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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

New Approaches for the Synthesis of Heterocyclic Compounds Corporating Benzo[d]imidazole as Anticancer Agents, Tyrosine, Pim-1 Kinases Inhibitions and their PAINS Evaluations

Author(s): Rafat M. Mohareb*, Yara R. Milad, Bahaa M. Mostafa and Reem A. El-Ansary

Volume 21, Issue 3, 2021

Published on: 21 July, 2020

Page: [327 - 342] Pages: 16

DOI: 10.2174/1871520620666200721111230

Price: $65

Abstract

Background: Benzo[d]imidazoles are highly biologically active, in addition, they are considered as a class of heterocyclic compounds with many pharmaceutical applications.

Objective: We are aiming in this work to synthesize target molecules that possess not only anti-tumor activities but also kinase inhibitors. The target molecules were obtained starting from the benzo[d]imidazole derivatives followed by their heterocyclization reactions to produce anticancer target molecules.

Methods: The 1-(1H-benzo[d]imidazol-2-yl)propan-2-one (3) and the ethyl 2-(1H-benzo[d]imidazol-2- yl)acetate (16) were used as the key starting material which reacted with salicylaldehyde to give the corresponding benzo[4,5]imidazo[1,2-a]quinoline derivatives. On the other hand, both of them were reacted with different reagents to give thiophene, pyran and benzo[4,5]imidazo[1,2-c]pyrimidine derivatives. The synthesized compounds were evaluated against the six cancer cell lines A549, HT-29, MKN-45, U87MG, SMMC-7721, and H460 together with inhibitions toward tyrosine kinases, c-Met kinase and prostate cancer cell line PC-3 using the standard MTT assay in vitro, with foretinib as the positive control.

Results: Most of the synthesized compounds exhibited high inhibitions toward the tested cancer cell lines. In addition, tyrosine and Pim-1 kinases inhibitions were performed for the most active compounds where the variation of substituent through the aryl ring and heterocyclic ring afforded compounds with high activities. Our analysis showed that there is a strong correlation between the structure of the compound and the substituents of target molecules.

Conclusion: Our present research proved that the synthesized heterocyclic compounds with varieties of substituents have a strong impact on the activity of compounds. The evaluations through different cell lines and tyrosine kinases indicated that the compounds were the excellent candidates as anticancer agents. This could encourage doing further research within this field for the building of compounds with high inhibitions.

Keywords: Benzo[d]midazole, thiophene, quinoline, cytotoxicity, tyrosine kinases, PAINS alert.

