successful application to the recyclable heterogeneous catalyst for Suzuki coupling reactions. J. Am. Chem. Soc., 2002, 124, 7642-7643.
Bedford, R.B.; Cazin, C.S.; Hazelwood, S.L. Simple mixed tricyclohexylphosphane-triarylphosphite complexes as extremely high‐activity catalysts for the suzuki coupling of aryl chlorides. Angew. Chem. Int. Ed., 2002, 114, 4294-4296.
Leadbeater, N.E.; Marco, M. Rapid and amenable Suzuki coupling reaction in water using microwave and conventional heating. J. Org. Chem., 2003, 68, 888-892.
Tao, B.; Boykin, D.W. Simple amine/Pd(OAc)2-catalyzed Suzuki coupling reactions of aryl bromides under mild aerobic conditions. J. Org. Chem., 2004, 69, 4330-4335.
Li, S.; Lin, Y.; Cao, J.; Zhang, S. Guanidine/Pd (OAc)2-catalyzed room temperature Suzuki cross-coupling reaction in aqueous media under aerobic conditions. J. Org. Chem., 2007, 72, 4067-4072.
Jiang, Z-J.; Li, Z-H.; Yu, J-B.; Su, W-K. Liquid-assisted grinding accelerating: Suzuki-Miyaura reaction of aryl chlorides under high-speed ball-milling conditions. J. Org. Chem., 2016, 81, 10049-10055.
Park, J.; Kang, E.; Son, S.U.; Park, H.M.; Lee, M.K.; Kim, J.; Kim, K.W.; Noh, H.J.; Park, J.H.; Bae, C.J. Monodisperse nanoparticles of Ni and NiO: Synthesis, characterization, self‐assembled superlattices, and catalytic applications in the Suzuki coupling reaction. Adv. Mater., 2005, 17, 429-434.
Prediger, P.; Moro, A.V.; Nogueira, C.W.; Savegnago, L.; Menezes, P.H.; Rocha, J.B.; Zeni, G. Palladium-catalyzed Suzuki cross-coupling of 2-haloselenophenes: synthesis of 2-arylselenophenes, 2,5-diarylselenophenes, and 2-arylselenophenyl ketones. J. Org. Chem., 2006, 71, 3786-3792.
Martin, R.; Buchwald, S.L. Palladium-catalyzed Suzuki-Miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. Acc. Chem. Res., 2008, 41, 1461-1473.
Billingsley, K.; Buchwald, S.L. Highly efficient monophosphine-based catalyst for the palladium-catalyzed Suzuki- miyaura reaction of heteroaryl halides and heteroaryl boronic acids and esters. J. Am. Chem. Soc., 2007, 129, 3358-3366.
Cui, X.; Li, J.; Zhang, Z-P.; Fu, Y.; Liu, L.; Guo, Q-X. Pd (quinoline-8-carboxylate) 2 as a low-priced, phosphine-free catalyst for Heck and Suzuki reactions. J. Org. Chem., 2007, 72, 9342-9345.
Scheuermann, G.M.; Rumi, L.; Steurer, P.; Bannwarth, W.; Mülhaupt, R. Palladium nanoparticles on graphite oxide and its functionalized graphene derivatives as highly active catalysts for the Suzuki- Miyaura coupling reaction. J. Am. Chem. Soc., 2009, 131, 8262-8270.
Rizwan, K.; Zubair, M.; Rasool, N.; Mahmood, T.; Ayub, K.; Alitheen, N.B.; Aziz, M.N.M.; Akhtar, M.N.; Bukhary, S.M.; Ahmad, V.U. Palladium (0) catalyzed Suzuki cross-coupling reaction of 2, 5-dibromo-3-methylthiophene: selectivity, characterization, DFT studies and their biological evaluations. Chem. Cent. J., 2018, 12, 49.
Kim, M.J.; Jung, M.J.; Kim, Y.J.; Sung, H.K.; Lee, J.Y.; Ham, S.J.; Park, C.P. Sublimable bis (β-iminoenolate) palladium (II) complexes and their application as catalysts in Suzuki-Miyaura reactions. Tetrahedron Lett., 2018, 59, 2989-2993.
Miao, W.; Chan, T.H. Exploration of ionic liquids as soluble supports for organic synthesis. Demonstration with a Suzuki coupling reaction. Org. Lett., 2003, 5, 5003-5005.
Dong, C-G.; Hu, Q-S. Preferential oxidative addition in palladium (0)-catalyzed Suzuki cross-coupling reactions of dihaloarenes with arylboronic acids. J. Am. Chem. Soc., 2005, 127, 10006-10007.
