Synthetic Approaches of Pyrazolyl Quinolines

Author(s): Rizk E. Khidre*, Ibrahim Ali M. Radini, Diaa A. Ibrahim

Journal Name: Mini-Reviews in Organic Chemistry

Volume 16 , Issue 4 , 2019

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Graphical Abstract:


This review article represents a survey of the synthetic strategies leading to pyrazolyl quinolines. The synthetic methods are divided into two main groups based on the type of starting reagents: 1) From quinoline ring onto a pyrazole scaffold, 2) From pyrazole ring onto a quinoline scaffold. Also, some medical applications of pyrazolyl quinoline derivatives are mentioned such as anticancer, cell proliferative disorder, glucose transport inhibitors, anti-inflammatory, and inhibitors of leukotriene production for the treatment of cardiovascular. The main purpose of this review is to present a survey of the literature on the synthetic approaches of pyrazolyl quinolines and provide useful and up-to-date data for organic and medicinal chemist since such compound has not been previously reviewed.

Keywords: Pyrazole, quinoline, pyrazolyl quinolones, heterocyclic compounds, carbaldehyde, pyrazole ring.

Gomtsyan, A. Heterocycles in drugs and drug discovery. Chem. Heterocycl. Compd., 2012, 48, 7-10.
Pozharsky, A.F.; Soldatenkov, A.T.; Katritzky, A.R. Heterocycles in life and society: An introduction to heterocyclic chemistry, biochemistry and applications. Heterocycles in Life and Society; JohnWiley: Chichester, 2011.
Abdel-Wahab, B.F.; Khidre, R.E.; Farahat, A.A.; El-Ahl, A.A.S. 2-Chloroquinoline-3-carbaldehydes: Synthesis, reactions and applications. ARKIVOC, 2012, 2012(i), 211-276.
Abdou, W.M.; Khidre, R.E.; Kamel, A.A. Elaborating on efficient anti-proliferation agents of cancer cells and anti-inflammatory-based n-bisphosphonic acids. Archiv. Der. Pharm. Chem. Life Sci., 2012, 345, 123-136.
Abdou, W.M.; Khidre, R.E.; Shaddy, A.A. Synthesis of tetrazoloquinoline-based mono-and biphosphonate esters as potent anti-inflammatory agents. J. Heterocycl. Chem., 2013, 50, 33-41.
Ibrahim, A.M.R.; Elsheikh, T.M.Y.; El-Telbani, E.M.; Khidre, R.E. New potential antimalarial agents: Design, synthesis, and biological evaluation of some novel quinoline derivatives as antimalarial agents. Molecules, 2016, 7, 909.
Khidre, R.E.; Abdel-Wahab, B.F.; Badria, F.A.R. New quinoline-based compounds for analgesic and anti-inflammatory evaluation. Lett. Drug Des. Discov., 2011, 8, 640-648.
Polanski, J.; Niedbala, H.; Musiol, R.; Podeszwa, B.; Tabak, D.; Palka, A.; Mencel, A.; Finster, J.; Mouscadet, J.F.; Le Bret, M. 5-Hydroxy-6-quinaldic acid as a novel molecular scaffold for HIV-1 integrase inhibitors. Lett. Drug Design . Disc., 2006, 3, 175-178.
Polanski, J.; Niedbala, H.; Musiol, R.; Podeszwa, B.; Tabak, D.; Palka, A.; Mencel, A.; Mouscadet, J.F.; Le Bret, M. Fragment based approach for the investigation of HIV-1 integrase inhibition. Lett. Drug Des. Disc., 2007, 4, 99-105.
Ulven, T.; Little, P.B.; Receveur, J.M.; Frimurer, T.M.; Rist, O.; Nørregaard, P.K.; Hogberg, T. 6-Acylamino-2-amino-4-methyl-quinolines as potent melanin-concentrating hormone 1 receptor antagonists: Structure-activity exploration of eastern and western parts. Bioorg. Med. Chem. Lett., 2006, 16, 1070-1075.