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[1]
Kazimierczuk, Z.; Upcroft, J.A.; Upcroft, P.; Górska, A.; Starościak, B.; Laudy, A. Synthesis, antiprotozoal and antibacterial activity of nitro- and halogeno-substituted benzimidazole derivatives. Acta Biochim. Pol., 2002, 49(1), 185-195.
[http://dx.doi.org/10.18388/abp.2002_3835] [PMID: 12136939]
[2]
Göker, H.; Kuş, C.; Boykin, D.W.; Yildiz, S.; Altanlar, N. Synthesis of some new 2-substituted-phenyl-1H-benzimidazole-5-carbonitriles and their potent activity against Candida species. Bioorg. Med. Chem., 2002, 10(8), 2589-2596.
[http://dx.doi.org/10.1016/S0968-0896(02)00103-7] [PMID: 12057648]
[3]
Klimesová, V.; Kocí, J.; Pour, M.; Stachel, J.; Waisser, K.; Kaustová, J. Synthesis and preliminary evaluation of benzimidazole derivatives as antimicrobial agents. Eur. J. Med. Chem., 2002, 37(5), 409-418.
[http://dx.doi.org/10.1016/S0223-5234(02)01342-9] [PMID: 12008055]
[4]
Pawar, N.S.; Dalal, D.S.; Shimpi, S.R.; Mahulikar, P.P. Studies of antimicrobial activity of N-alkyl and N-acyl 2-(4-thiazolyl)-1H-benzimidazoles. Eur. J. Pharm. Sci., 2004, 21(2-3), 115-118.
[http://dx.doi.org/10.1016/j.ejps.2003.09.001] [PMID: 14757482]
[5]
Boiani, M.; González, M. Imidazole and benzimidazole derivatives as chemotherapeutic agents. Mini Rev. Med. Chem., 2005, 5(4), 409-424.
[http://dx.doi.org/10.2174/1389557053544047] [PMID: 15853629]
[6]
Desai, K.G.; Desai, K.R. Green route for the heterocyclization of 2-mercaptobenzimidazole into β-lactum segment derivatives containing -CONH- bridge with benzimidazole: Screening in vitro antimicrobial activity with various microorganisms. Bioorg. Med. Chem., 2006, 14(24), 8271-8279.
[http://dx.doi.org/10.1016/j.bmc.2006.09.017] [PMID: 17035035]
[7]
Mohamed, B.G.; Hussein, M.A.; Abdel-Alim, A.A.; Hashem, M. Synthesis and antimicrobial activity of some new 1-alkyl-2-alkylthio-1,2,4-triazolobenzimidazole derivatives. Arch. Pharm. Res., 2006, 29(1), 26-33.
[http://dx.doi.org/10.1007/BF02977464] [PMID: 16491839]
[8]
Güven, O.O.; Erdoğan, T.; Göker, H.; Yildiz, S. Synthesis and antimicrobial activity of some novel phenyl and benzimidazole substituted benzyl ethers. Bioorg. Med. Chem. Lett., 2007, 17(8), 2233-2236.
[http://dx.doi.org/10.1016/j.bmcl.2007.01.061] [PMID: 17289382]
[9]
O’Niel, M.J.; Smith, M.; Heckelman, P.E. The Merck Index; Merck Co. Inc.: New Jersey, 2001.
[10]
Ayhan-Kilcigil, G.; Kus, C.; Ozdamar, E.D.; Can-Eke, B.; Iscan, M. Antioxidant properties of 5-[2-(phenyl)-benzimidazol-1-yl-methyl]-2-mercapto-[1,3,4]-oxadiazole in rat liver. Toxicol. Lett., 2008, 180, S94.
[http://dx.doi.org/10.1016/j.toxlet.2008.06.491]
[11]
Jafar, A.A.; Vijayakumar, K.N.; Venkatraman, B.R.; Venkatesha, G. Synthesis, characterization and biological activity of some novel benzimidazole derivatives. Orbital, 2009, 1, 306-309.
[12]
Ateş-Alagöz, Z.; Kuş, C.; Coban, T. Synthesis and antioxidant properties of novel benzimidazoles containing substituted indole or 1,1,4,4-tetramethyl-1,2,3,4-tetrahydro-naphthalene fragments. J. Enzyme Inhib. Med. Chem., 2005, 20(4), 325-331.
[http://dx.doi.org/10.1080/14756360500131706] [PMID: 16206826]
[13]
Navarrete-Vázquez, G.; Cedillo, R.; Hernández-Campos, A.; Yépez, L.; Hernädez-Luis, F.; Valdez, J.; Morales, R.; Cortés, R.; Hernández, M.; Castillo, R. Synthesis and antiparasitic activity of 2-(trifluoromethyl)-benzimidazole derivatives. Bioorg. Med. Chem. Lett., 2001, 11(2), 187-190.