Ikram, H.M.; Rasool, N.; Zubair, M.; Khan, K.M.; Chotana, G.M.; Akhtar, M.N.; Abu, N.; Alitheen, N.B.; Elgorban, A.M.; Rana, U.A. Efficient double Suzuki cross-coupling reactions of 2, 5-dibromo-3-hexylthiophene: anti-tumor, haemolytic, anti-thrombolytic and biofilm inhibition studies. Molecules, 2016, 21, 977.
Liu, L.; Dong, Y.; Pang, B.; Ma, J. [Bmim] PF6-promoted ligandless Suzuki-Miyaura coupling reaction of potassium aryltrifluoroborates in water. J. Org. Chem., 2014, 79, 7193-7198.
Molander, G.A.; Ellis, N. Organotrifluoroborates: protected boronic acids that expand the versatility of the Suzuki coupling reaction. Acc. Chem. Res., 2007, 40, 275-286.
Botella, L.; Nájera, C. A convenient oxime‐carbapalladacycle‐catalyzed suzuki cross‐coupling of aryl chlorides in water. Angew. Chem. Int. Ed., 2002, 41, 179-181.
Altenhoff, G.; Goddard, R.; Lehmann, C.W.; Glorius, F. An N‐heterocyclic carbene ligand with flexible steric bulk allows suzuki cross‐coupling of sterically hindered aryl chlorides at room temperature. Angew. Chem. Int. Ed., 2003, 42, 3690-3693.
Gstöttmayr, C.W.; Böhm, V.P.; Herdtweck, E.; Grosche, M.; Herrmann, W.A. A defined N‐heterocyclic carbene complex for the palladium‐catalyzed Suzuki cross‐coupling of aryl chlorides at ambient temperatures. Angew. Chem. Int. Ed., 2002, 41, 1363-1365.
Lei, P.; Meng, G.; Ling, Y.; An, J.; Szostak, M. Pd-PEPPSI: Pd-NHC precatalyst for Suzuki-Miyaura cross-coupling reactions of amides. J. Org. Chem., 2017, 82, 6638-6646.
Kondolff, I.; Doucet, H.; Santelli, M. Synthesis of biheteroaryl derivatives by tetraphosphine/palladium-catalysed Suzuki coupling of heteroaryl bromides with heteroarylboronic acids. J. Mol. Catal. Chem., 2007, 269, 110-118.
Raheem, M-A.; Nagireddy, J.R.; Durham, R.; Tam, W. Efficient procedure for the preparation of 2-bromofuran and its application in the synthesis of 2-arylfurans. Synth. Commun., 2010, 40, 2138-2146.
Lee, D-H.; Taher, A.; Hossain, S.; Jin, M-J. An efficient and general method for the Heck and Buchwald-Hartwig coupling reactions of aryl chlorides. Org. Lett., 2011, 13, 5540-5543.
Xu, H-J.; Zhao, Y-Q.; Zhou, X-F. Palladium-catalyzed Heck reaction of aryl chlorides under mild conditions promoted by organic ionic bases. J. Org. Chem., 2011, 76, 8036-8041.
Schmidt, B.; Geissler, D. Ru‐and Pd‐catalysed synthesis of 2‐arylfurans by one‐flask heck arylation/oxidation. Eur. J. Org. Chem., 2011, 2011, 4814-4822.
Lu, N.; Chen, J.Y.; Fan, C.W.; Lin, Y.C.; Wen, Y.S.; Liu, L.K. (2, 2′‐Bipyridine) palladiumdichloride derivatives as recyclable catalysts in heck reactions. J. Chin. Chem. Soc. (Taipei), 2006, 53, 1517-1521.
Yu, L.; Huang, Y.; Wei, Z.; Ding, Y.; Su, C.; Xu, Q. Heck reactions catalyzed by ultrasmall and uniform Pd nanoparticles supported on polyaniline. J. Org. Chem., 2015, 80, 8677-8683.
Bhanage, B.M.; Fujita, S-i.; Arai, M. Heck reactions with various types of palladium complex catalysts: application of multiphase catalysis and supercritical carbon dioxide. J. Organomet. Chem., 2003, 687, 211-218.
De Vries, A.H.; Mulders, J.M.; Mommers, J.H.; Henderickx, H.J.; De Vries, J.G. Homeopathic ligand-free palladium as a catalyst in the Heck reaction. A comparison with a palladacycle. Org. Lett., 2003, 5, 3285-3288.