Arienzo, R.; Clark, D.E.; Cramp, S.; Daly, S.; Dyke, H.J.; Lockey, P.; Norman, D.; Roach, A.G.; Stuttle, K.; Tomlinson, M.; Wong, M.; Wren, S.P. Structure-activity relationships of a novel series of Melanin-Concentrating Hormone (MCH) receptor antagonists. Bioorg. Med. Chem. Lett., 2004, 14, 4099-4102.
Zhang, X.; Shetty, A.S.; Jenekhe, S.A. Electroluminescence and photophysical properties of polyquinolines. Macromolecules, 1999, 32, 7422-7429.
Jenekhe, S.A.; Lu, L.; Alam, M.M. New conjugated polymers with donor-acceptor architectures: Synthesis and photophysics of carbazole-quinoline and phenothiazine-quinoline copolymers and oligomers exhibiting large intramolecular charge transfer. Macromolecules, 2001, 34, 7315-7324.
Abdel Aziz, M.; Gamal El-Din, A.; Abuo-Rahma, A.H.A. Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities. Eur. J. Med. Chem., 2005, 44, 3480-3487.
Dinesha, V.S.; Priya, B.K.; Pai, K.S.R.; Naveen, S.; Lokanath, N.K.; Nagaraja, G.K. Synthesis and pharmacological evaluation of some new fluorine containing hydroxypyrazolines as potential anticancer and antioxidant agents. Eur. J. Med. Chem., 2015, 104, 25-32.
Bandgar, B.P.; Gawande, S.S.; Bodade, R.G. Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory, antioxidant and antimicrobial agents. Bioorg. Med. Chem., 2009, 17, 8168-8173.
a)Lv, P.C.; Li, H.Q.; Sun, J.; Zhou, Y.; Zhu, H.L. Synthesis and biological evaluation of pyrazole derivatives containing thiourea skeleton as anticancer agents. Bioorg. Med. Chem., 2010, 18, 4606-4614.
b)Aydın, S.; Kaushik-Basu, N.; Özbaş-Turan, S.; Akbuğa, J.; Tiber, P.M.; Orun, O.; Gurukumar, K.R.; Basu, A.; Küçükgüzel, G.Ş. Synthesis of 1-aroyl-3,5-dimethyl-1H-pyrazoles as anti-HCV and anticancer agents. Lett. Drug Design . Disc., 2014, 11(2), 121-131.
Radini, I.A.M.; Khidre, R.E.; El-Telbani, E.M. Synthesis and antimicrobial evaluation of new pyrazoline and pyrazolinyl thiazole derivatives bearing tetrazolo[1,5-a]quinoline moiety. Lett. Drug Design . Disc., 2016, 13(9), 921-931.
Altıntop, M.D.; Abu Mohsen, U.; Karaca, H.; Canturk, Z.; Ozdemir, A. Synthesis and evaluation of bis-pyrazoline derivatives as potential antimicrobial agents. Lett. Drug Design . Disc., 2014, 11(10), 1199-1203.
Bai, L.S.; Wang, Y.; Liu, X.H.; Zhu, H.L.; Song, B.A. Novel dihydropyrazole derivatives linked with multi(hetero)aromatic ring: Synthesis and antibacterial activity. Chin. Chem. Lett., 2009, 20, 427-430.
Ouyang, G.P.; Cai, X.J.; Chen, Z.; Song, B.A.; Bhadury, P.S.; Yang, S.; Jin, L.H.; Xue, W.; Hu, D.Y.; Zeng, S. Synthesis and antiviral activities of pyrazole derivatives containing an oxime moiety. J. Agric. Food Chem., 2008, 56, 10160-10167.
Ouyang, G.; Chen, Z.; Cai, X.J.; Song, B.A.; Bhadury, P.S.; Yang, S.; Jin, L.H.; Xue, W.; Hu, D.Y.; Zeng, S. Synthesis and antiviral activity of novel pyrazole derivatives containing oxime esters group. Bioorg. Med. Chem., 2008, 16, 9699-9707.
Alagarsamy, V.; Saravanan, G. Synthesis and anticonvulsant activity of novel quinazolin-4(3H)-one derived pyrazole analogs. Med. Chem. Res., 2013, 22, 1711.
Song, H.J.; Liu, Y.X.; Xiong, L.X.; Li, Y.; Yang, N.; Wang, Q. Design, synthesis, and insecticidal evaluation of new pyrazole derivatives containing imine, oxime ether, and dihydroisoxazoline groups based on the inhibitor binding pocket of respiratory complex I. J. Agric. Food Chem., 2013, 61, 8730-8736.