[http://dx.doi.org/10.1016/S0960-894X(00)00619-3] [PMID: 11206455]
[14]
Katiyar, S.K.; Gordon, V.R.; McLaughlin, G.L.; Edlind, T.D. Antiprotozoal activities of benzimidazoles and correlations with beta-tubulin sequence. Antimicrob. Agents Chemother., 1994, 38(9), 2086-2090.
[http://dx.doi.org/10.1128/AAC.38.9.2086] [PMID: 7811023]
[15]
Thriveni, P.; Rao, K.P.V.; Krishna, M.H. Facile and efficient one-pot synthesis of benzimidazoles using boron trichloride. J. Chem. Pharm. Res., 2016, 8, 1242-1245.
[16]
Garuti, L.; Roberti, M.; Malagoli, M.; Rossi, T.; Castelli, M. Synthesis and antiproliferative activity of some benzimidazole-4,7-dione derivatives. Bioorg. Med. Chem. Lett., 2000, 10(19), 2193-2195.
[http://dx.doi.org/10.1016/S0960-894X(00)00429-7] [PMID: 11012027]
[17]
Rao, A.; Chimirri, A.; De Clercq, E.; Monforte, A.M.; Monforte, P.; Pannecouque, C.; Zappalà, M. Synthesis and anti-hIV activity of 1-(2,6-difluorophenyl)-1H,3H-thiazolo[3,4-a]benzimidazole structurally-related 1,2-substituted benzimidazoles. Farmaco, 2002, 57(10), 819-823.
[http://dx.doi.org/10.1016/S0014-827X(02)01300-9] [PMID: 12420877]
[18]
Chimirri, A.; De Sarro, A.; De Sarro, G.; Gitto, R.; Zappalà, M. Synthesis and anticonvulsant properties of 2,3,3a,4-tetrahydro-1H-pyrrolo[1,2-a]benzimidazol-1-one derivatives. Farmaco, 2001, 56(11), 821-826.
[http://dx.doi.org/10.1016/S0014-827X(01)01147-8] [PMID: 11765033]
[19]
Thakurdesai, P.A.; Wadodkar, S.G.; Chopade, C.T. Synthesis and anti-nflammatory activity of some benzimidazole-2-carboxylic acids. Pharmacologyonline, 2007, 1, 314-329.
[20]
Le, H.T.; Lemaire, I.B.; Gilbert, A.K.; Jolicoeur, F.; Yang, L.; Leduc, N.; Lemaire, S. Histogranin-like antinociceptive and anti-inflammatory derivatives of o-phenylenediamine and benzimidazole. J. Pharmacol. Exp. Ther., 2004, 309(1), 146-155.
[http://dx.doi.org/10.1124/jpet.103.060772] [PMID: 14718586]
[21]
Lackner, T.E.; Clissold, S.P. Bifonazole. A review of its antimicrobial activity and therapeutic use in superficial mycoses. Drugs, 1989, 38(2), 204-225.
[http://dx.doi.org/10.2165/00003495-198938020-00004] [PMID: 2670516]
[22]
Ersan, S.; Nacak, S.; Noyanalpan, N.; Yeşilada, E. Studies on analgesic and anti-inflammatory activities of 1-dialkylaminomethyl-2-(p-substituted phenyl)-5-substituted benzimidazole derivatives. Arzneimittelforschung, 1997, 47(7), 834-836.
[PMID: 9272240]
[23]
Serafin, B.; Borkowska, G.; Główczyk, J.; Kowalska, I.; Rump, S. Potential antihypertensive benzimidazole derivatives. Pol. J. Pharmacol. Pharm., 1989, 41(1), 89-96.
[PMID: 2587441]
[24]
Kubo, K.; Inada, Y.; Kohara, Y.; Sugiura, Y.; Ojima, M.; Itoh, K.; Furukawa, Y.; Nishikawa, K.; Naka, T. Nonpeptide angiotensin II receptor antagonists. Synthesis and biological activity of benzimidazoles. J. Med. Chem., 1993, 36(12), 1772-1784.
[http://dx.doi.org/10.1021/jm00064a011] [PMID: 8510105]
[25]
Abdel-monem Abdel-hafez. A. Benzimidazole condensed ring systems: new synthesis and antineoplastic activity of substituted 3,4-dihydro- and 1,2,3,4-tetrahydro-benzo[4,5]imidazo[1,2-a]pyrimidine derivatives. Arch. Pharm. Res., 2007, 30(6), 678-684.
[http://dx.doi.org/10.1007/BF02977627] [PMID: 17679543]
[26]
Ram, S.; Wise, D.S.; Wotring, L.L.; McCall, J.W.; Townsend, L.B. Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates and related derivatives: a new class of potential antineoplastic and antifilarial agents. J. Med. Chem., 1992, 35(3), 539-547.