Karimi, B.; Enders, D. New N-heterocyclic carbene palladium complex/ionic liquid matrix immobilized on silica: application as recoverable catalyst for the Heck reaction. Org. Lett., 2006, 8, 1237-1240.
Selvakumar, K.; Zapf, A.; Beller, M. New palladium carbene catalysts for the Heck reaction of aryl chlorides in ionic liquids. Org. Lett., 2002, 4, 3031-3033.
Li, H.J.; Wang, L. Triethanolamine as an efficient and reusable base, ligand and reaction medium for phosphane‐free palladium‐catalyzed Heck reactions. Eur. J. Org. Chem., 2006, 2006, 5099-5102.
Wang, A-E.; Xie, J-H.; Wang, L-X.; Zhou, Q-L. Triaryl phosphine-functionalized N-heterocyclic carbene ligands for Heck reaction. Tetrahedron, 2005, 61, 259-266.
Lipshutz, B.H.; Taft, B.R. Heck couplings at room temperature in nanometer aqueous micelles. Org. Lett., 2008, 10, 1329-1332.
Bensaid, S.; Roger, J.; Beydoun, K.; Roy, D.; Doucet, H. Direct 2-arylation of thiophene using low loading of a phosphine-free palladium catalyst. Synth. Commun., 2011, 41, 3524-3531.
Nadres, E.T.; Lazareva, A.; Daugulis, O. Palladium-catalyzed indole, pyrrole, and furan arylation by aryl chlorides. J. Org. Chem., 2011, 76, 471-483.
Rao, H.S.P.; Jothilingam, S. Facile microwave-mediated transformations of 2-butene-1, 4-diones and 2-butyne-1,4-diones to furan derivatives. J. Org. Chem., 2003, 68, 5392-5394.
Zhang, M.; Jiang, H.F.; Neumann, H.; Beller, M.; Dixneuf, P.H. Sequential synthesis of furans from alkynes: successive Ruthenium (II)‐and Copper (II)‐catalyzed processes. Angew. Chem. Int. Ed., 2009, 48, 1681-1684.
Jiang, H.; Zeng, W.; Li, Y.; Wu, W.; Huang, L.; Fu, W. Copper (I)-catalyzed synthesis of 2, 5-disubstituted furans and thiophenes from haloalkynes or 1,3-diynes. J. Org. Chem., 2012, 77, 5179-5183.
Zheng, Q.; Hua, R.; Jiang, J.; Zhang, L. A general approach to arylated furans, pyrroles, and thiophenes. Tetrahedron, 2014, 70, 8252-8256.
Yin, G.; Wang, Z.; Chen, A.; Gao, M.; Wu, A.; Pan, Y. A new facile approach to the synthesis of 3-methylthio-substituted furans, pyrroles, thiophenes, and related derivatives. J. Org. Chem., 2008, 73, 3377-3383.
Barba, F.; Velasco, M.D.; Guirado, A. Synthesis of 2,5-diarylfurans from phenacyl bromides. Synthesis, 1984, 1984, 593-595.
Kumar, A.; Stephens, C.E.; Boykin, D.W. Palladium catalyzed cross-coupling reactions for the synthesis of 2, 5-disubstitutedfurans. Heterocycl. Commun., 1999, 5, 301-304.
Stephens, C.E.; Tanious, F.; Kim, S.; Wilson, W.D.; Schell, W.A.; Perfect, J.R.; Franzblau, S.G.; Boykin, D.W. Diguanidino and “reversed” diamidino 2,5-diarylfurans as antimicrobial agents. J. Med. Chem., 2001, 44, 1741-1748.
Bajic, M.; Kumar, A.; Boykin, D.W. Synthesis of 2,5-bis-(4-cyanophenyl)-furan. Heterocycl. Commun., 1996, 2, 135-140.
Suthiwangcharoen, N.; Stephens, C.E. A new synthesis of 2, 5-bis (4-cyanophenyl) furan. ARKIVOC, 2006, 16, 122-127.
Dheur, J.; Sauthier, M.; Castanet, Y.; Mortreux, A. New synthesis of furans: the Rhodium‐catalysed carbonylative addition of arylboronic acids to propargylic alcohols/cyclisation sequence. Adv. Synth. Catal., 2010, 352, 557-561.
Trofimov, B.A.; Schmidt, E.Y.; Zorina, N.V.; Ivanova, E.V.; Ushakov, I.A. Transition-metal-free superbase-promoted stereoselective α-vinylation of ketones with arylacetylenes: a general strategy for synthesis of β, γ-unsaturated ketones. J. Org. Chem., 2012, 77, 6880-6886.