Paitandi, R.P.; Mukhopadhyay, S.; Singh, R.S.; Sharma, V.; Mobin, S.M.; Pandey, D.S. Anticancer activity of Iridium(III) complexes based on a pyrazole-appended quinoline-based BODIPY. Inorganic . Chem., 2017, 56, 12232-12247.
Govaerts, T.C.H.; Weerts, J.E.E.; Leys, C.; Dickens, J.W.J.; Stokbroekx, S.C.M. Preparation of polymorphic and hydrate forms, salts of 6-[difluoro[6-(1-methyl-1H-pyrazol-4-yl)[1,2,4]triazolo[4, 3-b]pyridazin-3-yl]methyl]quinoline for treatment of cell proliferative disorder. US Patent 8,629,144 2014.
Heisler, I.; Mueller, T.; Siebeneicher, H.; Buchmann, B.; Cleve, A.; Guenther, J.; Koppitz, M.; Heroult, M.; Neuhaus, R.; Petrul, H. Npyrazolyl quinolinecarboxamides as glucose transport inhibitors and their preparation. WO Patent 2015,091,428 2015.
Heisler, I.; Mueller, T.; Buchmann, B.; Cleve, A.; Siebeneicher, H.; Koppitz, M.; Schneider, D.; Bauser, M.; Heroult, M.; Neuhaus, R. N-pyrazolyl carboxamides as glucose transport inhibitors and their preparation. PCT Int. Appl., WO Patent 2016,202,898 2016.
Abeywardane, A.; Broadwater, J.; Takahashi, H. Preparation of pyrazolylpyridinylquinolines as inhibitors of leukotriene production for treatment of cardiovascular, inflammatory and other diseases. US Patent 20150,018,333, 2015.
Radini, I.A.M.; Abdel-Wahab, B.F.; Khidre, R.E. Synthetic routes to imidazothiazines. Phosphorus Sulfur Silicon Relat. Elem., 2016, 191, 844-856.
Khidre, R.E.; Abdel-Wahab, B.F. Application of benzoylaceteonitrile in the synthesis of pyridines derivatives. Curr. Org. Chem., 2013, 17(4), 430-445.
Abdel-Wahab, B.F.; Khidre, R.E.; Mohamed, H.A. Synthetic routes to imidazothiadiazines. Phosphorus Sulfur Silicon Relat. Elem., 2015, 190, 1781-1790.
El-Sayed, O.A.; El-Semary, M.; Khalil, M.A. Non-steroidal anti-inflammatory agents: Synthesis of pyrazolyl, pyrazolinyl and pyrimidinyl derivatives of quinoline. Alexandria J. Pharm. Sci., 1996, 10, 43-46.
Radini, I.A.M.; Khidre, R.E.; El-Telbani, E.M. Synthesis and antimicrobial evaluation of new pyrazoline and pyrazolinyl thiazole derivatives bearing tetrazolo[1,5-a]quinoline moiety. Lett. Drug Design . Discov., 2016, 13, 921-931.
Desai, N.C.; Rajpara, K.M.; Joshi, V.V. Synthesis and characterization of some new quinoline based derivatives endowed with broad spectrum antimicrobial potency. Bioorg. Med. Chem. Lett., 2012, 22, 6871-6875.
Lamani, D.S.; Reddy, K.R.; Naik, H.B. An efficient synthesis and DNA binding interaction study of some novel heterocyclic pyrazole quinolines: Potent antimicrobial agents. African J. Pure Appl. Chem., 2010, 4(11), 247-255.
El-Feky, S.A.H.; Abd El-Samii, Z.K.; Osman, N.A.; Lashine, J.; Kamel, M.A.; Thabet, H.K. Synthesis, molecular docking and anti-inflammatory screening of novel quinoline incorporated pyrazole derivatives using the Pfitzinger reaction II. Bioorg. Chem., 2015, 58, 104-116.
Singh, S.P.; Tarar, L.S.; Vaid, R.K.; Elguero, J.; Martinez, A. Reaction of 4-hydrazinoquinolines with diketones: Synthesis and spectroscopy (proton, carbon-13NMR, MS) of some pyrazolylquinolines. J. Heterocycl. Chem., 1989, 26, 733-738.
Scott, F.L.; Crowley, K.M.; Reilly, J. The halogenation of 3,5-dimethyl-1-(2-quinolyl)pyrazole. J. Am. Chem. Soc., 1952, 74, 3444-3445.
Pavan, P.; Subashini, R.; Ethiraj, K.R.; Khan, F.R. Potential anti-bacterial agents: Montmorillonite clay-catalyzed synthesis of novel 2-(3,5-substituted-1Hpyrazol-1-yl)-3-substituted quinolines and their in silico molecular docking studies. RSC Advances, 2014, 4, 58011-58018.