[http://dx.doi.org/10.1021/jm00081a016] [PMID: 1738146]
[27]
Mavrova, A.T.; Denkova, P.; Tsenov, Y.A.; Anichina, K.K.; Vutchev, D.I. Synthesis and antitrichinellosis activity of some bis(benzimidazol-2-yl)amines. Bioorg. Med. Chem., 2007, 15(18), 6291-6297.
[http://dx.doi.org/10.1016/j.bmc.2007.06.017] [PMID: 17600722]
[28]
Sun, L.; Li, D.; Dong, X.; Yu, H.; Dong, J.T.; Zhang, C.; Lu, X.; Zhou, J. Small-molecule inhibition of Aurora kinases triggers spindle checkpoint-independent apoptosis in cancer cells. Biochem. Pharmacol., 2008, 75(5), 1027-1034.
[http://dx.doi.org/10.1016/j.bcp.2007.11.007] [PMID: 18163976]
[29]
Njar, V.C.; Brodie, A.M. Discovery and development of galeterone. Discovery and development of galeterone (TOK-001 or VN/124-1) for the treatment of all stages of prostate cancer. J. Med. Chem., 2015, 58(5), 2077-2087.
[http://dx.doi.org/10.1021/jm501239f] [PMID: 25591066]
[30]
Penning, T.D.; Zhu, G.D.; Gandhi, V.B.; Gong, J.; Liu, X.; Shi, Y.; Klinghofer, V.; Johnson, E.F.; Donawho, C.K.; Frost, D.J.; Bontcheva-Diaz, V.; Bouska, J.J.; Osterling, D.J.; Olson, A.M.; Marsh, K.C.; Luo, Y.; Giranda, V.L. Discovery of the Poly(ADP-ribose) polymerase (PARP) inhibitor 2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide (ABT-888) for the treatment of cancer. J. Med. Chem., 2009, 52(2), 514-523.
[http://dx.doi.org/10.1021/jm801171j] [PMID: 19143569]
[31]
Mahesh, D.; Sadhu, P.; Punniyamurthy, T. Copper(I)-catalyzed regioselective amination of N-aryl imines using TMSN3 and TBHP: a route to substituted benzimidazoles. J. Org. Chem., 2015, 80(3), 1644-1650.
[http://dx.doi.org/10.1021/jo502574u] [PMID: 25588127]
[32]
Ryabukhin, S.V.; Plaskon, A.S.; Ostapchuk, E.N.; Volochnyuk, D.M.; Tolmachev, A.A. N-substituted ureas and thioureas in biginelli reaction promoted by chlorotrimethylsilane: Convenient synthesis of N1-alkyl-, N1-aryl-, and N1,N3-dialkyl-3,4-dihydropyrimidin-2(1H)- thiones. Synthesis, 2007, 3, 417-427.
[33]
Beaulieu, P.L.; Haché, B.; von Moos, E. A practical Oxone®-mediated, high-throughput, solution-phase synthesis of benzimidazoles from 1,2-phenylenediamines and aldehydes and its application to preparative scale synthesis. Synthesis, 2003, 11, 1683-1692.
[http://dx.doi.org/10.1055/s-2003-40888]
[34]
Baars, H.; Beyer, A.; Kohlhepp, S.V.; Bolm, C. Transition-metal-free synthesis of benzimidazoles mediated by KOH/DMSO. Org. Lett., 2014, 16(2), 536-539.
[http://dx.doi.org/10.1021/ol403414v] [PMID: 24364511]
[35]
Kim, Y.; Kumar, M.R.; Park, N.; Heo, Y.; Lee, S. Copper-catalyzed, one-pot, three-component synthesis of benzimidazoles by condensation and C-N bond formation. J. Org. Chem., 2011, 76(23), 9577-9583.
[http://dx.doi.org/10.1021/jo2019416] [PMID: 22034860]
[36]
Patel, V.K.; Singh, A.; Jain, D.K.; Patel, P.; Veerasamy, R.; Sharma, P.C.; Rajak, H. Combretastatin A-4 based thiophene derivatives as antitumor agent: Development of structure activity correlation model using 3D-QSAR, pharmacophore and docking studies. Future J. Pharamceut. Sci., 2017, 3, 71-78.
[http://dx.doi.org/10.1016/j.fjps.2017.03.003]
[37]
Khaligh, N.G.; Mihankhah, T.; Johan, M.R. Synthesis of new low-viscous sulfonic acid-functionalized ionic liquid and its application as a Brönsted liquid acid catalyst for the one-pot mechanosynthesis of 4H-pyrans through the ball milling process. J. Mol. Liq., 2019, 277, 794-804.