Undeela, S.; Ramchandra, J.P.; Menon, R.S. A sequential synthesis of substituted furans from aryl alkynes and ketones involving a cerium (IV) ammonium nitrate (CAN)-mediated oxidative cyclization. Tetrahedron Lett., 2014, 55, 5667-5670.
Hartmann, A.P.; de Carvalho, M.R.; Bernardes, L.S.C.; de Moraes, M.H.; de Melo, E.B.; Lopes, C.D.; Steindel, M.; da Silva, J.S.; Carvalho, I. Synthesis and 2D-QSAR studies of neolignan-based diaryl-tetrahydrofuran and-furan analogues with remarkable activity against Trypanosoma cruzi and assessment of the trypanothione reductase activity. Eur. J. Med. Chem., 2017, 140, 187-199.
Tralić-Kulenović, V.; Fiser-Jakić, L.; Lazarević, Z. Synthesis and absorption spectral properties of substituted phenylfurylbenzothiazoles and their vinylogues. Monatsh. Chem., 1994, 125, 209-215.
Boykin, D.W.; Tidwell, R.R.; Ismail, M.A.; Brun, R. Dicationic 2,5- Diarylfuran Aza-Analogs as Anti-Protozoan Agents. U.S. Patent No. 7,256,203 B2, 2007.
Ismail, M.A.; Boykin, D.W. Synthesis of deuterium-labelled 6-[5-(4-amidinophenyl) furan-2-yl] nicotinamidine and N-alkoxy-6-5-[4-(N-alkoxyamidino)phenyl]furan-2-yl-nicotinamidines. J. Labelled Comp. Radiopharm., 2004, 47, 233-242.
Ju, W.; Yang, S.; Ansede, J.H.; John, H.; Stephens, C.E.; Bridges, A.S.; Voyksner, R.D.; Ismail, M.A.; Boykin, D.W.; Tidwell, R.R.; Hall, J.E.; Wang, M.Z. CYP1A1 and CYP1B1-mediated biotransformation of the antitrypanosomal methamidoxime prodrug DB844 forms novel metabolites through intramolecular rearrangement. J. Pharm. Sci., 2014, 103, 337-349.
Ismail, M.A.; Brun, R.; Wenzler, T.; Tanious, F.A.; Wilson, W.D.; Boykin, D.W. Novel dicationic imidazo [1,2-a] pyridines and 5, 6, 7, 8-tetrahydro-imidazo[1,2-a] pyridines as antiprotozoal agents. J. Med. Chem., 2004, 47, 3658-3664.
Ismail, M.A.; Arafa, R.K.; Wenzler, T.; Brun, R.; Tanious, F.A.; Wilson, D.W.; Boykin, D.W. Synthesis and antiprotozoal activity of novel bis-benzamidino imidazo[1,2-a]pyridines and 5,6,7,8-tetrahydro imidazo[1,2-a]pyridines. Bioorg. Med. Chem., 2008, 16, 683-691.
Ismail, M.A.; Arafa, R.K.; Brun, R.; Wenzler, T.; Miao, Y.; Wilson, W.D.; Generaux, C.; Bridges, A.; Hall, J.E.; Boykin, D.W. Synthesis, DNA affinity, and antiprotozoal activity of linear dications: terphenyl diamidines and analogues. J. Med. Chem., 2006, 49, 5324-5332.
Generaux, C.N.; Ainslie, G.R.; Bridges, A.S.; Ismail, M.A.; Boykin, D.W.; Tidwell, R.R.; Thakker, D.R.; Paine, M.F. Compartmental and enzyme kinetic modeling to elucidate the biotransformation pathway of a centrally acting antitrypanosomal prodrug. Drug Metab. Dispos., 2013, 41, 518-528.
Thuita, J.K.; Wolf, K.K.; Murilla, G.A.; Liu, Q.; Hall, J.; Mutuku, N.; Chen, Y.; Bridges, A.S.; Mdachi, R.E.; Ismail, M.A.; Ching, S.; Boykin, D.W.; Hall, J.E.; Tidwell, R.R.; Paine, M.F.; Brun, R.; Wang, M.Z. Safety, Pharmacokinetic, and efficacy studies of oral DB868 in a first stage vervet monkey model of human African trypanosomiasis. PLoS Negl. Trop. Dis., 2013, 7(6)e2230
Ansede, J.H.; Voyksner, R.D.; Ismail, M.A.; Boykin, D.W.; Tidwell, R.R.; Hall, J.E. In vitro metabolism of an orally active O-Methyl amidoxime prodrug for the treatment of CNS trypanosomiasis. Xenobiotica, 2005, 35, 211-226.