Senthil Kumar, G.; Kaminsky, W.; Rajendra Prasad, K.J. InCl3-promoted synthesis of pyrazolyl-substituted quinolines in green media. Synth. Commun., 2015, 45(15), 1751-1760.
Cunico, W.; Cechinel, C.A.; Bonacorso, H.G.; Martins, M.A.; Zanatta, N.; de Souza, M.V.; Freitas, I.O.; Soares, R.P.; Krettli, A.U. Antimalarial activity of 4-(5-trifluoromethyl-1H-pyrazol-1-yl)-chloroquine analogues. Bioorg. Med. Chem. Lett., 2006, 16(3), 649-653.
Drobnic-Kosorok, M.; Jernejc-Pfundner, K.; Peternel, J.; Stanovnik, B.; Tisler, M. Transformations of some substituted methylene heterocycles with some nucleophiles. J. Heterocycl. Chem., 1976, 13(6), 1279-1282.
Jarenmark, M.; Fredin, L.A.; Hedberg, J.H.; Doverbratt, I.; Persson, P.; Abrahamsson, M. A homoleptic trisbidentate Ru(II) complex of a novel bidentate biheteroaromatic ligand based on quinoline and pyrazole groups: Structural, electrochemical, photophysical, and computational characterization. Inorg. Chem., 2014, 53(24), 12778-12790.
Williams, R.P.; Bauer, V.J.; Safir, S.R. 1-Methyl-4-[5(3)-methyl-3(5)-pyrazolyl]quinolinium iodide: An analog of the hypoglycemic pyrazolylpyridinium salts. J. Med. Chem., 1969, 12(5), 1124-1125.
Hu, L.; Yan, S.; Luo, Z.; Han, X.; Wang, Y.; Wang, Z.; Zeng, C. Design, practical synthesis, and biological evaluation of novel 6-(pyrazolylmethyl)-4-quinoline-3-carboxylic acid derivatives as HIV-1 integrase inhibitors. Molecules, 2012, 17(9), 10652-10666.
Finar, I.L.; Hurlock, R.J. Skraup reaction with aminopyrazoles. J. Chem. Soc., 1958, 3259-3263.
Patel, H.V.; Vyas, K.A.; Fernandes, P.S. Synthesis of substituted 6-(3′,5′-dimethyl-1H-pyrazol-1-yl)quinolines and evaluation of their biological activities. Ind. J. Chem. B, 1990, 29B(9), 836-842.
Thumar, N.J.; Patel, M.P. Synthesis, characterization, and antimicrobial evaluation of carbostyril derivatives of 1H-pyrazole. Saudi Pharm. J., 2011, 19(2), 75-83.
Amol, G.; Chetan, P.; Sahebrao, S.R.; Bhausaheb, K. Synthesis of novel multifluorinated pyrazolone-5-one derivatives via conventional and non-conventional methods. Int. J. Chem., 2010, 2, 206-212.
Jia, Z.; Wei, S.; Zhu, Q. Monoamine oxidase inhibitors: Benzylidene-prop-2-ynyl-amines analogues. Biol. Pharm. Bull., 2010, 33(4), 725-728.
Charris, J.E.; Lobo, G.M.; Camacho, J.; Ferrer, R.; Barazarte, A.; Dominguez, J.N.; Gamboa, N.; Rodrigues, J.R.; Angel, J.E. Synthesis and antimalarial activity of (E) 2-(2′-chloro-3′-quinolinylmethylidene)-5,7-dimethoxyindanones. Lett. Drugs Des. Disc., 2007, 4(1), 49-54.
Kalluraya, B.; Gururaja, R.; Rai, G. One pot reaction: Synthesis, characterization and biological activity of 3-alkyl/aryl-9-substituted 1,2,4-triazolo[3,4-b] [1,3,4]quinolino thiadiazepines. Ind. J. Chem. B, 2003, 42B(1), 211-214.
Nakum, S.D.; Pavagadhi, T.H.; Shah, V.H. A facile generation of cyanopyrans: Synthesis of 2-amino-3-cyano-4-(2′-chloro substituted quinoline-3′-yl/aryl)-5-methyl-7-phenylpyrazolo[5,6-d]-4H-pyrans. Ind J. Heterocycl. Chem., 2002, 12(1), 75-76.

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Article Details

Year: 2019
Published on: 19 April, 2018
Page: [353 - 360]
Pages: 8
DOI: 10.2174/1570193X15666180419142511
Price: $65

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