[http://dx.doi.org/10.1016/j.molliq.2019.01.024]
[38]
Kulandasamy, R.; Adhikari, A.V.; Stables, J.P. A new class of anticonvulsants possessing 6 Hz activity: 3,4-dialkyloxy thiophene bishydrazones. Eur. J. Med. Chem., 2009, 44(11), 4376-4384.
[http://dx.doi.org/10.1016/j.ejmech.2009.05.026] [PMID: 19556038]
[39]
Das, B.; Laxminarayana, K.; Krishnaiah, M.; Kumar, D.N. Stereoselective total synthesis of a potent natural antifungal compound (6S)-5,6,dihydro-6-[(2R)-2-hydroxy-6-phenyl hexyl]-2H-pyran-2-one. Bioorg. Med. Chem. Lett., 2009, 19(22), 6396-6398.
[http://dx.doi.org/10.1016/j.bmcl.2009.09.063] [PMID: 19811917]
[40]
Almansour, A.I.; Suresh Kumar, R.; Arumugam, N.; Sriram, D. A solvent free, four-component synthesis and 1,3-dipolar cycloaddition of 4(H)-pyrans with nitrile oxides: Synthesis and discovery of antimycobacterial activity of enantiomerically pure 1,2,4-oxadiazoles. Eur. J. Med. Chem., 2012, 53, 416-423.
[http://dx.doi.org/10.1016/j.ejmech.2012.04.021] [PMID: 22575534]
[41]
Liu, L.; Siegmund, A.; Xi, N.; Kaplan-Lefko, P.; Rex, K.; Chen, A.; Lin, J.; Moriguchi, J.; Berry, L.; Huang, L.; Teffera, Y.; Yang, Y.; Zhang, Y.; Bellon, S.F.; Lee, M.; Shimanovich, R.; Bak, A.; Dominguez, C.; Norman, M.H.; Harmange, J.C.; Dussault, I.; Kim, T.S. Discovery of a potent, selective, and orally bioavailable c-Met inhibitor: 1-(2-hydroxy-2-methylpropyl)-N-(5-(7-methoxyquinolin-4-yloxy)pyridin-2-yl)-5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazole-4-carboxamide (AMG 458). J. Med. Chem., 2008, 51(13), 3688-3691.
[http://dx.doi.org/10.1021/jm800401t] [PMID: 18553959]
[42]
DiSalvo, J.; Bayne, M.L.; Conn, G.; Kwok, P.W.; Trivedi, P.G.; Soderman, D.D.; Palisi, T.M.; Sullivan, K.A.; Thomas, K.A. Purification and characterization of a naturally occurring vascular endothelial growth factor.placenta growth factor heterodimer. J. Biol. Chem., 1995, 270(13), 7717-7723.
[http://dx.doi.org/10.1074/jbc.270.13.7717] [PMID: 7706320]
[43]
Senger, D.R.; Galli, S.J.; Dvorak, A.M.; Perruzzi, C.A.; Harvey, V.S.; Dvorak, H.F. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid. Science, 1983, 219(4587), 983-985.
[http://dx.doi.org/10.1126/science.6823562] [PMID: 6823562]
[44]
Ferrara, N. VEGF and the quest for tumour angiogenesis factors. Nat. Rev. Cancer, 2002, 2(10), 795-803.
[http://dx.doi.org/10.1038/nrc909] [PMID: 12360282]
[45]
Rubin, J.S.; Bottaro, D.P.; Aaronson, S.A. Hepatocyte growth factor/scatter factor and its receptor, the c-met proto-oncogene product. Biochim. Biophys. Acta, 1993, 1155(3), 357-371.
[PMID: 8268192]
[46]
Organ, S.L.; Tsao, M.S. An overview of the c-MET signaling pathway. Ther. Adv. Med. Oncol., 2011, 3(1)(Suppl.), S7-S19.
[http://dx.doi.org/10.1177/1758834011422556] [PMID: 22128289]
[47]
Humphrey, P.A.; Zhu, X.; Zarnegar, R.; Swanson, P.E.; Ratliff, T.L.; Vollmer, R.T.; Day, M.L. Hepatocyte growth factor and its receptor (c-MET) in prostatic carcinoma. Am. J. Pathol., 1995, 147(2), 386-396.
[PMID: 7639332]
[48]
Jeffers, M.; Rong, S.; Vande Woude, G.F. Hepatocyte growth factor/scatter factor-Met signaling in tumorigenicity and invasion/metastasis. J. Mol. Med. (Berl.), 1996, 74(9), 505-513.
[http://dx.doi.org/10.1007/BF00204976] [PMID: 8892055]
[49]
Verras, M.; Lee, J.; Xue, H.; Li, T.H.; Wang, Y.; Sun, Z. The androgen receptor negatively regulates the expression of c-Met: Implications for a novel mechanism of prostate cancer progression. Cancer Res., 2007, 67(3), 967-975.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3552] [PMID: 17283128]