Stephens, C.E.; Patrick, D.A.; Chen, H.; Tidwell, R.R.; Boykin, D.W. Synthesis of deuterium‐labelled 2, 5‐Bis (4‐amidinophenyl) furan, 2,5-bis [4- (methoxyamidino) phenyl] furan, and 2, 7‐diamidinocarbazole. J. Labelled Comp. Radiopharm., 2001, 44, 197-208.
Ismail, M.A.; Boykin, D.W. Synthesis of deuterium and 15N-labelled 2,5-bis [5-amidino-2-pyridyl]furan and 2,5-bis-[5- (methoxyamidino)-2-pyridyl]furan. J. Labelled Comp. Radiopharm., 2006, 49, 985-996.
Depauw, S.; Lambert, M.; Jambon, S.; Paul, A.; Peixoto, P.; Nhili, R.; Marongiu, L.; Figeac, M.; Dassi, C.; Paul-Constant, C.; Billoré, B.; Kumar, A.; Farahat, A.A.; Ismail, M.A.; Mineva, E.; Sweat, D.P.; Stephens, C.E.; Boykin, D.W.; Wilson, W.D.; David-Cordonnier, M.H. Heterocyclic diamidine DNA ligands as HOXA9 transcription factor inhibitors: design, molecular evaluation and cellular consequences in HOXA9-dependant leukemia cell model. J. Med. Chem., 2019, 62, 1306-1329.
Eicher, T.; Hauptmann, S.; Speicher, A. The Chemistry of Heterocycles: Structures, Reactions, Synthesis, and Applications , 3rd ed.; Wiley-VCH Verlag & Co. KGaA, Weinheim: Germany; , 2013.
Joule, J.A.; Mills, K. Heterocyclic Chemistry, 4th ed; , 2000.
Abbat, S.; Dhaked, D.; Arfeen, M.; Bharatam, P.V. Mechanism of the Paal-Knorr reaction: the importance of water mediated hemialcohol pathway. RSC Advances, 2015, 5, 88353-88366.
Shridhar, D.; Jogibhukta, M.; Rao, P.S.; Handa, V.K. An improved method for the preparation of 2,5-disubstituted thiophenes. Synthesis, 1982, 1982, 1061-1062.
Kaleta, Z.; Makowski, B.T. Soo’s, T.; Dembinski, R. Thionation using Fluorous Lawesson’s reagent. Org. Lett., 2006, 8, 1625-1628.
Amaral, M.F.; Callejon, D.R.; Riul, T.B.; Baruffi, M.D.; Toledo, F.T.; Lopes, N.P.; Clososki, G.C. Application of the Negishi reaction in the synthesis of thiophene-based lignans analogues with leishmanicidal effects. J. Braz. Chem. Soc., 2014, 25, 1907-1913.
Li, Y.; Wang, J.; Huang, M.; Wang, Z.; Wu, Y.; Wu, Y. Direct C.-H arylation of thiophenes at low catalyst loading of a phosphine-free bis(alkoxo) palladium complex. J. Org. Chem., 2014, 79, 2890-2897.
Al-Taweel, S.A. Synthesis and characterization of 2,5-Bis (2-pyridyl) thiophene. Phosphorus Sulfur Silicon Relat. Elem., 2002, 177, 1041-1045.
Urselmann, D.; Antovic, D.; Müller, T.J. Pseudo five-component synthesis of 2,5-di (hetero)arylthiophenes via a one-pot Sonogashira-Glaser cyclization sequence. Beilstein J. Org. Chem., 2011, 7, 1499-1503.
Song, J.; Wei, F.; Sun, W.; Cao, X.; Liu, C.; Xie, L.; Huang, W. Highly efficient C–C cross-coupling for installing thiophene rings into π-conjugated systems. Org. Chem. Front., 2014, 1, 817-820.
Belkessam, F.; Mohand, A.; Soulé, J.F.; Elias, A.; Doucet, H. Palladium-catalyzed 2, 5-diheteroarylation of 2,5-dibromothiophene derivatives. Beilstein J. Org. Chem., 2014, 10, 2912-2919.
Hassanpour, A.; Carufel, C.A.; Bourgault, S.; Forgione, P. Synthesis of 2,5-diaryl-substituted thiophenes as helical mimetics: towards the modulation of Islet Amyloid Polypeptide (IAPP) amyloid fibril formation and cytotoxicity. Chem. A Eur. J.,, 2014, 20, 2522-2528.