[50]
De Bacco, F.; Luraghi, P.; Medico, E.; Reato, G.; Girolami, F.; Perera, T.; Gabriele, P.; Comoglio, P.M.; Boccaccio, C. Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer. J. Natl. Cancer Inst., 2011, 103(8), 645-661.
[http://dx.doi.org/10.1093/jnci/djr093] [PMID: 21464397]
[51]
Li, S.; Zhao, Y.; Wang, K.; Gao, Y.; Han, J.; Cui, B.; Gong, P. Discovery of novel 4-(2-fluorophenoxy)quinoline derivatives bearing 4-oxo-1,4-dihydrocinnoline-3-carboxamide moiety as c-Met kinase inhibitors. Bioorg. Med. Chem., 2013, 21(11), 2843-2855.
[http://dx.doi.org/10.1016/j.bmc.2013.04.013] [PMID: 23628470]
[52]
Zhu, W.; Wang, W.; Xu, S.; Wang, J.; Tang, Q.; Wu, C.; Zhao, Y.; Zheng, P. Synthesis, and docking studies of phenylpyrimidine-carboxamide derivatives bearing 1H-pyrrolo[2,3-b]pyridine moiety as c-Met inhibitors. Bioorg. Med. Chem., 2016, 24(8), 1749-1756.
[http://dx.doi.org/10.1016/j.bmc.2016.02.046] [PMID: 26964675]
[53]
Baell, J.B.; Holloway, G.A. New substructure filters for removal of Pan Assay Interference compounds (PAINS) from screening libraries and for their exclusion in bioassays. J. Med. Chem., 2010, 53(7), 2719-2740.
[http://dx.doi.org/10.1021/jm901137j] [PMID: 20131845]
[54]
McGovern, S.L.; Caselli, E.; Grigorieff, N.; Shoichet, B.K. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J. Med. Chem., 2002, 45(8), 1712-1722.
[http://dx.doi.org/10.1021/jm010533y] [PMID: 11931626]
[55]
McGovern, S.L.; Shoichet, B.K. Kinase inhibitors: Not just for kinases anymore. J. Med. Chem., 2003, 46(8), 1478-1483.
[http://dx.doi.org/10.1021/jm020427b] [PMID: 12672248]
[56]
Feng, B.Y.; Shelat, A.; Doman, T.N.; Guy, R.K.; Shoichet, B.K. High-throughput assays for promiscuous inhibitors. Nat. Chem. Biol., 2005, 1(3), 146-148.
[http://dx.doi.org/10.1038/nchembio718] [PMID: 16408018]
[57]
Feng, B.Y.; Shoichet, B.K. Synergy and antagonism of promiscuous inhibition in multiple-compound mixtures. J. Med. Chem., 2006, 49(7), 2151-2154.
[http://dx.doi.org/10.1021/jm060029z] [PMID: 16570910]
[58]
Metz, J.T.; Huth, J.R.; Hajduk, P.J. Enhancement of chemical rules for predicting compound reactivity towards protein thiol groups. J. Comput. Aided Mol. Des., 2007, 21(1-3), 139-144.
[http://dx.doi.org/10.1007/s10822-007-9109-z] [PMID: 17340041]
[59]
Huth, J.R.; Song, D.; Mendoza, R.R.; Black-Schaefer, C.L.; Mack, J.C.; Dorwin, S.A.; Ladror, U.S.; Severin, J.M.; Walter, K.A.; Bartley, D.M.; Hajduk, P.J. Toxicological evaluation of thiol-reactive compounds identified using a la assay to detect reactive molecules by nuclear magnetic resonance. Chem. Res. Toxicol., 2007, 20(12), 1752-1759.
[http://dx.doi.org/10.1021/tx700319t] [PMID: 18001056]
[60]
Baell, J.; Walters, M.A. Chemistry: Chemical con artists foil drug discovery. Nature, 2014, 513(7519), 481-483.
[http://dx.doi.org/10.1038/513481a] [PMID: 25254460]
[61]
Dahlin, J.L.; Walters, M.A. The essential roles of chemistry in high-throughput screening triage. Future Med. Chem., 2014, 6(11), 1265-1290.
[http://dx.doi.org/10.4155/fmc.14.60] [PMID: 25163000]
[62]
Pouliot, M.; Jeanmart, S. Pan Assay Interference Compounds (PAINS) and other promiscuous compounds in antifungal research. J. Med. Chem., 2016, 59(2), 497-503.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00361] [PMID: 26313340]
[63]
Cheng, F.; Li, W.; Zhou, Y.; Shen, J.; Wu, Z.; Liu, G.; Lee, P.W.; Tang, Y. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J. Chem. Inf. Model., 2012, 52(11), 3099-3105.
[http://dx.doi.org/10.1021/ci300367a] [PMID: 23092397]
[64]
Mohareb, R.M.; Abdallah, A.E.M.; Abelaziz, M.A. New approaches for the synthesis of pyrazole, thiophene, thieno[2,3-b]pyridine, and thiazole derivatives together with their anti-tumor evaluations. Med. Chem. Res., 2014, 23, 564-579.
[http://dx.doi.org/10.1007/s00044-013-0664-7]
[65]
Mohareb, R.M.; Wardakhan, W.W.; Hamid, F.I. Synthesis and cytotoxicity of fused thiophene and pyrazole derivatives derived from 2-N-acetyl-3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene. Med. Chem. Res., 2015, 24, 2043-2054.
[http://dx.doi.org/10.1007/s00044-014-1273-9]
[66]
Mohareb, R.M.; Zaki, M.Y.; Abbas, N.S. Synthesis, anti-inflammatory and anti-ulcer evaluations of thiazole, thiophene, pyridine and pyran derivatives derived from androstenedione. Steroids, 2015, 98, 80-91.
[http://dx.doi.org/10.1016/j.steroids.2015.03.001] [PMID: 25759119]
[67]
Mohareb, R.M.; Al-Omran, F.; Ibrahim, R.A. The uses of cyclohexan-1,4-dione for the synthesis of thiophene derivatives as new anti-proliferative, prostate anticancer, c-Met and tyrosine kinase inhibitors. Med. Chem. Res., 2018, 27, 618-633.
[http://dx.doi.org/10.1007/s00044-017-2087-3]
[68]
Bartolomeu, A.A.; Brocksom, T.J.; Filho, L.C.S.; Oliveira, K.T. Multicomponent reactions mediated by NbCl5 for the synthesis of phthalonitrile-quinoline dyads: Methodology, scope, mechanistic insights and applications in phthalocyanine synthesis. Dyes Pigments, 2018, 151, 391-402.
[http://dx.doi.org/10.1016/j.dyepig.2017.12.065]
[69]
Oshiro, P.B.; Lima, S.S.G.; Menezes, M.L.; Filho, L.C.S. Synthesis of 4H-chromenes promoted by NbCl5 through multicomponent reaction. Tetrahedron Lett., 2015, 56, 4476-4479.
[http://dx.doi.org/10.1016/j.tetlet.2015.05.099]
[70]
Filho, J.F.A.; Lemos, B.C.; Souza, A.S.; Pinheiro, S.; Greco, S.J. Multicomponent Mannich reactions: General aspects, methodologies and applications. Tetrahedron, 2017, 73, 6977-7004.
[http://dx.doi.org/10.1016/j.tet.2017.10.063]
[71]
Santos, W.H.; Filho, L.C.S. New method for the synthesis of chromeno [4,3-b] chromene derivatives via multicomponent reaction promoted by niobium pentachloride. Tetrahedron Lett., 2017, 58, 894-897.
[http://dx.doi.org/10.1016/j.tetlet.2017.01.062]
[72]
Zakeri, M.; Nasef, M.M.; Abouzari-Lotf, E.; Moharami, A.; Heravi, M.M. Sustainable alternative protocols for the multicomponent synthesis of spiro-4H-pyrans catalyzed by 4-dimethylaminopyridine. J. Induct. Engin. Chem., 2015, 29, 273-281.
[http://dx.doi.org/10.1016/j.jiec.2015.03.035]
[73]
Tabassum, S.; Govindaraju, S.; Khan, R.U.; Pasha, M.A. Ultrasound mediated, iodine catalyzed green synthesis of novel 2-amino-3-cyano-4H-pyran derivatives. Ultrason. Sonochem., 2015, 24, 1-7.
[http://dx.doi.org/10.1016/j.ultsonch.2014.12.006] [PMID: 25557792]
[74]
El-Sayed, N.N.E.; Abdelaziz, M.A.; Wardakhan, W.W.; Mohareb, R.M. The Knoevenagel reaction of cyanoacetylhydrazine with pregnenolone: Synthesis of thiophene, thieno[2,3-d]pyrimidine, 1,2,4-triazole, pyran and pyridine derivatives with anti-inflammatory and anti-ulcer activities. Steroids, 2016, 107, 98-111.
[http://dx.doi.org/10.1016/j.steroids.2015.12.023] [PMID: 26772772]

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