Wilson, W.D.; Nguyen, B.; Tanious, F.A.; Mathis, A.; Hall, J.E.; Stephens, C.E.; Boykin, D.W. Dications that target the DNA minor groove: compound design and preparation, DNA Interactions, cellular distribution and biological activity. Curr. Med. Chem. Anticancer Agents, 2005, 5, 389-408.
Opsenica, I.; Filipovic, V.; Nuss, J.E.; Gomba, L.M.; Opsenica, D.; Burnett, J.C.; Gussio, R.; Solaja, B.A.; Bavari, S. The synthesis of 2,5-bis(4-amidinophenyl) thiophene derivatives providing submicromolar-range inhibition of the botulinum neurotoxin serotype A metalloprotease. Eur. J. Med. Chem., 2012, 53, 374-379.
Prim, D.; Joseph, D.; Kirsch, G. Synthesis of new 2,5-diarylselenophenes. Phosphorus Sulfur Silicon Relat. Elem., 1994, 91, 137-143.
Hua, G.; Henry, J.B.; Li, Y.; Mount, A.R.; Slawin, A.M.; Woollins, J.D. Synthesis of novel 2,5-diarylselenophenes from selenation of 1,4-diarylbutane-1,4-diones or methanol/arylacetylenes. Org. Biomol. Chem., 2010, 8, 1655-1660.
Tidwell, R.R.; Boykin, D.W.; Stephens, C.E.; Ismail, M.A.; Kumar, A.; Wilson, W.D.; Brun, R.; Werbovetz, K. 2,5-diarylselenophene compounds, aza 2,5-diarylthiophene compounds, and their prodrugs as antiprotozoal agents. U.S. Patent No. 2010/0331368 A1, December 30, 2010.
Skhiri, A.; Salem, R.B.; Soulé, J.F.; Doucet, H. Reactivity of bromoselenophenes in palladium-catalyzed direct arylations. Beilstein J. Org. Chem., 2017, 13, 2862-2868.
Thomas, J.; Jecic, A.; Vanstreels, E.; van Berckelaer, L.; Romagnoli, R.; Dehaen, W.; Liekens, S.; Balzarini, J. Pronounced anti-proliferative activity and tumor cell selectivity of 5-alkyl-2-amino-3-methylcarboxylate thiophenes. Eur. J. Med. Chem., 2017, 132, 219-235.
Nanjunda, R.; Musetti, C.; Kumar, A.; Ismail, M.A.; Farahat, A.A.; Wang, S.; Sissi, C.; Palumbo, M.; Boykin, D.W.; Wilson, W.D. Heterocyclic dications as a new class of telomeric G-quadruplex targeting agents. Curr. Pharm. Des., 2012, 18, 1934-1947.
Neidle, S.; Parkinson, G.N. Quadruplex DNA crystal structures and drug design. Biochimie, 2008, 90, 1184-1196.
Neidle, S.; Thurston, D.E. Chemical approaches to the discovery and development of cancer therapies. Nat. Rev. Cancer, 2005, 5, 285-296.
Hurley, L.H. DNA and its associated processes as targets for cancer therapy. Nat. Rev. Cancer, 2002, 2, 188-200.
Rezler, E.M.; Bearss, D.J.; Hurley, L.H. Telomeres and telomerases as drug targets. Curr. Opin. Pharmacol., 2002, 2, 415-423.
Bailly, C.; Dassonneville, L.; Carrascol, C.; Lucasl, D.; Kumar, A.; Boykin, D.W.; Wilson, W.D. Relationships between topoisomerase II inhibition, sequence-specificity and DNA binding mode of dicationic diphenylfuran derivatives. Anticancer Drug Des., 1999, 14, 47-60.
Wilson, W.D.; Tanious, F.; Ding, D.; Kumar, A.; Boykin, D.W.; Colson, P.; Houssier, C.; Bailly, C. Nucleic acid interactions of unfused aromatic cations: evaluation of proposed minor-groove, major-groove and intercalation binding modes. J. Am. Chem. Soc., 1998, 120, 10310-10321.
Liu, Y.; Kumar, A.; Depauw, S.; Nhili, R.; David-Cordonnier, M.; Lee, M.P.; Ismail, M.A.; Farahat, A.A.; Say, M.; Chackal-Catoen, S.; Batista-Parra, A.; Neidle, S.; Boykin, D.W.; Wilson, W.D. Water-mediated binding of agents that target the DNA minor groove. J. Am. Chem. Soc., 2011, 133, 10171-10183.
Fitzgerald, D.J.; Anderson, J.N. Selective nucleosome disruption by drugs that bind in the minor groove of DNA. J. Biol. Chem., 1999, 274, 27128-27138.
Dykstra, C.C.; McClernon, D.R.; Elwell, L.P.; Tidwell, R.R. Selective inhibition of topoisomerases from Pneumocystis carinii compared with that of topoisomerases from mammalian cells. Antimicrob. Agents Chemother., 1994, 38, 1890-1898.
Nguyen, B.; Tardy, C.; Bailly, C.; Colson, P.; Houssier, C.; Kumar, A.; Boykin, D.W.; Wilson, W.D. Influence of compound structure on affinity, sequence selectivity, and mode of binding to DNA for unfused aromatic dications related to furamidine. Biopolymers, 2002, 63, 281-297.
Youssef, M.M.; Arafa, R.K.; Ismail, M.A. Synthesis, antimicrobial, and anti-proliferative activities of substituted phenylfuranylnicotinamidines. Drug Des. Devel. Ther., 2016, 10, 1133-1146.
Wenzler, T.; Boykin, D.W.; Ismail, M.A.; Hall, J.E.; Tidwell, R.R.; Brun, R. New treatment option for second-stage African sleeping sickness: in vitro and in vivo efficacy of aza analogs of DB289. Antimicrob. Agents Chemother., 2009, 53, 4185-4192.
Thuita, J.K.; Wolf, K.K.; Murilla, G.A.; Bridges, A.S.; Boykin, D.W.; Mutuku, J.N.; Liu, Q.; Jones, S.K.; Gem, C.O.; Ching, S.; Tidwell, R.R.; Wang, M.Z.; Paine, M.F.; Brun, R. Chemotherapy of second stage human African trypanosomiasis: comparison between the parenteral diamidine DB829 and its oral prodrug DB868 in vervet monkeys.PLoS Negl. Trop. Dis., 2015, 9e0003409 ,
Wenzler, T.; Yang, S.; Braissant, O.; Boykin, D.W.; Brun, R.; Wang, M.Z. Pharmacokinetics, Trypanosoma brucei gambiense efficacy, and time of drug action of DB829, a preclinical candidate for treatment of second-stage human African trypanosomiasis. Antimicrob. Agents Chemother., 2013, 57, 5330-5343.
Patrick, D.A.; Ismail, M.A.; Arafa, R.K.; Wenzler, T.; Zhu, X.; Pandharkar, T.S.; Jones, S.K.; Werbovetz, K.A.; Brun, R.; Boykin, D.W.; Tidwell, R.R. Synthesis and antiprotozoal activity of dicationic m-terphenyl and 1,3-dipyridylbenzene derivatives. J. Med. Chem., 2013, 56, 5473-5494.
Wenzler, T.; Yang, S.; Patrick, D.A.; Braissant, O.; Ismail, M.A.; Tidwell, R.R.; Boykin, D.W.; Wang, M.Z. Brun. R. In vitro and in vivo evaluation of 28DAP010, a novel diamidine for treatment of second-stage African sleeping sickness. Antimicrob. Agents Chemother., 2014, 58, 4452-4463.
Ward, C.P.; Burgess, K.E.V.; Burchmore, R.J.S.; Barrett, M.P.; De Koning, H.P. A fluorescence-based assay for the uptake of CPD0801 (DB829) by African trypanosomes. Mol. Biochem. Parasitol., 2010, 174, 145-149.
Ward, C.P.; Ee Wong, P.; Burchmore, R.J.; de Koning, H.P.; Barrett, M.P. Trypanocidal furamidine analogues: influence of pyridine nitrogens on trypanocidal activity, transport kinetics, and resistance patterns. Antimicrob. Agents Chemother., 2011, 55, 2352-2361.
Hu, L.; Arafa, R.K.; Ismail, M.A.; Patel, A.; Munde, M.; Wilson, D.W.; Wenzler, T.; Brun, R.; Boykin, D.W. Synthesis and activity of azaterphenyl diamidines against Trypanosoma brucei, Rhodesiense and Plasmodium falciparum. Bioorg. Med. Chem., 2009, 17, 6651-6658.
Hu, L.; Arafa, R.K.; Ismail, M.A.; Wenzler, T.; Brun, R.; Munde, M.; Wilson, D.W.; Nzimiro, S.; Samyesudhas, S.; Werbovetz, K.A.; Boykin, D.W. Azaterphenyl diamidines as antileishmanial agents. Bioorg. Med. Chem. Lett., 2008, 18, 247-251.
Guo, P.; Farahat, A.A.; Paul, A.; Harika, N.K.; Boykin, D.W.; Wilson, W.D. compound shape effects in minor groove binding affinity and specificity for mixed sequence DNA. J. Am. Chem. Soc., 2018, 140, 14761-14769.
Guo, P.; Paul, A.; Kumar, A.; Harika, N.K.; Wang, S.; Farahat, A.A.; Boykin, D.W.; Wilson, W.D. A modular design for minor groove binding and recognition of mixed base pair sequences of DNA. Chem. Commun. (Camb.), 2017, 53, 10406-10409.
Guo, P.; Paul, A.; Kumar, A.; Farahat, A.A.; Kumar, D.; Wang, S.; Boykin, D.W.; Wilson, W.D. The thiophene “Sigma‐Hole” as a concept for preorganized, specific recognition of G⋅ C base pairs in the DNA minor groove. Chem. -A Eur. J., 2016, 22, 15404-15412.
Ismail, M.A.; Negm, A.; Arafa, R.K.; Abdel-Latif, E.; El-Sayed, W.M. Anticancer activity, dual prooxidant/antioxidant effect and apoptosis induction profile of new bichalcophene-5-carboxamidines. Eur. J. Med. Chem., 2019, 169, 76-88.
Nhili, R.; Peixoto, P.; Depauw, S.; Flajollet, S. Dezitter, X.; M. Munde, M.; Ismail, M.A.; Kumar, A.; Farahat, A.A.; Stephens, C.E.; Duterque-Coquillaud, M.; Wilson, W.D.; Boykin, D.W.; David-Cordonnier, M.H. Targeting the DNA-binding activity of the human ERG transcription factor using new heterocyclic dithiophene diamidines. Nucleic Acids Res., 2013, 41, 125-138.
Simone, R.; Balendra, R.R.; Moens, T.G.; Preza, E.; Wilson, K.M.; Heslegrave, A.; Woodling, N.S.; Niccoli, T.; Gilbert-Jaramillo, J.; Abdelkarim, S.; Clayton, E.L.; Clarke, M.; Konrad, M-T.; Nicoll, A.J.; Calvo, A.; Chio, A.; Houlden, H.; Polke, J.M.; Ismail, M.A.; Stephens, C.E.; Vo, T.; Farahat, A.A.; Wilson, W.D.; Boykin, D.W.; Zetterberg, H.; Partridge, L.; Wray, S.; Parkinson, G.; Neidle, S.; Patani, R.; Fratta, P.; Isaacs, A.M. G-quadruplex-binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and in vivo. EMBO Mol. Med., 2018, 10, 22-31.
Antony-Debré, I.; Paul, A.; Leite, J.; Mitchell, K.; Kim, H.M.; Carvajal, L.A.; Todorova, T.I.; Huang, K.; Kumar, A.; Farahat, A.A.; Bartholdy, B.; Narayanagari, S-R.; Chen, J.; Ambesi-Impiombato, A.; Ferrando, A.A.; Mantzaris, I.; Gavathiotis, E.; Verma, A.; Will, B.; Boykin, D.W.; Wilson, W.D.; Poon, G.M.K.; Steidl, U. Pharmacological inhibition of the transcription factor PU.1 in leukemia. J. Clin. Invest., 2017, 127, 4297-4313.
Munde, M.; Kumar, A.; Peixoto, P.; Depauw, S.; Ismail, M.A.; Farahat, A.A.; Paul, A.; Say, M.V.; David-Cordonnier, M-H.; Boykin, D.W.; Wilson, W.D. The unusual monomer recognition of guanine-containing mixed sequence DNA by a dithiophene heterocyclic diamidine. Biochemistry, 2014, 53, 1218-1227.
Ansede, J.H.; Anbazhagan, M.; Brun, R.; Easterbrook, J.D.; Hall, J.E.; Boykin, D.W. O-Alkoxyamidine prodrugs of furamidine: in vitro transport and microsomal metabolism as indicators of in vivo efficacy in a mouse model of Trypanosoma brucei rhodesiense infection. J. Med. Chem., 2004, 47, 4335-4338.
Gillingwater, K.; Gutierrez, C.; Bridges, A.; Wu, H.; Deborggrave, S.; Ekangu, R.; Kumar, A.; Ismail, M.; Boykin, D.; Brun, R. Efficacy study of novel diamidine compounds in a Trypanosoma evansi goat model. PLoS One, 2011, 6e20836

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy