Recent Progress in Anticancer Agents Incorporating Pyrazole Scaffold

Satbir      Mor; Mohini       Khatri; Ravinder       punia; Suchita       Sindhu
Abstract

Abstract: The search for new anticancer agents is considered a dynamic field of medicinal chemistry. In recent years, the synthesis of compounds with anticancer potential has increased and a large number of structurally varied compounds displaying potent anticancer activities have been published. Pyrazole is an important biologically active scaffold that possesses nearly all types of biological activities. The aim of this review is to collate literature work reported by researchers to provide an overview on in vivo and in vitro anticancer activities of pyrazole based derivatives among the diverse biological activities displayed by them and also to present recent efforts made on this heterocyclic moiety regarding anticancer activities. This review has been driven by the increasing number of publications on this issue, which have been reported in the literature since the end of the 20^th century (from 1995-to date).
Keywords: Pyrazole, anticancer activity, EGFR, CDK inhibitor, anti-proliferation, apoptosis, telomerase.
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[1] 
Rao, B.M.; Ramesh, S.; Bardalai, D.; Rahman, H.; Shaik, H.A. Synthesis, characterization and evaluation of anti-epileptic activity of four new 2-pyrazoline derivatives compounds. Sch. J. App. Med. Sci.,  2013, 1, 20-27.
[2] 
Eicher, T.; Hauptmann, S. The chemistry of heterocycles: Structures, reactions, syntheses, and applications, 2nd ed.; Wiley-VCH GmbH & Co. KGaA:: Weinheim, 2003. 
[http://dx.doi.org/10.1002/352760183X] 
[3] 
Maggio, B.; Raffa, D.; Raimondi, M.V.; Cusimano, M.G.; Plescia, F.; Cascioferro, S.; Cancemi, G.; Lauricella, M.; Carlisi, D.; Daidone, G. Synthesis and antiproliferative activity of new derivatives containing the polycyclic system 5,7:7,13-dimethanopyrazolo[3,4-b]pyrazolo[3′,4′:2,3]azepino[4,5-f]azocine. Eur. J. Med. Chem.,  2014, 72, 1-9.
[http://dx.doi.org/10.1016/j.ejmech.2013.11.016] [PMID: 24333609] 
[4] 
Tantawy, A.S.; Nasr, M.N.A.; El-Sayed, M.A.A.; Tawfik, S.S. Synthesis and antiviral activity of new 3-methyl-1,5-diphenyl-1H-pyrazole derivatives. Med. Chem. Res.,  2012, 21, 4139-4149.
[http://dx.doi.org/10.1007/s00044-011-9960-2] 
[5] 
Lavanya, G.; Mallikarjuna Reddy, L.; Padmavathi, V.; Padmaja, A. Synthesis and antimicrobial activity of (1,4-phenylene)bis(arylsulfonylpyrazoles and isoxazoles). Eur. J. Med. Chem.,  2014, 73, 187-194.
[http://dx.doi.org/10.1016/j.ejmech.2013.11.041] [PMID: 24398288] 
[6] 
Bakavoli, M.; Feizyzadeh, B.; Rahimizadeh, M. Investigation of hydrazine addition to functionalized furans: synthesis of new functionalized 4, 4′-bipyrazole derivatives. Tetrahedron Lett.,  2006, 47, 8965-8968.
[http://dx.doi.org/10.1016/j.tetlet.2006.10.037] 
[7] 
Abdel-Aziz, M. Abuo-Rahma, Gel-D.; Hassan, A.A. Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities. Eur. J. Med. Chem.,  2009, 44(9), 3480-3487.
[http://dx.doi.org/10.1016/j.ejmech.2009.01.032] [PMID: 19268406] 
[8] 
Bonesi, M.; Loizzo, M.R.; Statti, G.A.; Michel, S.; Tillequin, F.; Menichini, F. The synthesis and angiotensin converting enzyme (ACE) inhibitory activity of chalcones and their pyrazole derivatives. Bioorg. Med. Chem. Lett.,  2010, 20(6), 1990-1993.
[http://dx.doi.org/10.1016/j.bmcl.2010.01.113] [PMID: 20167484] 
[9] 
Shabbir, A.; Shahzad, M.; Ali, A. Zia-ur-Rehman, M. Anti-arthritic activity of N′-[(2,4-dihydroxyphenyl)methylidene]-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-1(4H)-yl)acetohydrazide. Eur. J. Pharmacol.,  2014, 738, 263-272.
[http://dx.doi.org/10.1016/j.ejphar.2014.05.045] [PMID: 24943733] 
[10] 
Ahsan, M.J.; Samy, J.G.; Jain, C.B.; Dutt, K.R.; Khalilullah, H.; Nomani, M.S. Discovery of novel antitubercular 1,5-dimethyl-2-phenyl-4-([5-(arylamino)-1,3,4-oxadiazol-2-yl]methylamino)-1,2-dihydro-3H-pyrazol-3-one analogues. Bioorg. Med. Chem. Lett.,  2012, 22(2), 969-972.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.014] [PMID: 22197387] 
[11] 
Aboul-Enein, M.N.; El-Azzouny, A.A.; Attia, M.I.; Maklad, Y.A.; Amin, K.M.; Abdel-Rehim, M.; El-Behairy, M.F. Design and synthesis of novel stiripentol analogues as potential anticonvulsants. Eur. J. Med. Chem.,  2012, 47(1), 360-369.
[http://dx.doi.org/10.1016/j.ejmech.2011.11.004] [PMID: 22118828] 
[12] 
Zaki, R.M.; El-Ossaily, Y.A.; Geies, A.A. A convenient synthesis, reactions and biological studies of some novel selenolo[2,3-c]pyrazole compounds as antimicrobial and anti-inflammatory agents. Med. Chem. Res.,  2016, 25, 893-908.
[http://dx.doi.org/10.1007/s00044-016-1536-8] 
[13] 
Kenchappa, R.; Bodke, Y.D.; Chandrashekar, A.; Sindhe, M.A.; Peethambar, S.K. Synthesis of coumarin derivatives containing pyrazole and indenone rings as potent antioxidant and antihyperglycemic agents. Arab. J. Chem.,  2017, 10, 53895-53906.
[http://dx.doi.org/10.1016/j.arabjc.2014.05.029] 
[14] 
Rizvi, S.U.F.; Siddiqui, H.L.; Johns, M.; Detorio, M.; Schinazi, R.F. Anti-HIV-1 and cytotoxicity studies of piperidyl-thienyl chalcones and their 2-pyrazoline derivatives. Med. Chem. Res.,  2012, 21, 3741-3749.
[http://dx.doi.org/10.1007/s00044-011-9912-x] 
[15] 
Cottineau, B.; Toto, P.; Marot, C.; Pipaud, A.; Chenault, J. Synthesis and hypoglycemic evaluation of substituted pyrazole-4-carboxylic acids. Bioorg. Med. Chem. Lett.,  2002, 12(16), 2105-2108.
[http://dx.doi.org/10.1016/S0960-894X(02)00380-3] [PMID: 12127514] 
[16] 
Pasin, J.S.M.; Ferreira, A.P.O.; Saraiva, A.L.L.; Ratzlaff, V.; Andrighetto, R.; Machado, P.; Marchesan, S.; Zanette, R.A.; Bonacorso, H.G.; Zanatta, N.; Martins, M.A.P.; Ferreira, J.; Mello, C.F. Antipyretic and antioxidant activities of 5-trifluoromethyl-4,5-dihydro-1H-pyrazoles in rats. Braz. J. Med. Biol. Res.,  2010, 43(12), 1193-1202.
[http://dx.doi.org/10.1590/S0100-879X2010007500139] [PMID: 21140097] 
[17] 
Geronikaki, A.; Babaev, E.; Dearden, J.; Dehaen, W.; Filimonov, D.; Galaeva, I.; Krajneva, V.; Lagunin, A.; Macaev, F.; Molodavkin, G.; Poroikov, V.; Pogrebnoi, S.; Saloutin, V.; Stepanchikova, A.; Stingaci, E.; Tkach, N.; Vlad, L.; Voronina, T. Design, synthesis, computational and biological evaluation of new anxiolytics. Bioorg. Med. Chem.,  2004, 12(24), 6559-6568.
[http://dx.doi.org/10.1016/j.bmc.2004.09.016] [PMID: 15556772] 
[18] 
Fustero, S.; Sánchez-Roselló, M.; Barrio, P.; Simón-Fuentes, A. From 2000 to mid-2010: a fruitful decade for the synthesis of pyrazoles. Chem. Rev.,  2011, 111(11), 6984-7034.
[http://dx.doi.org/10.1021/cr2000459] [PMID: 21806021] 
[19] 
Frank, A.O.; Feldkamp, M.D.; Kennedy, J.P.; Waterson, A.G.; Pelz, N.F.; Patrone, J.D.; Vangamudi, B.; Camper, D.V.; Rossanese, O.W.; Chazin, W.J.; Fesik, S.W. Discovery of a potent inhibitor of replication protein a protein-protein interactions using a fragment-linking approach. J. Med. Chem.,  2013, 56(22), 9242-9250.
[http://dx.doi.org/10.1021/jm401333u] [PMID: 24147804] 
[20] 
Ahsan, M.J.; Khalilullah, H.; Yasmin, S.; Jadav, S.S.; Govindasamy, J. Synthesis, characterisation, and in vitro anticancer activity of curcumin analogues bearing pyrazole/pyrimidine ring targeting EGFR tyrosine kinase. BioMed Res. Int.,  2013, 2013, 239354.
[http://dx.doi.org/10.1155/2013/239354] [PMID: 24089667] 
[21] 
Kibria, G.; Hatakeyama, H.; Harashima, H. Cancer multidrug resistance: mechanisms involved and strategies for circumvention using a drug delivery system. Arch. Pharm. Res.,  2014, 37(1), 4-15.
[http://dx.doi.org/10.1007/s12272-013-0276-2] [PMID: 24272889] 
[22] 
Richard, D.J.; Verheijen, J.C.; Curran, K.; Kaplan, J.; Toral-Barza, L.; Hollander, I.; Lucas, J.; Yu, K.; Zask, A. Incorporation of water-solubilizing groups in pyrazolopyrimidine mTOR inhibitors: discovery of highly potent and selective analogs with improved human microsomal stability. Bioorg. Med. Chem. Lett.,  2009, 19(24), 6830-6835.
[http://dx.doi.org/10.1016/j.bmcl.2009.10.096] [PMID: 19896845] 
[23] 
Traxler, P.; Bold, G.; Frei, J.; Lang, M.; Lydon, N.; Mett, H.; Buchdunger, E.; Meyer, T.; Mueller, M.; Furet, P. Use of a pharmacophore model for the design of EGF-R tyrosine kinase inhibitors: 4-(phenylamino)pyrazolo[3,4-d]pyrimidines. J. Med. Chem.,  1997, 40(22), 3601-3616.
[http://dx.doi.org/10.1021/jm970124v] [PMID: 9357527] 
[24] 
Manetti, F.; Santucci, A.; Locatelli, G.A.; Maga, G.; Spreafico, A.; Serchi, T.; Orlandini, M.; Bernardini, G.; Caradonna, N.P.; Spallarossa, A.; Brullo, C.; Schenone, S.; Bruno, O.; Ranise, A.; Bondavalli, F.; Hoffmann, O.; Bologna, M.; Angelucci, A.; Botta, M. Identification of a novel pyrazolo[3,4-d]pyrimidine able to inhibit cell proliferation of a human osteogenic sarcoma in vitro and in a xenograft model in mice. J. Med. Chem.,  2007, 50(23), 5579-5588.
[http://dx.doi.org/10.1021/jm061449r] [PMID: 17929792] 
[25] 
Elguero, J.; Goya, P.; Jagerovic, N.; Silva, A.M.S. Pyrazoles as drugs: facts and fantasies. Targets Heterocycl. Syst,  2002, 6, 52-98.
[26] 
Wei, F.; Zhao, B.X.; Huang, B.; Zhang, L.; Sun, C.H.; Dong, W.L.; Shin, D.S.; Miao, J.Y. Design, synthesis, and preliminary biological evaluation of novel ethyl 1-(2′-hydroxy-3′-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate. Bioorg. Med. Chem. Lett.,  2006, 16(24), 6342-6347.
[http://dx.doi.org/10.1016/j.bmcl.2006.09.008] [PMID: 17000107] 
[27] 
Bennani, F.E.; Doudach, L.; Cherrah, Y.; Ramli, Y.; Karrouchi, K.; Ansar, M.; Faouzi, M.E.A. Overview of recent developments of pyrazole derivatives as an anticancer agent in different cell line. Bioorg. Chem.,  2020, 97, 103470-103618.
[http://dx.doi.org/10.1016/j.bioorg.2019.103470] [PMID: 32120072] 
[28] 
Gordaliza, M.; del Corral, J.M.; Castro, M.A.; López-Vázquez, M.L.; San Feliciano, A.; García-Grávalos, M.D.; Carpy, A. Synthesis and evaluation of pyrazolignans. A new class of cytotoxic agents. Bioorg. Med. Chem.,  1995, 3(9), 1203-1210.
[http://dx.doi.org/10.1016/0968-0896(95)00091-T] [PMID: 8564411] 
[29] 
Broomhead, J.A.; Camm, G.; Sterns, M.; Webster, L. Dinuclear complexes of first transition series metals with 4,4′-dipyrazolylmethane: characterisation, DNA binding and anticancer properties. Inorg. Chim. Acta,  1998, 271, 151-159.
[http://dx.doi.org/10.1016/S0020-1693(97)05955-0] 
[30] 
Bu, X.; Chen, J.; Deady, L.W.; Denny, W.A. Synthesis and cytotoxicity of potential anticancer derivatives of pyrazolo[3,4,5-kl] acridine and indolo[2,3-a]acridine. Tetrahedron,  2002, 58, 175-181.
[http://dx.doi.org/10.1016/S0040-4020(01)01119-X] 
[31] 
Ortega, M.A.; Montoya, M.E.; Zarranz, B.; Jaso, A.; Aldana, I.; Leclerc, S.; Meijer, L.; Monge, A. Pyrazolo[3,4-b]quinoxalines. A new class of cyclin-dependent kinases inhibitors. Bioorg. Med. Chem.,  2002, 10(7), 2177-2184.
[http://dx.doi.org/10.1016/S0968-0896(02)00069-X] [PMID: 11983514] 
[32] 
Rostom, S.A.; Shalaby, M.A.; El-Demellawy, M.A. Polysubstituted pyrazoles, part 5. Synthesis of new 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazole-3-carboxylic acid hydrazide analogs and some derived ring systems. A novel class of potential antitumor and anti-HCV agents. Eur. J. Med. Chem.,  2003, 38(11-12), 959-974.
[http://dx.doi.org/10.1016/j.ejmech.2003.08.003] [PMID: 14642328] 
[33] 
Moravcová, D.; Krystof, V.; Havlícek, L.; Moravec, J.; Lenobel, R.; Strnad, M. Pyrazolo[4,3-d]pyrimidines as new generation of cyclin-dependent kinase inhibitors. Bioorg. Med. Chem. Lett.,  2003, 13(18), 2989-2992.
[http://dx.doi.org/10.1016/S0960-894X(03)00631-0] [PMID: 12941318] 
[34] 
Schenone, S.; Bruno, O.; Bondavalli, F.; Ranise, A.; Mosti, L.; Menozzi, G.; Fossa, P.; Donnini, S.; Santoro, A.; Ziche, M.; Manetti, F.; Botta, M. Antiproliferative activity of new 1-aryl-4-amino-1H-pyrazolo[3,4-d]pyrimidine derivatives toward the human epidermoid carcinoma A431 cell line. Eur. J. Med. Chem.,  2004, 39(11), 939-946.
[http://dx.doi.org/10.1016/j.ejmech.2004.07.010] [PMID: 15501543] 
[35] 
Yue, E.W.; DiMeo, S.V.; Higley, C.A.; Markwalder, J.A.; Burton, C.R.; Benfield, P.A.; Grafstrom, R.H.; Cox, S.; Muckelbauer, J.K.; Smallwood, A.M.; Chen, H.; Chang, C.H.; Trainor, G.L.; Seitz, S.P. Synthesis and evaluation of indenopyrazoles as cyclin-dependent kinase inhibitors. Part 4: Heterocycles at C3. Bioorg. Med. Chem. Lett.,  2004, 14(2), 343-346.
[http://dx.doi.org/10.1016/j.bmcl.2003.11.008] [PMID: 14698155] 
[36] 
Daidone, G.; Maggio, B.; Raffa, D.; Plescia, S.; Schillaci, D.; Valeria Raimondi, M. Synthesis and in vitro antileukemic activity of new 4-triazenopyrazole derivatives. Farmaco,  2004, 59(5), 413-417.
[http://dx.doi.org/10.1016/j.farmac.2004.01.016] [PMID: 15120321] 
[37] 
Budzisz, E.; Krajewska, U.; Rozalski, M.; Szulawska, A.; Czyz, M.; Nawrot, B. Biological evaluation of novel Pt(II) and Pd(II) complexes with pyrazole-containing ligands. Eur. J. Pharmacol.,  2004, 502(1-2), 59-65.
[http://dx.doi.org/10.1016/j.ejphar.2004.08.053] [PMID: 15464090] 
[38] 
Fancelli, D.; Berta, D.; Bindi, S.; Cameron, A.; Cappella, P.; Carpinelli, P.; Catana, C.; Forte, B.; Giordano, P.; Giorgini, M.L.; Mantegani, S.; Marsiglio, A.; Meroni, M.; Moll, J.; Pittalà, V.; Roletto, F.; Severino, D.; Soncini, C.; Storici, P.; Tonani, R.; Varasi, M.; Vulpetti, A.; Vianello, P. Potent and selective Aurora inhibitors identified by the expansion of a novel scaffold for protein kinase inhibition. J. Med. Chem.,  2005, 48(8), 3080-3084.
[http://dx.doi.org/10.1021/jm049076m] [PMID: 15828847] 
[39] 
Wei, F.; Zhao, B.; Huang, B.; Zhang, L.; Sun, C.H.; Dong, W.L.; Shin, D.S.; Miao, J.Y. Design, synthesis and preliminary biological evaluation of novel ethyl 1-(2ˈ- hydroxy-3ˈ-aroxypropyl)-3-aryl-1H-pyrazole-5-carboxylate). Bioorg. Med. Chem. Lett.,  2006, 16, 6342-6347.
[http://dx.doi.org/10.1016/j.bmcl.2006.09.008] [PMID: 17000107] 
[40] 
Akritopoulou-Zanze, I.; Albert, D.H.; Bousquet, P.F.; Cunha, G.A.; Harris, C.M.; Moskey, M.; Dinges, J.; Stewart, K.D.; Sowin, T.J. Synthesis and biological evaluation of 5-substituted 1,4-dihydroindeno[1,2-c]pyrazoles as multitargeted receptor tyrosine kinase inhibitors. Bioorg. Med. Chem. Lett.,  2007, 17(11), 3136-3140.
[http://dx.doi.org/10.1016/j.bmcl.2007.03.031] [PMID: 17391959] 
[41] 
Lin, R.; Chiu, G.; Yu, Y.; Connolly, P.J.; Li, S.; Lu, Y.; Adams, M.; Fuentes-Pesquera, A.R.; Emanuel, S.L.; Greenberger, L.M. Design, synthesis, and evaluation of 3,4-disubstituted pyrazole analogues as anti-tumor CDK inhibitors. Bioorg. Med. Chem. Lett.,  2007, 17(16), 4557-4561.
[http://dx.doi.org/10.1016/j.bmcl.2007.05.092] [PMID: 17574416] 
[42] 
Tao, Z.F.; Li, G.; Tong, Y.; Chen, Z.; Merta, P.; Kovar, P.; Zhang, H.; Rosenberg, S.H.; Sham, H.L.; Sowin, T.J.; Lin, N.H. Synthesis and biological evaluation of 4′-(6,7-disubstituted-2,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-biphenyl-4-ol as potent Chk1 inhibitors. Bioorg. Med. Chem. Lett.,  2007, 17(15), 4308-4315.
[http://dx.doi.org/10.1016/j.bmcl.2007.05.027] [PMID: 17544271] 
[43] 
Tao, Z.F.; Li, G.; Tong, Y.; Stewart, K.D.; Chen, Z.; Bui, M.H.; Merta, P.; Park, C.; Kovar, P.; Zhang, H.; Sham, H.L.; Rosenberg, S.H.; Sowin, T.J.; Lin, N.H. Discovery of 4ˈ-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles and 4ˈ-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-pyridine-2ˈ-carbonitriles as potent Check point Kinase 1(ChK1) inhibitors. Bioorg. Med. Chem. Lett.,  2007, 17, 5944-5951.
[http://dx.doi.org/10.1016/j.bmcl.2007.07.102] [PMID: 17827013] 
[44] 
Fan, C.D.; Zhao, B.X.; Wei, F.; Zhang, G.H.; Dong, W.L.; Miao, J.Y. Synthesis and discovery of autophagy inducers for A549 and H460 lung cancer cells, novel 1-(2ˈ-hydroxy-3ˈ-aroxypropyl)-3-aryl-1H-pyrazole-5-carbohydrazide derivatives. Bioorg. Med. Chem. Lett.,  2008, 18, 3860-3864.
[http://dx.doi.org/10.1016/j.bmcl.2008.06.058] [PMID: 18595694] 
[45] 
Zhang, J.H.; Fan, C.D.; Zhao, B.X.; Shin, D.S.; Dong, W.L.; Xie, Y.S.; Miao, J.Y. Synthesis and preliminary biological evaluation of novel pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives as potential agents against A549 lung cancer cells. Bioorg. Med. Chem.,  2008, 16(24), 10165-10171.
[http://dx.doi.org/10.1016/j.bmc.2008.10.066] [PMID: 19013820] 
[46] 
Pan, X.H.; Liu, X.; Zhao, B.X.; Xie, Y.S.; Shin, D.S.; Zhang, S.L.; Zhao, J.; Miao, J.Y. 5-Alkyl-2-ferrocenyl-6,7-dihydropyrazolo[1,5-a]pyrazin-4(5H)-one derivatives inhibit growth of lung cancer A549 cell by inducing apoptosis. Bioorg. Med. Chem.,  2008, 16(20), 9093-9100.
[http://dx.doi.org/10.1016/j.bmc.2008.09.046] [PMID: 18829332] 
[47] 
Zhang, H.Z.; Claassen, G.; Crogran-Grundy, C.; Tseng, B.; Drewe, J.; Cai, S.X. Discovery and structure-activity relationship of N-phenyl-1H-pyrazolo[3,4-b]quinolin-4-amines as a new series of potent apoptosis inducers. Bioorg. Med. Chem.,  2008, 16(1), 222-231.
[http://dx.doi.org/10.1016/j.bmc.2007.09.046] [PMID: 17950608] 
[48] 
Xia, Y.; Fan, C.D.; Zhao, B.X.; Zhao, J.; Shin, D.S.; Miao, J.Y. Synthesis and structure-activity relationships of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone derivatives as potential agents against A549 lung cancer cells. Eur. J. Med. Chem.,  2008, 43(11), 2347-2353.
[http://dx.doi.org/10.1016/j.ejmech.2008.01.021] [PMID: 18313806] 
[49] 
Usui, T.; Ban, H.S.; Kawada, J.; Hirokawa, T.; Nakamura, H. Discovery of indenopyrazoles as EGFR and VEGFR-2 tyrosine kinase inhibitors by in silico high-throughput screening. Bioorg. Med. Chem. Lett.,  2008, 18(1), 285-288.
[http://dx.doi.org/10.1016/j.bmcl.2007.10.084] [PMID: 17983745] 
[50] 
Saulnier, M.G.; Frennesson, D.B.; Wittman, M.D.; Zimmermann, K.; Velaparthi, U.; Langley, D.R.; Struzynski, C.; Sang, X.; Carboni, J.; Li, A.; Greer, A.; Yang, Z.; Balimane, P.; Gottardis, M.; Attar, R.; Vyas, D. 2-(1H-Imidazol-4-yl)ethanamine and 2-(1H-pyrazol-1-yl)ethanamine side chain variants of the IGF-1R inhibitor BMS-536924. Bioorg. Med. Chem. Lett.,  2008, 18(5), 1702-1707.
[http://dx.doi.org/10.1016/j.bmcl.2008.01.049] [PMID: 18258427] 
[51] 
Ding, X.L.; Zhang, H.Y.; Qi, L.; Zhao, B.X.; Lian, S.; Lv, H.S.; Miao, J.Y. Synthesis of novel pyrazole carboxamide derivatives and discovery of modulators for apoptosis or autophagy in A549 lung cancer cells. Bioorg. Med. Chem. Lett.,  2009, 19(18), 5325-5328.
[http://dx.doi.org/10.1016/j.bmcl.2009.07.131] [PMID: 19683442] 
[52] 
Lian, S.; Su, H.; Zhao, B.X.; Liu, W.Y.; Zheng, L.W.; Miao, J.Y. Synthesis and discovery of pyrazole-5-carbohydrazide N-glycosides as inducer of autophagy in A549 lung cancer cells. Bioorg. Med. Chem.,  2009, 17(20), 7085-7092.
[http://dx.doi.org/10.1016/j.bmc.2009.09.004] [PMID: 19773174] 
[53] 
Zheng, L.W.; Wu, L.L.; Zhao, B.X.; Dong, W.L.; Miao, J.Y. Synthesis of novel substituted pyrazole-5-carbohydrazide hydrazone derivatives and discovery of a potent apoptosis inducer in A549 lung cancer cells. Bioorg. Med. Chem.,  2009, 17(5), 1957-1962.
[http://dx.doi.org/10.1016/j.bmc.2009.01.037] [PMID: 19217789] 
[54] 
Joksovic, M.D.; Markovic, V.; Juranic, Z.D.; Stanojkovic, T.; Jovanovic, L.S.; Damljanovic, I.S.; Szecsenyi, K.M.; Todorovic, N.; Trifunovic, S.; Vukicevic, R.D. Synthesis, characterization and anti-tumor activity of novel N-substituted α-amino acids containing ferrocenyl pyrazole-moiety. J. Organomet. Chem.,  2009, 694, 3935-3942.
[http://dx.doi.org/10.1016/j.jorganchem.2009.08.013] 
[55] 
El-Deeb, I.M.; Lee, S.H. Design and synthesis of new potent anticancer pyrazoles with high FLT3 kinase inhibitory selectivity. Bioorg. Med. Chem.,  2010, 18(11), 3961-3973.
[http://dx.doi.org/10.1016/j.bmc.2010.04.029] [PMID: 20472440] 
[56] 
Brasca, M.G.; Albanese, C.; Alzani, R.; Amici, R.; Avanzi, N.; Ballinari, D.; Bischoff, J.; Borghi, D.; Casale, E.; Croci, V.; Fiorentini, F.; Isacchi, A.; Mercurio, C.; Nesi, M.; Orsini, P.; Pastori, W.; Pesenti, E.; Pevarello, P.; Roussel, P.; Varasi, M.; Volpi, D.; Vulpetti, A.; Ciomei, M. Optimization of 6,6-dimethyl pyrrolo[3,4-c]pyrazoles: Identification of PHA-793887, a potent CDK inhibitor suitable for intravenous dosing. Bioorg. Med. Chem.,  2010, 18(5), 1844-1853.
[http://dx.doi.org/10.1016/j.bmc.2010.01.042] [PMID: 20153204] 
[57] 
Bandgar, B.P.; Totre, J.V.; Gawande, S.S.; Khobragade, C.N.; Warangkar, S.C.; Kadam, P.D. Synthesis of novel 3,5-diaryl pyrazole derivatives using combinatorial chemistry as inhibitors of tyrosinase as well as potent anticancer, anti-inflammatory agents. Bioorg. Med. Chem.,  2010, 18(16), 6149-6155.
[http://dx.doi.org/10.1016/j.bmc.2010.06.046] [PMID: 20638287] 
[58] 
Congiu, C.; Onnis, V.; Vesci, L.; Castorina, M.; Pisano, C. Synthesis and in vitro antitumor activity of new 4,5-dihydropyrazole derivatives. Bioorg. Med. Chem.,  2010, 18(17), 6238-6248.
[http://dx.doi.org/10.1016/j.bmc.2010.07.037] [PMID: 20702096] 
[59] 
Bindi, S.; Fancelli, D.; Alli, C.; Berta, D.; Bertrand, J.A.; Cameron, A.D.; Cappella, P.; Carpinelli, P.; Cervi, G.; Croci, V.; D’Anello, M.; Forte, B.; Giorgini, M.L.; Marsiglio, A.; Moll, J.; Pesenti, E.; Pittalà, V.; Pulici, M.; Riccardi-Sirtori, F.; Roletto, F.; Soncini, C.; Storici, P.; Varasi, M.; Volpi, D.; Zugnoni, P.; Vianello, P. Thieno[3,2-c]pyrazoles: a novel class of Aurora inhibitors with favorable antitumor activity. Bioorg. Med. Chem.,  2010, 18(19), 7113-7120.
[http://dx.doi.org/10.1016/j.bmc.2010.07.048] [PMID: 20817473] 
[60] 
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(13), 4606-4614.
[http://dx.doi.org/10.1016/j.bmc.2010.05.034] [PMID: 20627597] 
[61] 
Cheng, K.M.; Huang, Y.Y.; Huang, J.J.; Kaneko, K.; Kimura, M.; Takayama, H.; Juang, S.H.; Wong, F.F. Synthesis and antiproliferative evaluation of N,N-disubstituted-N'-[1-aryl-1H-pyrazol-5-yl]-methnimidamides. Bioorg. Med. Chem. Lett.,  2010, 20(22), 6781-6784.
[http://dx.doi.org/10.1016/j.bmcl.2010.08.133] [PMID: 20855206] 
[62] 
Rostom, S.A.F. Polysubstituted pyrazoles, part 6. Synthesis of some 1-(4-chlorophenyl)-4-hydroxy-1H-pyrazol-3-carbonyl derivatives linked to nitrogenous heterocyclic ring systems as potential antitumor agents. Bioorg. Med. Chem.,  2010, 18(7), 2767-2776.
[http://dx.doi.org/10.1016/j.bmc.2010.02.006] [PMID: 20207545] 
[63] 
Shi, J.; Xu, G.; Zhu, W.; Ye, H.; Yang, S.; Luo, Y.; Han, J.; Yang, J.; Li, R.; Wei, Y.; Chen, L. Design and synthesis of 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles and pyrazolo[3,4-b]pyridines for Aurora-A kinase inhibitors. Bioorg. Med. Chem. Lett.,  2010, 20(14), 4273-4278.
[http://dx.doi.org/10.1016/j.bmcl.2010.04.083] [PMID: 20621733] 
[64] 
Insuasty, B.; Tigreros, A.; Orozco, F.; Quiroga, J.; Abonía, R.; Nogueras, M.; Sanchez, A.; Cobo, J. Synthesis of novel pyrazolic analogues of chalcones and their 3-aryl-4-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)-1-phenyl-1H-pyrazole derivatives as potential antitumor agents. Bioorg. Med. Chem.,  2010, 18(14), 4965-4974.
[http://dx.doi.org/10.1016/j.bmc.2010.06.013] [PMID: 20594863] 
[65] 
Zheng, L.W.; Li, Y.; Ge, D.; Zhao, B.X.; Liu, Y.R.; Lv, H.S.; Ding, J.; Miao, J.Y. Synthesis of novel oxime-containing pyrazole derivatives and discovery of regulators for apoptosis and autophagy in A549 lung cancer cells. Bioorg. Med. Chem. Lett.,  2010, 20(16), 4766-4770.
[http://dx.doi.org/10.1016/j.bmcl.2010.06.121] [PMID: 20637610] 
[66] 
Banday, A.H.; Mir, B.P.; Lone, I.H.; Suri, K.A.; Kumar, H.M.S. Studies on novel D-ring substituted steroidal pyrazolines as potential anticancer agents. Steroids,  2010, 75(12), 805-809.
[http://dx.doi.org/10.1016/j.steroids.2010.02.014] [PMID: 20206644] 
[67] 
Chou, L.C.; Huang, L.J.; Hsu, M.H.; Fang, M.C.; Yang, J.S.; Zhuang, S.H.; Lin, H.Y.; Lee, F.Y.; Teng, C.M.; Kuo, S.C. Synthesis of 1-benzyl-3-(5-hydroxymethyl-2-furyl)selenolo[3,2-c]pyrazole derivatives as new anticancer agents. Eur. J. Med. Chem.,  2010, 45(4), 1395-1402.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.039] [PMID: 20097456] 
[68] 
Rocha, F.V.; Barra, C.V.; Netto, A.V.G.; Mauro, A.E.; Carlos, I.Z.; Frem, R.C.G.; Ananias, S.R.; Quilles, M.B.; Stevanato, A.; da Rocha, M.C. 3,5-Dimethyl-1-thiocarbamoylpyrazole and its Pd(II) complexes: synthesis, spectral studies and antitumor activity. Eur. J. Med. Chem.,  2010, 45(5), 1698-1702.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.073] [PMID: 20116142] 
[69] 
Fan, C.; Su, H.; Zhao, J.; Zhao, B.; Zhang, S.; Miao, J. A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin β4 in H322 lung carcinoma cells. Eur. J. Med. Chem.,  2010, 45(4), 1438-1446.
[http://dx.doi.org/10.1016/j.ejmech.2009.12.048] [PMID: 20089331] 
[70] 
Zheng, L.W.; Zhu, J.; Zhao, B.X.; Huang, Y.H.; Ding, J.; Miao, J.Y. Synthesis, crystal structure and biological evaluation of novel 2-(5-(hydroxymethyl)-3-phenyl-1H-pyrazol-1-yl)-1-phenylethanol derivatives. Eur. J. Med. Chem.,  2010, 45(12), 5792-5799.
[http://dx.doi.org/10.1016/j.ejmech.2010.09.041] [PMID: 20947221] 
[71] 
Xie, Y.S.; Zhao, H.L.; Su, H.; Zhao, B.X.; Liu, J.T.; Li, J.K.; Lv, H.S.; Wang, B.S.; Shin, D.S.; Miao, J.Y. Synthesis, single-crystal characterization and preliminary biological evaluation of novel ferrocenyl pyrazolo[1,5-a]pyrazin-4(5H)-one derivatives. Eur. J. Med. Chem.,  2010, 45(1), 210-218.
[http://dx.doi.org/10.1016/j.ejmech.2009.09.046] [PMID: 19879668] 
[72] 
Nagarapu, L.; Gaikwad, H.K.; Sarikonda, K.; Mateti, J.; Bantu, R.; Raghu, P.S.; Manda, K.M.; Kalvendi, S.V. Synthesis and cytotoxicity evaluation of 1-[3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]-3-aryl-1H-pyrazole-5-carboxylic acid derivatives. Eur. J. Med. Chem.,  2010, 45(11), 4720-4725.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.004] [PMID: 20817327] 
[73] 
Riyadh, S.M.; Farghaly, T.A.; Abdallah, M.A.; Abdalla, M.M.; Abd El-Aziz, M.R. New pyrazoles incorporating pyrazolylpyrazole moiety: synthesis, anti-HCV and antitumor activity. Eur. J. Med. Chem.,  2010, 45(3), 1042-1050.
[http://dx.doi.org/10.1016/j.ejmech.2009.11.050] [PMID: 20022411] 
[74] 
Nitulescu, G.M.; Draghici, C.; Missir, A.V. Synthesis of new pyrazole derivatives and their anticancer evaluation. Eur. J. Med. Chem.,  2010, 45(11), 4914-4919.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.064] [PMID: 20728965] 
[75] 
Hassan, G.S.; Kadry, H.H.; Abou-Seri, S.M.; Ali, M.M.; Mahmoud, A.E. Synthesis and in vitro cytotoxic activity of novel pyrazolo[3,4-d]pyrimidines and related pyrazole hydrazones toward breast adenocarcinoma MCF-7 cell line. Bioorg. Med. Chem.,  2011, 19(22), 6808-6817.
[http://dx.doi.org/10.1016/j.bmc.2011.09.036] [PMID: 22000322] 
[76] 
Lv, P.C.; Li, D.D.; Li, Q.S.; Lu, X.; Xiao, Z.P.; Zhu, H.L. Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents. Bioorg. Med. Chem. Lett.,  2011, 21(18), 5374-5377.
[http://dx.doi.org/10.1016/j.bmcl.2011.07.010] [PMID: 21802290] 
[77] 
Insuasty, B.; Garcia, A.; Quiroga, J.; Abonia, R.; Ortiz, A.; Nogueras, M.; Cobo, J. Efficient microwave-assisted synthesis and antitumor activity of novel 4,4ˈ-methylene bis. [2-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl) phenols]. Eur. J. Med. Chem.,  2011, 46, 2436-2440.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.028] [PMID: 21481989] 
[78] 
Zhang, D.; Wang, G.; Zhao, G.; Xu, W.; Huo, L. Synthesis and cytotoxic activity of novel 3-(1H-indol-3-yl)-1H-pyrazole-5-carbohydrazide derivatives. Eur. J. Med. Chem.,  2011, 46(12), 5868-5877.
[http://dx.doi.org/10.1016/j.ejmech.2011.09.049] [PMID: 22000925] 
[79] 
Rashad, A.E.; Mahmoud, A.E.; Ali, M.M. Synthesis and anticancer effects of some novel pyrazolo[3,4-d]pyrimidine derivatives by generating reactive oxygen species in human breast adenocarcinoma cells. Eur. J. Med. Chem.,  2011, 46(4), 1019-1026.
[http://dx.doi.org/10.1016/j.ejmech.2011.01.013] [PMID: 21315495] 
[80] 
Sobiesiak, M.; Lorenz, I.P.; Mayer, P.; Woźniczka, M.; Kufelnicki, A.; Krajewska, U.; Rozalski, M.; Budzisz, E. Synthesis, X-ray structure and cytotoxic effect of nickel(II) complexes with pyrazole ligands. Eur. J. Med. Chem.,  2011, 46(12), 5917-5926.
[http://dx.doi.org/10.1016/j.ejmech.2011.10.001] [PMID: 22047642] 
[81] 
Liu, N.; Zhang, J.H.; Zhao, B.X.; Zhao, J.; Su, L.; Dong, W.L.; Zhang, S.L.; Miao, J.Y. Microwave-assisted synthesis, crystal structure of pyrazolo[1,5-a]pyrazin-4(5H)-ones and their selective effects on lung cancer cells. Eur. J. Med. Chem.,  2011, 46(6), 2359-2367.
[http://dx.doi.org/10.1016/j.ejmech.2011.03.018] [PMID: 21463913] 
[82] 
Neelarapu, R.; Holzle, D.L.; Velaparthi, S.; Bai, H.; Brunsteiner, M.; Blond, S.Y.; Petukhov, P.A. Design, synthesis, docking, and biological evaluation of novel diazide-containing isoxazole- and pyrazole-based histone deacetylase probes. J. Med. Chem.,  2011, 54(13), 4350-4364.
[http://dx.doi.org/10.1021/jm2001025] [PMID: 21548582] 
[83] 
Abu Thaher, B.; Arnsmann, M.; Totzke, F.; Ehlert, J.E.; Kubbutat, M.H.G.; Schächtele, C.; Zimmermann, M.O.; Koch, P.; Boeckler, F.M.; Laufer, S.A. Tri- and tetrasubstituted pyrazole derivates: regioisomerism switches activity from p38MAP kinase to important cancer kinases. J. Med. Chem.,  2012, 55(2), 961-965.
[http://dx.doi.org/10.1021/jm201391u] [PMID: 22185282] 
[84] 
Liu, J.J.; Zhang, H.; Sun, J.; Wang, Z.C.; Yang, Y.S.; Li, D.D.; Zhang, F.; Gong, H.B.; Zhu, H.L. Synthesis, biological evaluation of novel 4,5-dihydro-2H-pyrazole 2-hydroxyphenyl derivatives as BRAF inhibitors. Bioorg. Med. Chem.,  2012, 20(20), 6089-6096.
[http://dx.doi.org/10.1016/j.bmc.2012.08.020] [PMID: 22985957] 
[85] 
Bai, X.G.; Yu, D.K.; Wang, J.X.; Zhang, H.; He, H.W.; Shao, R.G.; Li, X.M.; Wang, Y.C. Design, synthesis and anticancer activity of 1-acyl-3-amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives. Bioorg. Med. Chem. Lett.,  2012, 22(22), 6947-6951.
[http://dx.doi.org/10.1016/j.bmcl.2012.08.117] [PMID: 23036956] 
[86] 
Baciu-Atudosie, L.; Ghinet, A.; Farce, A.; Dubois, J.; Belei, D.; Bîcu, E. Synthesis and biological evaluation of new phenothiazine derivatives bearing a pyrazole unit as protein farnesyltransferase inhibitors. Bioorg. Med. Chem. Lett.,  2012, 22(22), 6896-6902.
[http://dx.doi.org/10.1016/j.bmcl.2012.09.030] [PMID: 23036952] 
[87] 
Yang, Y.S.; Li, Q.S.; Sun, S.; Zhang, Y.B.; Wang, X.L.; Zhang, F.; Tang, J.F.; Zhu, H.L. Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase. Bioorg. Med. Chem.,  2012, 20(20), 6048-6058.
[http://dx.doi.org/10.1016/j.bmc.2012.08.043] [PMID: 22985962] 
[88] 
Qiu, K.M.; Wang, H.H.; Wang, L.M.; Luo, Y.; Yang, X.H.; Wang, X.M.; Zhu, H.L. Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors. Bioorg. Med. Chem.,  2012, 20(6), 2010-2018.
[http://dx.doi.org/10.1016/j.bmc.2012.01.051] [PMID: 22361272] 
[89] 
Mulakayala, N.; Kandagatla, B. Ismail; Rapolu, R.K.; Rao, P.; Mulakayala, C.; Kumar, C.S.; Iqbal, J.; Oruganti, S. InCl3-Catalysed synthesis of 2-aryl quinazolin-4(3H)-ones and 5-aryl pyrazolo[4,3-d] pyrimidine-7(6H)-ones and their evaluation as potential anticancer agents. Bioorg. Med. Chem. Lett.,  2012, 22, 5063-5066.
[http://dx.doi.org/10.1016/j.bmcl.2012.06.003] [PMID: 22749421] 
[90] 
Li, X.; Lu, X.; Xing, M.; Yang, X.H.; Zhao, T.T.; Gong, H.B.; Zhu, H.L. Synthesis, biological evaluation, and molecular docking studies of N,1,3-triphenyl-1H-pyrazole-4-carboxamide derivatives as anticancer agents. Bioorg. Med. Chem. Lett.,  2012, 22(11), 3589-3593.
[http://dx.doi.org/10.1016/j.bmcl.2012.04.066] [PMID: 22572580] 
[91] 
Lv, H.S.; Kong, X.Q.; Ming, Q.Q.; Jin, X.; Miao, J.Y.; Zhao, B.X. Synthesis of 5-benzyl-2-phenylpyrazolo[1,5-a]pyrazin-4,6(5H,7H)-dione derivatives and discovery of an apoptosis inducer for H322 lung cancer cells. Bioorg. Med. Chem. Lett.,  2012, 22(2), 844-849.
[http://dx.doi.org/10.1016/j.bmcl.2011.12.049] [PMID: 22209459] 
[92] 
Huang, X.F.; Lu, X.; Zhang, Y.; Song, G.Q.; He, Q.L.; Li, Q.S.; Yang, X.H.; Wei, Y.; Zhu, H.L. Synthesis, biological evaluation, and molecular docking studies of N-((1,3-diphenyl-1H-pyrazol-4-yl)methyl)aniline derivatives as novel anticancer agents. Bioorg. Med. Chem.,  2012, 20(16), 4895-4900.
[http://dx.doi.org/10.1016/j.bmc.2012.06.056] [PMID: 22819191] 
[93] 
Li, X.; Liu, J.L.; Yang, X.H.; Lu, X.; Zhao, T.T.; Gong, H.B.; Zhu, H.L. Synthesis, biological evaluation and molecular docking studies of 3-(1,3-diphenyl-1H-pyrazol-4-yl)-N-phenylacrylamide derivatives as inhibitors of HDAC activity. Bioorg. Med. Chem.,  2012, 20(14), 4430-4436.
[http://dx.doi.org/10.1016/j.bmc.2012.05.031] [PMID: 22705022] 
[94] 
Li, C.Y.; Li, Q.S.; Yan, L.; Sun, X.G.; Wei, R.; Gong, H.B.; Zhu, H.L. Synthesis, biological evaluation and 3D-QSAR studies of novel 4,5-dihydro-1H-pyrazole niacinamide derivatives as BRAF inhibitors. Bioorg. Med. Chem.,  2012, 20(12), 3746-3755.
[http://dx.doi.org/10.1016/j.bmc.2012.04.047] [PMID: 22583669] 
[95] 
Huang, X.F.; Tang, J.F.; Ji, J.L.; Wang, X.L.; Ruan, B.F. Synthesis, characterization and anti-tumor activity of novel amide derivatives containing ferrocenyl pyrazole-moiety. J. Organomet. Chem.,  2012, 706–707, 113-123.
[http://dx.doi.org/10.1016/j.jorganchem.2012.02.001] 
[96] 
Abd El Hamid, M.K.; Mihovilovic, M.D.; El-Nassan, H.B. Synthesis of novel pyrazolo[3,4-d]pyrimidine derivatives as potential anti-breast cancer agents. Eur. J. Med. Chem.,  2012, 57, 323-328.
[http://dx.doi.org/10.1016/j.ejmech.2012.09.031] [PMID: 23085106] 
[97] 
Metwally, M.A.; Gouda, M.A.; Harmal, A.N.; Khalil, A.M. Synthesis, antitumor, cytotoxic and antioxidant evaluation of some new pyrazolotriazines attached to antipyrine moiety. Eur. J. Med. Chem.,  2012, 56, 254-262.
[http://dx.doi.org/10.1016/j.ejmech.2012.08.034] [PMID: 23022735] 
[98] 
Shen, S.L.; Zhu, J.; Li, M.; Zhao, B.X.; Miao, J.Y. Synthesis of ferrocenyl pyrazole-containing chiral aminoethanol derivatives and their inhibition against A549 and H322 lung cancer cells. Eur. J. Med. Chem.,  2012, 54, 287-294.
[http://dx.doi.org/10.1016/j.ejmech.2012.05.008] [PMID: 22683243] 
[99] 
Liu, Y.R.; Luo, J.Z.; Duan, P.P.; Shao, J.; Zhao, B.X.; Miao, J.Y. Synthesis of pyrazole peptidomimetics and their inhibition against A549 lung cancer cells. Bioorg. Med. Chem. Lett.,  2012, 22(22), 6882-6887.
[http://dx.doi.org/10.1016/j.bmcl.2012.09.032] [PMID: 23044370] 
[100] 
Abdelgawad, M.A.; Elshemy, H.A.H.; Ahamed, O.M. Synthesis and anticancer activity of substituted pyrazole derivatives. Org. Chem. Ind. J.,  2013, 9(11), 453-462.
[101] 
Baviskar, A.T.; Banerjee, U.C.; Gupta, M.; Singh, R.; Kumar, S.; Gupta, M.K.; Kumar, S.; Raut, S.K.; Khullar, M.; Singh, S.; Kumar, R. Synthesis of imine-pyrazolopyrimidinones and their mechanistic interventions on anticancer activity. Bioorg. Med. Chem.,  2013, 21(18), 5782-5793.
[http://dx.doi.org/10.1016/j.bmc.2013.07.016] [PMID: 23920485] 
[102] 
Zheng, Y.; Zheng, M.; Ling, X.; Liu, Y.; Xue, Y.; An, L.; Gu, N.; Ji, M. Design, synthesis, quantum chemical studies and biological activity evaluation of pyrazole-benzimidazole derivatives as potent Aurora A/B kinase inhibitors. Bioorg. Med. Chem. Lett.,  2013, 23(12), 3523-3530.
[http://dx.doi.org/10.1016/j.bmcl.2013.04.039] [PMID: 23664099] 
[103] 
Koca, İ.; Özgür, A.; Coşkun, K.A.; Tutar, Y. Synthesis and anticancer activity of acyl thioureas bearing pyrazole moiety. Bioorg. Med. Chem.,  2013, 21(13), 3859-3865.
[http://dx.doi.org/10.1016/j.bmc.2013.04.021] [PMID: 23664495] 
[104] 
Suchaud, V.; Gavara, L.; Saugues, E.; Nauton, L.; Théry, V.; Anizon, F.; Moreau, P. Identification of 1,6-dihydropyrazolo[4,3-c]carbazoles and 3,6-dihydropyrazolo[3,4-c]carbazoles as new Pim kinase inhibitors. Bioorg. Med. Chem.,  2013, 21(14), 4102-4111.
[http://dx.doi.org/10.1016/j.bmc.2013.05.011] [PMID: 23735828] 
[105] 
Toton, E.; Ignatowicz, E.; Bernard, M.K.; Kujawski, J.; Rybczynska, M. Evaluation of apoptotic activity of new condensed pyrazole derivatives. J. Physiol. Pharmacol.,  2013, 64(1), 115-123.
[PMID: 23568979] 
[106] 
Rao, V.K.; Tiwari, R.; Chhikara, B.S.; Shirazi, A.N.; Parang, K.; Kumar, A. Copper triflate-mediated synthesis of 1,3,5-triarylpyrazoles in [bmim][PF6] ionic liquid and evaluation of their anticancer activities. RSC Advances,  2013, 3(35), 15396-15403.
[http://dx.doi.org/10.1039/c3ra41830h] [PMID: 24163734] 
[107] 
Zhu, S.L.; Wu, Y.; Liu, C.J.; Wei, C.Y.; Tao, J.C.; Liu, H.M. Synthesis and in vitro cytotoxic activity evaluation of novel heterocycle bridged carbothioamide type isosteviol derivatives as antitumor agents. Bioorg. Med. Chem. Lett.,  2013, 23(5), 1343-1346.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.091] [PMID: 23347685] 
[108] 
Huang, X.F.; Wang, L.Z.; Tang, L.; Lu, Y.X.; Wang, F.; Song, G.Q.; Ruan, B.F. Synthesis, characterization and antitumor activity of novel ferrocene derivatives containing pyrazolyl-moiety. J. Organomet. Chem.,  2013, 887, 71-79.
[109] 
Kamal, A.; Shaik, A.B.; Jain, N.; Kishor, C.; Nagabhushana, A.; Supriya, B.; Kumar, G.B.; Chourasiya, S.S.; Suresh, Y.; Mishra, R.K.; Addlagatta, A. Design and Synthesis of Pyrazole - Oxindole Conjugates Targeting Tubulin Polymerization as New Anticancer Agents. Eur. J. Med. Chem.,  2013, 19, 948-959.
[PMID: 25599948] 
[110] 
Srivastava, N.; Kumar, N.; Yadav, M.; Pathak, D. Synthesis of pyrazole derivatives: a new therapeutic approach for antiubercular and anticancer activity. J. Pharm. Res.,  2013, 12, 5-14.
[http://dx.doi.org/10.18579/jpcrkc/2013/12/1/79117] 
[111] 
Luo, Y.; Zhang, S.; Qiu, K.M.; Liu, Z.J.; Yang, Y.S.; Fu, J.; Zhong, W.Q.; Zhu, H.L. Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors. Bioorg. Med. Chem. Lett.,  2013, 23(4), 1091-1095.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.010] [PMID: 23312949] 
[112] 
El-Gamal, M.I.; Park, Y.S.; Chi, D.Y.; Yoo, K.H.; Oh, C.H. New triarylpyrazoles as broad-spectrum anticancer agents: design, synthesis, and biological evaluation. Eur. J. Med. Chem.,  2013, 65, 315-322.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.067] [PMID: 23732996] 
[113] 
Kumar, J.A.; Saidachary, G.; Mallesham, G.; Sridhar, B.; Jain, N.; Kalivendi, S.V.; Rao, V.J.; Raju, B.C. Synthesis, anticancer activity and photophysical properties of novel substituted 2-oxo-2H-chromenylpyrazolecarboxylates. Eur. J. Med. Chem.,  2013, 65, 389-402.
[http://dx.doi.org/10.1016/j.ejmech.2013.03.042] [PMID: 23748152] 
[114] 
El-Borai, M.A.; Rizk, H.F.; Beltagy, D.M.; El-Deeb, I.Y. Microwave-assisted synthesis of some new pyrazolopyridines and their antioxidant, antitumor and antimicrobial activities. Eur. J. Med. Chem.,  2013, 66, 415-422.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.043] [PMID: 23831694] 
[115] 
Dong, J.J.; Li, Q.S.; Wang, S.F.; Li, C.Y.; Zhao, X.; Qiu, H.Y.; Zhao, M.Y.; Zhu, H.L. Synthesis, biological evaluation and molecular docking of novel 5-phenyl-1H-pyrazol derivatives as potential BRAF(V600E) inhibitors. Org. Biomol. Chem.,  2013, 11(37), 6328-6337.
[http://dx.doi.org/10.1039/c3ob40776d] [PMID: 23942809] 
[116] 
Du, K.; Xia, C.; Wei, M.; Chen, X.; Zhang, P. Microwave-assisted rapid synthesis of sugar-based pyrazole derivatives with anticancer activity in water. RSC,  2013, 00, 1-3.
[117] 
Palanisamy, P.; Kumaresan, S. Analogues of N,1-diphenyl-4,5-dihydro-1H[1]benzothiepino[5,4-c]pyrazole-3-carboxamide and N,1-diphenyl-4,5-dihydro-1H-[1]benzothiepino[5,4-c]pyrazole-3-carboxamide-6,6-dioxide: syntheses, characterization, antimicrobial, antituberculosis, and antitumor activity. RSC,  2013, 3, 4704-4716.
[http://dx.doi.org/10.1039/c3ra23124k] 
[118] 
Minegishi, H.; Fukashiro, S.; Ban, H.S.; Nakamura, H. Discovery of Indenopyrazoles as a New Class of Hypoxia Inducible Factor (HIF)-1 Inhibitors. ACS Med. Chem. Lett.,  2013, 4(2), 297-301.
[http://dx.doi.org/10.1021/ml3004632] [PMID: 24900662] 
[119] 
Mojzych, M.; Dolashki, A.; Voelter, W. Synthesis of pyrazolo[4,3-e][1,2,4]triazine sulfonamides, novel Sildenafil analogs with tyrosinase inhibitory activity. Bioorg. Med. Chem.,  2014, 22(23), 6616-6624.
[http://dx.doi.org/10.1016/j.bmc.2014.10.009] [PMID: 25456386] 
[120] 
Li, S.; Xu, S.; Tang, Y.; Ding, S.; Zhang, J.; Wang, S.; Zhou, G.; Zhou, C.; Li, X. Synthesis, anticancer activity and DNA-binding properties of novel 4-pyrazolyl-1,8-naphthalimide derivatives. Bioorg. Med. Chem. Lett.,  2014, 24(2), 586-590.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.014] [PMID: 24370011] 
[121] 
Kurumurthy, C.; Veeraswamy, B.; Sambasiva Rao, P.; Santhosh Kumar, G.; Shanthan Rao, P.; Loka Reddy, V.; Venkateswara Rao, J.; Narsaiah, B. Synthesis of novel 1,2,3-triazole tagged pyrazolo[3,4-b]pyridine derivatives and their cytotoxic activity. Bioorg. Med. Chem. Lett.,  2014, 24(3), 746-749.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.107] [PMID: 24424132] 
[122] 
Yuan, J.W.; Wang, S.F.; Luo, Z.L.; Qiu, H.Y.; Wang, P.F.; Zhang, X.; Yang, Y.A.; Yin, Y.; Zhang, F.; Zhu, H.L. Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents. Bioorg. Med. Chem. Lett.,  2014, 24(10), 2324-2328.
[http://dx.doi.org/10.1016/j.bmcl.2014.03.072] [PMID: 24731281] 
[123] 
Nakao, S.; Mabuchi, M.; Shimizu, T.; Itoh, Y.; Takeuchi, Y.; Ueda, M.; Mizuno, H.; Shigi, N.; Ohshio, I.; Jinguji, K.; Ueda, Y.; Yamamoto, M.; Furukawa, T.; Aoki, S.; Tsujikawa, K.; Tanaka, A. Design and synthesis of prostate cancer antigen-1 (PCA-1/ALKBH3) inhibitors as anti-prostate cancer drugs. Bioorg. Med. Chem. Lett.,  2014, 24(4), 1071-1074.
[http://dx.doi.org/10.1016/j.bmcl.2014.01.008] [PMID: 24461353] 
[124] 
Wang, S.F.; Zhu, Y.L.; Zhu, P.T.; Makawana, J.A.; Zhang, Y.L.; Zhao, M.Y.; Lv, P.C.; Zhu, H.L. Design, synthesis and biological evaluation of novel 5-phenyl-1H-pyrazole derivatives as potential BRAF(V600E) inhibitors. Bioorg. Med. Chem.,  2014, 22(21), 6201-6208.
[http://dx.doi.org/10.1016/j.bmc.2014.08.029] [PMID: 25267006] 
[125] 
Raghav, N.; Garg, S. N-formylpyrazolines and N-benzoylpyrazolines as novel inhibitors of mammalian cathepsin B and cathepsin H. Bioorg. Chem.,  2014, 57, 43-50.
[http://dx.doi.org/10.1016/j.bioorg.2014.07.012] [PMID: 25181676] 
[126] 
Xu, Y.; Liu, X.H.; Saunders, M.; Pearce, S.; Foulks, J.M.; Parnell, K.M.; Clifford, A.; Nix, R.N.; Bullough, J.; Hendrickson, T.F.; Wright, K.; McCullar, M.V.; Kanner, S.B.; Ho, K.K. Discovery of 3-(trifluoromethyl)-1H-pyrazole-5-carboxamide activators of the M2 isoform of pyruvate kinase (PKM2). Bioorg. Med. Chem. Lett.,  2014, 24(2), 515-519.
[http://dx.doi.org/10.1016/j.bmcl.2013.12.028] [PMID: 24374270] 
[127] 
Zhao, M.Y.; Yin, Y.; Yu, X.W.; Sangani, C.B.; Wang, S.F.; Lu, A.M.; Yang, L.F.; Lv, P.C.; Jiang, M.G.; Zhu, H.L. Synthesis, biological evaluation and 3D-QSAR study of novel 4,5-dihydro-1H-pyrazole thiazole derivatives as BRAF(V600E) inhibitors. Bioorg. Med. Chem.,  2015, 23(1), 46-54.
[http://dx.doi.org/10.1016/j.bmc.2014.11.029] [PMID: 25496804] 
[128] 
Uremaru, N.; Chang, E.C.; Yen, W.P.; Yeh, M.Y.; Juang, S.H.; Wang, F.F. Synthesis and evaluation of in vitro bioactivity for polysubstituted N-arylpyrazole derivatives. Arab. J. Chem.,  2014, 12, 1908-1917.
[http://dx.doi.org/10.1016/j.arabjc.2014.12.004] 
[129] 
Hopa, C.; Yildirim, H.; Kara, H.; Kurtaran, R.; Alkan, M. Synthesis, characterization and anti-proliferative activity of Cd(II) complexes with NNN type pyrazole-based ligand and pseudohalide ligands as coligand. Spectrochim. Acta A Mol. Biomol. Spectrosc.,  2014, 121, 282-287.
[http://dx.doi.org/10.1016/j.saa.2013.10.028] [PMID: 24252293] 
[130] 
Grazul, M.; Besic-Gyenge, E.; Maake, C.; Ciolkowski, M.; Czyz, M.; Sigel, R.K.O.; Budzisz, E. Synthesis, physico-chemical properties and biological analysis of newly obtained copper(II) complexes with pyrazole derivatives. J. Inorg. Biochem.,  2014, 135, 68-76.
[http://dx.doi.org/10.1016/j.jinorgbio.2014.02.014] [PMID: 24662465] 
[131] 
Banday, A.H.; Shameem, S.A.; Jeelani, S. Steroidal pyrazolines and pyrazoles as potential 5α-reductase inhibitors: synthesis and biological evaluation. Steroids,  2014, 92, 13-19.
[http://dx.doi.org/10.1016/j.steroids.2014.09.004] [PMID: 25278254] 
[132] 
Shi, J.B.; Tang, W.J.; Qi, X.B.; Li, R.; Liu, X.H.; Liu, X.H. Novel pyrazole-5-carboxamide and pyrazole-pyrimidine derivatives: synthesis and anticancer activity. Eur. J. Med. Chem.,  2015, 90, 889-896.
[http://dx.doi.org/10.1016/j.ejmech.2014.12.013] [PMID: 25554922] 
[133] 
Cankara Pirol, Ş.; Çalışkan, B.; Durmaz, I.; Atalay, R.; Banoglu, E. Synthesis and preliminary mechanistic evaluation of 5-(p-tolyl)-1-(quinolin-2-yl)pyrazole-3-carboxylic acid amides with potent antiproliferative activity on human cancer cell lines. Eur. J. Med. Chem.,  2014, 87, 140-149.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.056] [PMID: 25247770] 
[134] 
Orlikova, B.; Chaouni, W.; Schumacher, M.; Aadil, M.; Diederich, M.; Kirsch, G. Synthesis and bioactivity of novel amino-pyrazolopyridines. Eur. J. Med. Chem.,  2014, 85, 450-457.
[http://dx.doi.org/10.1016/j.ejmech.2014.08.008] [PMID: 25108361] 
[135] 
Zhang, J.F.; Li, M.; Miao, J.Y.; Zhao, B.X. Biological activities of novel pyrazolyl hydroxamic acid derivatives against human lung cancer cell line A549. Eur. J. Med. Chem.,  2014, 83, 516-525.
[http://dx.doi.org/10.1016/j.ejmech.2014.06.065] [PMID: 24996138] 
[136] 
Kumar, V.; Kaur, K.; Karelia, D.N.; Beniwal, V.; Gupta, G.K.; Sharma, A.K.; Gupta, A.K. Synthesis and biological evaluation of some 2-(3,5-dimethyl-1H-pyrazol-1-yl)-1-arylethanones: antibacterial, DNA photocleavage, and anticancer activities. Eur. J. Med. Chem.,  2014, 81, 267-276.
[http://dx.doi.org/10.1016/j.ejmech.2014.05.004] [PMID: 24849271] 
[137] 
Grosse, S.; Mathieu, V.; Pillard, C.; Massip, S.; Marchivie, M.; Jarry, C.; Bernard, P.; Kiss, R.; Guillaumet, G. New imidazo[1,2-b]pyrazoles as anticancer agents: synthesis, biological evaluation and structure activity relationship analysis. Eur. J. Med. Chem.,  2014, 84, 718-730.
[http://dx.doi.org/10.1016/j.ejmech.2014.07.057] [PMID: 25064349] 
[138] 
Yao, Y.; Liao, C.; Li, Z.; Wang, Z.; Sun, Q.; Liu, C.; Yang, Y.; Tu, Z.; Jiang, S. Design, synthesis, and biological evaluation of 1, 3-disubstituted-pyrazole derivatives as new class I and IIb histone deacetylase inhibitors. Eur. J. Med. Chem.,  2014, 86, 639-652.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.024] [PMID: 25218912] 
[139] 
Khloya, P.; Celik, G. SitaRam; Vullo, D.; Supuran, C.T.; Sharma, P.K. 4-Functionalized 1,3-diarylpyrazoles bearing benzenesulfonamide moiety as selective potent inhibitors of the tumor associated carbonic anhydrase isoforms IX and XII. Eur. J. Med. Chem.,  2014, 76, 284-290.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.023] [PMID: 24589484] 
[140] 
Revanna, C.N. Basappa; Srinivasa, V.; Li, F.; Siveen, K.S.; Dai, X.Y.; Swamy, S.N.; Bhadregowda, D.G.; Sethi, G.; Mantelingu, K.; Bender, A.; Rangappa, K.S.; Synthesis and biological evaluation of tetrahydropyridine pyrazoles as inhibitors of STAT3 phosphorylation. RSC,  2014, 5, 32-40.
[141] 
Zhang, W.M.; Xing, M.; Zhao, T.T.; Ren, Y.J.; Yang, X.H.; Yang, Y.S.; Lv, P.C.; Zhu, H.L. Synthesis, molecular modeling and biological evaluation of cinnamic acid derivatives with pyrazole moieties as novel anticancer agents. RSC,  2014, 4, 37197-37207.
[http://dx.doi.org/10.1039/C4RA05257A] 
[142] 
Luo, Y.; Zhou, Y.; Fu, J.; Zhu, H.L. 4,5-Dihydropyrazole derivatives containing oxygen bearing heterocycles as potential telomerase inhibitors with anticancer activity. RSC,  2014, 4, 23904-23913.
[http://dx.doi.org/10.1039/c4ra02200a] 
[143] 
Qin, Y.J.; Xing, M.; Zhang, Y.L.; Makawana, J.A.; Jiang, A.Q.; Zhu, H.L. Design, synthesis and biological evaluation of (1,3-diphenyl-1H-pyrazol-4-yl)methyl benzoate derivatives as potential BRAFV600E inhibitors. RSC,  2014, 4, 52702-52711.
[http://dx.doi.org/10.1039/C4RA08708A] 
[144] 
Abd El-Karim, S.S.; Anwar, M.M.; Mohamed, N.A.; Nasr, T.; Elseginy, S.A. Design, synthesis, biological evaluation and molecular docking studies of novel benzofuran-pyrazole derivatives as anticancer agents. Bioorg. Chem.,  2015, 63, 1-12.
[http://dx.doi.org/10.1016/j.bioorg.2015.08.006] [PMID: 26368040] 
[145] 
Kamal, A.; Shaik, A.B.; Polepalli, S.; Kumar, G.B.; Reddy, V.S.; Mahesh, R.; Garimella, S.; Jain, N. Synthesis of arylpyrazole linked benzimidazole conjugates as potential microtubule disruptors. Bioorg. Med. Chem.,  2015, 23(5), 1082-1095.
[http://dx.doi.org/10.1016/j.bmc.2015.01.004] [PMID: 25648686] 
[146] 
Khloya, P.; Ceruso, M.; Ram, S.; Supuran, C.T.; Sharma, P.K. Sulfonamide bearing pyrazolylpyrazolines as potent inhibitors of carbonic anhydrase isoforms 1, 2, 9, 12. Bioorg. Med. Lett,  2015, 25, 3208-3212.
[http://dx.doi.org/10.1016/j.bmcl.2015.05.096] [PMID: 26105196] 
[147] 
Yasuda, Y.; Arakawa, T.; Nawata, Y.; Shimada, S.; Oishi, S.; Fujii, N.; Nishimura, S.; Hattori, A.; Kakeya, H. Design, synthesis, and structure-activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors. Bioorg. Med. Chem.,  2015, 23(8), 1776-1787.
[http://dx.doi.org/10.1016/j.bmc.2015.02.038] [PMID: 25773014] 
[148] 
Mojzych, M.; Ceruso, M.; Bielawska, A.; Bielawski, K.; Fornal, E.; Supuran, C.T. New pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors. Bioorg. Med. Chem.,  2015, 23(13), 3674-3680.
[http://dx.doi.org/10.1016/j.bmc.2015.04.011] [PMID: 25921266] 
[149] 
Chen, Z.; Wang, Z.C.; Yan, X.Q.; Wang, P.F.; Lu, X.Y.; Chen, L.W.; Zhu, H.L.; Zhang, H.W. Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors. Bioorg. Med. Chem. Lett.,  2015, 25(9), 1947-1951.
[http://dx.doi.org/10.1016/j.bmcl.2015.03.022] [PMID: 25866240] 
[150] 
Bavetsias, V.; Pérez-Fuertes, Y.; McIntyre, P.J.; Atrash, B.; Kosmopoulou, M.; O’Fee, L.; Burke, R.; Sun, C.; Faisal, A.; Bush, K.; Avery, S.; Henley, A.; Raynaud, F.I.; Linardopoulos, S.; Bayliss, R.; Blagg, J. 7-(Pyrazol-4-yl)-3H-imidazo[4,5-b]pyridine-based derivatives for kinase inhibition: Co-crystallisation studies with Aurora-A reveal distinct differences in the orientation of the pyrazole N1-substituent. Bioorg. Med. Chem. Lett.,  2015, 25(19), 4203-4209.
[http://dx.doi.org/10.1016/j.bmcl.2015.08.003] [PMID: 26296477] 
[151] 
Yan, X.Q.; Wang, Z.C.; Li, Z.; Wang, P.F.; Qiu, H.Y.; Chen, L.W.; Lu, X.Y.; Lv, P.C.; Zhu, H.L. Sulfonamide derivatives containing dihydropyrazole moieties selectively and potently inhibit MMP-2/MMP-9: Design, synthesis, inhibitory activity and 3D-QSAR analysis. Bioorg. Med. Chem. Lett.,  2015, 25(20), 4664-4671.
[http://dx.doi.org/10.1016/j.bmcl.2015.08.026] [PMID: 26346367] 
[152] 
Nitulescu, G.M.; Draghici, C.; Olaru, O.T.; Matei, L.; Ioana, A.; Dragu, L.D.; Bleotu, C. Synthesis and apoptotic activity of new pyrazole derivatives in cancer cell lines. Bioorg. Med. Chem.,  2015, 23(17), 5799-5808.
[http://dx.doi.org/10.1016/j.bmc.2015.07.010] [PMID: 26193760] 
[153] 
Phillipson, L.J.; Segal, D.H.; Nero, T.L.; Parker, M.W.; Wan, S.S.; de Silva, M.; Guthridge, M.A.; Wei, A.H.; Burns, C.J. Discovery and SAR of novel pyrazolo[1,5-a]pyrimidines as inhibitors of CDK9. Bioorg. Med. Chem.,  2015, 23(19), 6280-6296.
[http://dx.doi.org/10.1016/j.bmc.2015.08.035] [PMID: 26349627] 
[154] 
Zhang, H.; Zhu, P.; Liu, J.; Lin, Y.; Yao, H.; Jiang, J.; Ye, W.; Wu, X.; Xu, J. Synthesis, in vitro and in vivo antitumor activity of pyrazole-fused 23-hydroxybetulinic acid derivatives. Bioorg. Med. Chem. Lett.,  2015, 25(3), 728-732.
[http://dx.doi.org/10.1016/j.bmcl.2014.11.058] [PMID: 25529742] 
[155] 
Chen, T.C.; Guh, J.H.; Hsu, H.W.; Chen, C.L.; Lee, C.C.; Wu, C.L.; Lee, Y.R.; Lin, J.J.; Yu, D.S.; Huang, H.S. Synthesis and biological evaluation of anthra[1,9-cd]pyrazol-6(2H)-one scaffold derivatives as potential anticancer agent. Arab. J. Chem.,  2015, 12, 2864-2881.
[http://dx.doi.org/10.1016/j.arabjc.2015.06.017] 
[156] 
Qi, D.Q.; Yu, C.M.; You, J.Z.; Yang, G.H.; Wang, X.J.; Zhang, Y.P. Synthesis, crystal structure, fluorescence and xanthine oxidase inhibitory activity of pyrazole-based 1,3,4-oxadiazole derivatives. J. Mol. Struct.,  2015, 1100, 421-428.
[http://dx.doi.org/10.1016/j.molstruc.2015.07.067] 
[157] 
Qin, Y.J.; Li, Y.J.; Jiang, A.Q.; Yang, M.R.; Zhu, Q.Z.; Dong, H.; Zhu, H.L. Design, synthesis and biological evaluation of novel pyrazoline-containing derivatives as potential tubulin assembling inhibitors. Eur. J. Med. Chem.,  2015, 94, 447-457.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.058] [PMID: 25828827] 
[158] 
Szabó, N.; Iványi, Z.; Szécsi, M.; Julesz, J.; Mernyák, E.; Huber, J.; Wölfling, J.; Minorics, R.; Zupkó, I.; Schneider, G. Synthesis of methoxycarbonylpyrazolylandrostene derivatives, and their potential inhibitory effect on androgen biosynthesis and cell proliferation. Steroids,  2015, 98, 143-152.
[http://dx.doi.org/10.1016/j.steroids.2015.03.008] [PMID: 25804762] 
[159] 
Nitulescu, G.M.; Matei, L.; Aldea, I.M.; Draghici, C.; Olaru, O.T.; Bleotu, C. Ultrasound-assisted synthesis and anticancer evaluation of new pyrazole derivatives as cell cycle inhibitors. Arab. J. Chem.,  2015, 12, 816-824.
[http://dx.doi.org/10.1016/j.arabjc.2015.12.006] 
[160] 
Reddy, T.S.; Kulhari, H.; Reddy, V.G.; Bansal, V.; Kamal, A.; Shukla, R. Design, synthesis and biological evaluation of 1,3-diphenyl-1H-pyrazole derivatives containing benzimidazole skeleton as potential anticancer and apoptosis inducing agents. Eur. J. Med. Chem.,  2015, 101, 790-805.
[http://dx.doi.org/10.1016/j.ejmech.2015.07.031] [PMID: 26231080] 
[161] 
Vaarla, K.; Kesharwani, R.K.; Santosh, K.; Vedula, R.R.; Kotamraju, S.; Toopurani, M.K. Synthesis, biological activity evaluation and molecular docking studies of novel coumarin substituted thiazolyl-3-aryl-pyrazole-4-carbaldehydes. Bioorg. Med. Chem. Lett.,  2015, 25(24), 5797-5803.
[http://dx.doi.org/10.1016/j.bmcl.2015.10.042] [PMID: 26542964] 
[162] 
Hassan, A.S.; Hafez, T.S.; Osman, S.A. Synthesis, Characterization, and Cytotoxicity of Some New 5-Aminopyrazole and Pyrazolo[1,5-a]pyrimidine Derivatives. Sci. Pharm.,  2014, 83(1), 27-39.
[http://dx.doi.org/10.3797/scipharm.1409-14] [PMID: 26839799] 
[163] 
Wang, S.F.; Yin, Y.; Zhang, Y.L.; Mi, S.W.; Zhao, M.Y.; Lv, P.C.; Wang, B.Z.; Zhu, H.L. Synthesis, biological evaluation and 3D-QSAR studies of novel 5-phenyl-1H-pyrazol cinnamamide derivatives as novel antitubulin agents. Eur. J. Med. Chem.,  2015, 93, 291-299.
[http://dx.doi.org/10.1016/j.ejmech.2015.02.018] [PMID: 25703297] 
[164] 
Dinesha; Viveka, S.; Priya, B.K.; Pai, K.S.; 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.
[http://dx.doi.org/10.1016/j.ejmech.2015.09.029] [PMID: 26433616] 
[165] 
Maggio, B.; Raimondi, M.V.; Raffa, D.; Plescia, F.; Cascioferro, S.; Cancemi, G.; Tolomeo, M.; Grimaudo, S.; Daidone, G. Synthesis and antiproliferative activity of 3-(2-chloroethyl)-5-methyl-6-phenyl-8-(trifluoromethyl)-5,6-dihydropyrazolo[3,4-f][1,2,3,5]tetrazepin-4-(3H)-one. Eur. J. Med. Chem.,  2015, 96, 98-104.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.004] [PMID: 25874335] 
[166] 
Li, J.; Zhao, X.; Li, L.; Yuan, Z.; Tan, F.; Shi, B.; Zhang, J. Design, synthesis and cytotoxic activity of a novel series of steroidal phenylpyrazoles. Steroids,  2016, 107, 45-54.
[http://dx.doi.org/10.1016/j.steroids.2015.12.018] [PMID: 26742627] 
[167] 
Srinivasa Reddy, T.; Kulhari, H.; Ganga Reddy, V.; Subba Rao, A.V.; Bansal, V.; Kamal, A.; Shukla, R. Synthesis and biological evaluation of pyrazolo-triazole hybrids as cytotoxic and apoptosis inducing agents. Org. Biomol. Chem.,  2015, 13(40), 10136-10149.
[http://dx.doi.org/10.1039/C5OB00842E] [PMID: 26346902] 
[168] 
Minegishi, H.; Futamura, Y.; Fukashiro, S.; Muroi, M.; Kawatani, M.; Osada, H.; Nakamura, H. Methyl 3-((6-methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)amino)benzoate (GN39482) as a tubulin polymerization inhibitor identified by MorphoBase and ChemProteoBase profiling methods. J. Med. Chem.,  2015, 58(10), 4230-4241.
[http://dx.doi.org/10.1021/acs.jmedchem.5b00035] [PMID: 25938266] 
[169] 
Xu, Y.; Brenning, B.G.; Kultgen, S.G.; Foulks, J.M.; Clifford, A.; Lai, S.; Chan, A.; Merx, S.; McCullar, M.V.; Kanner, S.B.; Ho, K.K. Synthesis and Biological Evaluation of Pyrazolo[1,5-a]pyrimidine Compounds as Potent and Selective Pim-1 Inhibitors. ACS Med. Chem. Lett.,  2014, 6(1), 63-67.
[http://dx.doi.org/10.1021/ml500300c] [PMID: 25589932] 
[170] 
Ahmad, P.; Woo, H.; Jun, K.Y.; Kadi, A.A.; Abdel-Aziz, H.A.; Kwon, Y.; Rahman, A.F.M. Design, synthesis, topoisomerase I & II inhibitory activity, antiproliferative activity, and structure-activity relationship study of pyrazoline derivatives: An ATP-competitive human topoisomerase IIα catalytic inhibitor. Bioorg. Med. Chem.,  2016, 24(8), 1898-1908.
[http://dx.doi.org/10.1016/j.bmc.2016.03.017] [PMID: 26988802] 
[171] 
Ismail, M.F.; Khalifa, N.M.; Fahmy, H.H. EL-Sahrawy, H.M.; Nossier, E.S. Anticancer evaluation of novel 1,3,4-trisubstituted pyrazole candidates bearing different nitrogenous heterocyclic Moieties. Biomed. Res.,  2016, 27, 1087-1093.
[172] 
Minu, M.; Singh, D.; Mahaddalkar, T.; Lopus, M.; Winter, P.; Ayoub, A.T.; Missiaen, K.; Tilli, T.M.; Pasdar, M.; Tuszynski, J. Chemical synthesis, pharmacological evaluation and in silico analysis of new 2,3,3a,4,5,6-hexahydrocyclopenta[c]pyrazole derivatives as potential anti-mitotic agents. Bioorg. Med. Chem. Lett.,  2016, 26(16), 3855-3861.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.025] [PMID: 27449957] 
[173] 
Dai, H.; Ge, S.; Li, G.; Chen, J.; Shi, Y.; Ye, L.; Ling, Y. Synthesis and bioactivities of novel pyrazole oxime derivatives containing a 1,2,3-thiadiazole moiety. Bioorg. Med. Chem. Lett.,  2016, 26(18), 4504-4507.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.068] [PMID: 27503679] 
[174] 
Shin, S.Y.; Ahn, S.; Yoon, H.; Jung, H.; Jung, Y.; Koh, D.; Lee, Y.H.; Lim, Y. Colorectal anticancer activities of polymethoxylated 3-naphthyl-5-phenylpyrazoline-carbothioamides. Bioorg. Med. Chem. Lett.,  2016, 26(17), 4301-4309.
[http://dx.doi.org/10.1016/j.bmcl.2016.07.037] [PMID: 27476140] 
[175] 
Eissa, I.H.; El-Naggar, A.M.; El-Hashash, M.A. Design, synthesis, molecular modeling and biological evaluation of novel 1H-pyrazolo[3,4-b]pyridine derivatives as potential anticancer agents. Bioorg. Chem.,  2016, 67, 43-56.
[http://dx.doi.org/10.1016/j.bioorg.2016.05.006] [PMID: 27253830] 
[176] 
Hafez, H.N.; El-Gazzar, A.B.A.; Al-Hussain, S.A. Novel pyrazole derivatives with oxa/thiadiazolyl, pyrazolyl moieties and pyrazolo[4,3-d]-pyrimidine derivatives as potential antimicrobial and anticancer agents. Bioorg. Med. Chem. Lett.,  2016, 26(10), 2428-2433.
[http://dx.doi.org/10.1016/j.bmcl.2016.03.117] [PMID: 27080187] 
[177] 
Kumar, S.; Ceruso, M.; Tuccinardi, T.; Supuran, C.T.; Sharma, P.K. Pyrazolylbenzo[d]imidazoles as new potent and selective inhibitors of carbonic anhydrase isoforms hCA IX and XII. Bioorg. Med. Chem.,  2016, 24(13), 2907-2913.
[http://dx.doi.org/10.1016/j.bmc.2016.04.061] [PMID: 27166574] 
[178] 
Lamie, P.F. RETRACTED: Design, synthesis, structure-activity relationship and kinase inhibitory activity of substituted 3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4-ones. Bioorg. Med. Chem. Lett.,  2016, 26(13), 3093-3097.
[http://dx.doi.org/10.1016/j.bmcl.2016.05.004] [PMID: 27189674] 
[179] 
LaPorte, M.G.; Wang, Z.; Colombo, R.; Garzan, A.; Peshkov, V.A.; Liang, M.; Johnston, P.A.; Schurdak, M.E.; Sen, M.; Camarco, D.P.; Hua, Y.; Pollock, N.I.; Lazo, J.S.; Grandis, J.R.; Wipf, P.; Huryn, D.M. Optimization of pyrazole-containing 1,2,4-triazolo-[3,4-b]thiadiazines, a new class of STAT3 pathway inhibitors. Bioorg. Med. Chem. Lett.,  2016, 26(15), 3581-3585.
[http://dx.doi.org/10.1016/j.bmcl.2016.06.017] [PMID: 27381083] 
[180] 
Lv, X.H.; Ren, Z.L.; Zhou, B.G.; Li, Q.S.; Chu, M.J.; Liu, D.H.; Mo, K.; Zhang, L.S.; Yao, X.K.; Cao, H.Q. Discovery of N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives as potential antiproliferative agents by inhibiting MEK. Bioorg. Med. Chem.,  2016, 24(19), 4652-4659.
[http://dx.doi.org/10.1016/j.bmc.2016.08.002] [PMID: 27515719] 
[181] 
Shi, W.; Hu, J.; Bao, N.; Li, D.; Chen, L.; Sun, J. Design, synthesis and cytotoxic activities of scopoletin-isoxazole and scopoletin-pyrazole hybrids. Bioorg. Med. Chem. Lett.,  2017, 27(2), 147-151.
[http://dx.doi.org/10.1016/j.bmcl.2016.11.089] [PMID: 27956344] 
[182] 
Tao, X.X.; Duan, Y.T.; Chen, L.W.; Tang, D.J.; Yang, M.R.; Wang, P.F.; Xu, C.; Zhu, H.L. Design, synthesis and biological evaluation of pyrazolyl-nitroimidazole derivatives as potential EGFR/HER-2 kinase inhibitors. Bioorg. Med. Chem. Lett.,  2016, 26(2), 677-683.
[http://dx.doi.org/10.1016/j.bmcl.2015.11.040] [PMID: 26652482] 
[183] 
Yang, Y.S.; Yang, B.; Zou, Y.; Li, G.; Zhu, H.L. Design, biological evaluation and 3D QSAR studies of novel dioxin-containing triaryl pyrazoline derivatives as potential B-Raf inhibitors. Bioorg. Med. Chem.,  2016, 24(13), 3052-3061.
[http://dx.doi.org/10.1016/j.bmc.2016.05.012] [PMID: 27238841] 
[184] 
Rahmouni, A.; Souiei, S.; Belkacem, M.A.; Romdhane, A.; Bouajila, J.; Ben Jannet, H. Synthesis and biological evaluation of novel pyrazolopyrimidines derivatives as anticancer and anti-5-lipoxygenase agents. Bioorg. Chem.,  2016, 66, 160-168.
[http://dx.doi.org/10.1016/j.bioorg.2016.05.001] [PMID: 27179178] 
[185] 
Abdel-latif, E.; Abdel-fattah, S.; Gaffer, H.E.; Etman, H.A. Synthesis and antitumor activity of some new pyrazolo[3,4-d]pyrimidine and pyrazolo[3,4-b]pyridine derivatives. Egypt. j. basic appl. sci,  2016, 3, 118-124.
[186] 
Ismail, M.M.F.; Soliman, D.H.; Farrag, A.M.; Sabour, R. Synthesis, Antitumor activity, Pharmacophore modeling and QSAR studies of novel pyrazoles and pyrazolo [1,5-a] pyrimidines against breast adenocarcinoma mcf-7 cell line. Int. J. Pharm. Pharm. Sci.,  2016, 8, 434-442.
[187] 
Brown, A.W.; Fisher, M.; Tozer, G.M.; Kanthou, C.; Harrity, J.P. Sydnone Cycloaddition Route to Pyrazole-Based Analogs of Combretastatin A4. J. Med. Chem.,  2016, 59(20), 9473-9488.
[http://dx.doi.org/10.1021/acs.jmedchem.6b01128] [PMID: 27690431] 
[188] 
Bonacorso, H.G.; Nogara, P.A.; Silva, F. D’A.; Rosa, W.C.; Wiethan, C.W.; Zanatta, N.; Martins, M.A.P.; Rocha, J.B.T. Convergent synthesis and cytotoxicity of novel trifluoromethyl-substituted (1H-pyrazol-1-yl) (quinolin-4-yl) methanones. J. Fluor. Chem.,  2016, 190, 31-40.
[http://dx.doi.org/10.1016/j.jfluchem.2016.08.012] 
[189] 
Zhou, W.H.; Xu, X.G.; Li, J.; Min, X.; Yao, J.Z.; Dong, G.Q.; Zhuang, C.L.; Miao, Z.Y.; Zhang, W.N. Design, synthesis and structure activity relationship of 4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-ones as potent p53-MDM2 inhibitors. Chin. Chem. Lett.,  2016, 28, 422-425.
[http://dx.doi.org/10.1016/j.cclet.2016.09.001] 
[190] 
Ratkovic, Z.; Muskinja, J.; Burmudzija, A.; Rankovic, B.; Kosanic, M.; Bogdanovi, G.A.; Markovic, B.S.; Nikolic, A.; Arsenijevic, N.; Dordevic, S.; Vukicevic, R.D. Dehydrozingerone based 1-acetyl-5-aryl-4,5-dihydro-1H-pyrazoles: Synthesis, characterization and anticancer activity. J. Mol. Struct.,  2016, 1109, 82-88.
[http://dx.doi.org/10.1016/j.molstruc.2015.12.079] 
[191] 
Wang, F.Q.; Yang, H.; He, B.; Jia, Y.K.; Meng, S.Y.; Zhang, C.; Liu, H.M.; Liu, F.W. A novel domino approach for synthesis of indolyl tetrahydropyrano[4,3-c]pyrazole derivatives as anticancer agents. Tetrahedron,  2016, 72, 5769-5775.
[http://dx.doi.org/10.1016/j.tet.2016.07.078] 
[192] 
Higuera-Padilla, A.R.; Capote, J.; Ortega, D.; Castro, W.; Rodriguez-Cordero, M.; Coll, D.; Hernández-Medina, F.; Fernández-Mestre, M.; Urdanibia, I.; Taylor, P.; Rodriguez, B.; Karam, A. Synthesis, characterization and biological activity of platinum (II) complexes with a tetrapyrazole ligand. Polyhedron,  2016, 102, 321-328.
[http://dx.doi.org/10.1016/j.poly.2015.09.065] 
[193] 
Gamal El-Din, M.M.; El-Gamal, M.I.; Abdel-Maksoud, M.S.; Yoo, K.H.; Oh, C.H. Design, synthesis, broad-spectrum antiproliferative activity, and kinase inhibitory effect of triarylpyrazole derivatives possessing arylamides or arylureas moieties. Eur. J. Med. Chem.,  2016, 119, 122-131.
[http://dx.doi.org/10.1016/j.ejmech.2016.04.048] [PMID: 27155467] 
[194] 
Ganga Reddy, V.; Srinivasa Reddy, T.; Lakshma Nayak, V.; Prasad, B.; Reddy, A.P.; Ravikumar, A.; Taj, S.; Kamal, A. Design, synthesis and biological evaluation of N-((1-benzyl-1H-1,2,3-triazol-4-yl)methyl)-1,3-diphenyl-1H-pyrazole-4-carboxamides as CDK1/Cdc2 inhibitors. Eur. J. Med. Chem.,  2016, 122, 164-177.
[http://dx.doi.org/10.1016/j.ejmech.2016.06.011] [PMID: 27344493] 
[195] 
Mansha, M.; Kumari, U.U.; Cournia, Z.; Ullah, N. Pyrazole-based potent inhibitors of GGT1: Synthesis, biological evaluation, and molecular docking studies. Eur. J. Med. Chem.,  2016, 124, 666-676.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.002] [PMID: 27620969] 
[196] 
Singla, P.; Luxami, V.; Singh, R.; Tandon, V.; Paul, K. Novel pyrazolo[3,4-d]pyrimidine with 4-(1H-benzimidazol-2-yl)-phenylamine as broad spectrum anticancer agents: Synthesis, cell based assay, topoisomerase inhibition, DNA intercalation and bovine serum albumin studies. Eur. J. Med. Chem.,  2017, 126, 24-35.
[http://dx.doi.org/10.1016/j.ejmech.2016.09.093] [PMID: 27744184] 
[197] 
Wang, Y.; Cheng, F.X.; Yuan, X.L.; Tang, W.J.; Shi, J.B.; Liao, C.Z.; Liu, X.H. Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo. Eur. J. Med. Chem.,  2016, 112, 231-251.
[http://dx.doi.org/10.1016/j.ejmech.2016.02.009] [PMID: 26900656] 
[198] 
Kovács, D.; Wölfling, J.; Szabó, N.; Szécsi, M.; Schelz, Z.; Zupkó, I.; Frank, É. Synthesis of novel 17-(4′-formyl)pyrazolylandrosta-5,16-dienes and their derivatives as potent 17α-hydroxylase/C17,20-lyase inhibitors or antiproliferative agents depending on the substitution pattern of the heteroring. Eur. J. Med. Chem.,  2016, 120, 284-295.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.006] [PMID: 27209562] 
[199] 
Ravi, C.; Qayum, A.; Chandra Mohan, D.; Singh, S.K.; Adimurthy, S. Design, synthesis and cytotoxicity studies of novel pyrazolo[1, 5-a]pyridine derivatives. Eur. J. Med. Chem.,  2017, 126, 277-285.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.037] [PMID: 27889631] 
[200] 
Zhan, W.; Xu, L.; Dong, X.; Dong, J.; Yi, X.; Ma, X.; Qiu, N.; Li, J.; Yang, B.; Zhou, Y.; Hu, Y. Design, synthesis and biological evaluation of pyrazol-furan carboxamide analogues as novel Akt kinase inhibitors. Eur. J. Med. Chem.,  2016, 117, 47-58.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.074] [PMID: 27089211] 
[201] 
Gajera, S.B.; Mehta, J.V.; Thakor, P.; Thakkar, V.R.; Chudasama, P.C.; Patel, J.S.; Patel, M.N. Half-sandwich iridiumIII complexes with pyrazole-substituted heterocyclic frameworks and their biological applications. RSC,  2016, 40, 9968-9980.
[http://dx.doi.org/10.1039/C6NJ02153K] 
[202] 
Liu, Y.N.; Wang, J.J.; Ji, Y.T.; Zhao, G.D.; Tang, L.Q.; Zhang, C.M.; Guo, X.L.; Liu, Z.P. Design, Synthesis, and Biological Evaluation of 1-Methyl-1,4-dihydroindeno[1,2-c]pyrazole Analogues as Potential Anticancer Agents Targeting Tubulin Colchicine Binding Site. J. Med. Chem.,  2016, 59(11), 5341-5355.
[http://dx.doi.org/10.1021/acs.jmedchem.6b00071] [PMID: 27172319] 
[203] 
Ai, T.; Willett, R.; Williams, J.; Ding, R.; Wilson, D.J.; Xie, J.; Kim, D.H.; Puertollano, R.; Chen, L.N. -(1-Benzyl-3,5-dimethyl-1H-pyrazol-4-yl)benzamides: Antiproliferative Activity and Effects on mTORC1 and Autophagy. ACS Med. Chem. Lett.,  2016, 8(1), 90-95.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00392] [PMID: 28105281] 
[204] 
Liang, X.; Zang, J.; Zhu, M.; Gao, Q.; Wang, B.; Xu, W.; Zhang, Y. Design, Synthesis, and Antitumor Evaluation of 4-Amino-(1H)-pyrazole Derivatives as JAKs Inhibitors. ACS Med. Chem. Lett.,  2016, 7(10), 950-955.
[http://dx.doi.org/10.1021/acsmedchemlett.6b00247] [PMID: 27774135] 
[205] 
Mor, S.; Nagoria, S.; Kumar, A.; Monga, J.; Lohan, S. Convenient synthesis, anticancer evaluation and QSAR studies of some thiazole tethered indenopyrazoles. Med. Chem. Res.,  2016, 25, 1096-1114.
[http://dx.doi.org/10.1007/s00044-016-1528-8] 
[206] 
Atmaca, H.; Özkan, A.N.; Zora, M. Novel ferrocenyl pyrazoles inhibit breast cancer cell viability via induction of apoptosis and inhibition of PI3K/Akt and ERK1/2 signaling. Chem. Biol. Interact.,  2017, 263, 28-35.
[http://dx.doi.org/10.1016/j.cbi.2016.12.010] [PMID: 27989600] 
[207] 
Wang, M.; Xu, S.; Lei, H.; Wang, C.; Xiao, Z.; Jia, S.; Zhi, J.; Zheng, P.; Zhu, W. Design, synthesis and antitumor activity of Novel Sorafenib derivatives bearing pyrazole scaffold. Bioorg. Med. Chem.,  2017, 25(20), 5754-5763.
[http://dx.doi.org/10.1016/j.bmc.2017.09.003] [PMID: 28927801] 
[208] 
Abdelgawad, M.A.; Bakr, R.B.; Omar, H.A. Design, synthesis and biological evaluation of some novel benzothiazole/benzoxazole and/or benzimidazole derivatives incorporating a pyrazole scaffold as antiproliferative agents. Bioorg. Chem.,  2017, 74, 82-90.
[http://dx.doi.org/10.1016/j.bioorg.2017.07.007] [PMID: 28772160] 
[209] 
Galal, S.A.; Khairat, S.H.M.; Ali, H.I.; Shouman, S.A.; Attia, Y.M.; Ali, M.M.; Mahmoud, A.E.; Abdel-Halim, A.H.; Fyiad, A.A.; Tabll, A.; El-Shenawy, R.; El Abd, Y.S.; Ramdan, R.; El Diwani, H.I.; Part, I.I. New candidates of pyrazole-benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors. Eur. J. Med. Chem.,  2017, 144, 859-873.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.023] [PMID: 29316526] 
[210] 
G, J.D.; Poornachandra, Y.; Ratnakar Reddy, K.; Naresh Kumar, R.; Ravikumar, N.; Krishna Swaroop, D.; Ranjithreddy, P.; Shravan Kumar, G.; Nanubolu, J.B.; Ganesh Kumar, C.; Narsaiah, B. Synthesis of novel pyrazolo[3,4-b]quinolinyl acetamide analogs, their evaluation for antimicrobial and anticancer activities, validation by molecular modeling and CoMFA analysis. Eur. J. Med. Chem.,  2017, 130, 223-239.
[http://dx.doi.org/10.1016/j.ejmech.2017.02.052] [PMID: 28254697] 
[211] 
Galal, S.A.; Abdelsamie, A.S.; Shouman, S.A.; Attia, Y.M.; Ali, H.I.; Tabll, A.; El-Shenawy, R.; El Abd, Y.S.; Ali, M.M.; Mahmoud, A.E.; Abdel-Halim, A.H.; Fyiad, A.A.; Girgis, A.S.; El-Diwani, H.I.; Part, I.; Part, I. Design, synthesis and biological evaluation of novel pyrazole-benzimidazole conjugates as checkpoint kinase 2 (Chk2) inhibitors with studying their activities alone and in combination with genotoxic drugs. Eur. J. Med. Chem.,  2017, 134, 392-405.
[http://dx.doi.org/10.1016/j.ejmech.2017.03.090] [PMID: 28433679] 
[212] 
Hura, N.; Naaz, A.; Prassanawar, S.S.; Guchhait, S.K.; Panda, D. Drug-Clinical Agent Molecular Hybrid: Synthesis of Diaryl(trifluoromethyl)pyrazoles as Tubulin Targeting Anticancer Agents. ACS Omega,  2018, 3(2), 1955-1969.
[http://dx.doi.org/10.1021/acsomega.7b01784] [PMID: 30023819] 
[213] 
Allam, M.; Bhavani, A.K.D.; Mudiraj, A.; Ranjan, N.; Thippana, M.; Babu, P.P. Synthesis of pyrazolo[3,4-d]pyrimidin-4(5H)-ones tethered to 1,2,3-triazoles and their evaluation as potential anticancer agents. Eur. J. Med. Chem.,  2018, 156, 43-52.
[http://dx.doi.org/10.1016/j.ejmech.2018.06.055] [PMID: 30006173] 
[214] 
El-Gamal, M.I.; Park, B.J.; Oh, C.H. Synthesis, in vitro antiproliferative activity, and kinase inhibitory effects of pyrazole-containing diarylureas and diarylamides. Eur. J. Med. Chem.,  2018, 156, 230-239.
[http://dx.doi.org/10.1016/j.ejmech.2018.07.008] [PMID: 30006168] 
[215] 
Harras, M.F.; Sabour, R. Design, synthesis and biological evaluation of novel 1,3,4-trisubstituted pyrazole derivatives as potential chemotherapeutic agents for hepatocellular carcinoma. Bioorg. Chem.,  2018, 78, 149-157.
[http://dx.doi.org/10.1016/j.bioorg.2018.03.014] [PMID: 29567429] 
[216] 
Akhtar, M.J.; Khan, A.A.; Ali, Z.; Dewangan, R.P.; Rafi, M.; Hassan, M.Q.; Akhtar, M.S.; Siddiqui, A.A.; Partap, S.; Pasha, S.; Yar, M.S. Synthesis of stable benzimidazole derivatives bearing pyrazole as anticancer and EGFR receptor inhibitors. Bioorg. Chem.,  2018, 78, 158-169.
[http://dx.doi.org/10.1016/j.bioorg.2018.03.002] [PMID: 29571113] 
[217] 
Ren, S.Z.; Wang, Z.C.; Zhu, D.; Zhu, X.H.; Shen, F.Q.; Wu, S.Y.; Chen, J.J.; Xu, C.; Zhu, H.L. Design, synthesis and biological evaluation of novel ferrocene-pyrazole derivatives containing nitric oxide donors as COX-2 inhibitors for cancer therapy. Eur. J. Med. Chem.,  2018, 157, 909-924.
[http://dx.doi.org/10.1016/j.ejmech.2018.08.048] [PMID: 30149323] 
[218] 
Verma, G.; Chashoo, G.; Ali, A.; Khan, M.F.; Akhtar, W.; Ali, I.; Akhtar, M.; Alam, M.M.; Shaquiquzzaman, M. Synthesis of pyrazole acrylic acid based oxadiazole and amide derivatives as antimalarial and anticancer agents. Bioorg. Chem.,  2018, 77, 106-124.
[http://dx.doi.org/10.1016/j.bioorg.2018.01.007] [PMID: 29353728] 
[219] 
Khan, I.; Garikapati, K.R.; Shaik, A.B.; Makani, V.K.K.; Rahim, A.; Shareef, M.A.; Reddy, V.G.; Pal-Bhadra, M.; Kamal, A.; Kumar, C.G. Design, synthesis and biological evaluation of 1, 4-dihydro indeno[1,2-c] pyrazole linked oxindole analogues as potential anticancer agents targeting tubulin and inducing p53 dependent apoptosis. Eur. J. Med. Chem.,  2018, 144, 104-115.
[http://dx.doi.org/10.1016/j.ejmech.2017.12.010] [PMID: 29268127] 
[220] 
Dai, H.; Ge, S.; Guo, J.; Chen, S.; Huang, M.; Yang, J.; Sun, S.; Ling, Y.; Shi, Y. Development of novel bis-pyrazole derivatives as antitumor agents with potent apoptosis induction effects and DNA damage. Eur. J. Med. Chem.,  2018, 143, 1066-1076.
[http://dx.doi.org/10.1016/j.ejmech.2017.11.098] [PMID: 29232583] 
[221] 
Metwally, N.H.; Deeb, E.A. Synthesis, anticancer assessment on human breast, liver and colon carcinoma cell lines and molecular modeling study using novel pyrazolo[4,3-c]pyridine derivatives. Bioorg. Chem.,  2018, 77, 203-214.
[http://dx.doi.org/10.1016/j.bioorg.2017.12.032] [PMID: 29367077] 
[222] 
Mohamed, S.A. EI-Gaby.; Ghorab, M.M; Ismail, Z.H.; Abdel-Gawad, S.M.; Aly, H.M. Synthesis, structural characterization and anticancer evaluation of pyrazole derivatives. Med. Chem. Res.,  2018, 27, 72-79.
[http://dx.doi.org/10.1007/s00044-017-2035-2] 
[223] 
Sar, D.; Srivastava, I.; Misra, S.K.; Ostadhossein, F.; Fathi, P.; Pan, D. Copper-catalyzed syntheses of pyrene-pyrazole pharmacophores and structure activity studies for tubulin polymerization. ACS Omega,  2018, 3(6), 6378-6387.
[http://dx.doi.org/10.1021/acsomega.8b00320] [PMID: 30221233] 
[224] 
Ran, F.; Liu, Y.; Zhang, D.; Liu, M.; Zhao, G. Discovery of novel pyrazole derivatives as potential anticancer agents in MCL. Bioorg. Med. Chem. Lett.,  2019, 29(9), 1060-1064.
[http://dx.doi.org/10.1016/j.bmcl.2019.03.005] [PMID: 30857748] 
[225] 
Romagnoli, R.; Oliva, P.; Salvador, M.K.; Camacho, M.E.; Padroni, C.; Brancale, A.; Ferla, S.; Hamel, E.; Ronca, R.; Grillo, E.; Bortolozzi, R.; Rruga, F.; Mariotto, E.; Viola, G. Design, synthesis and biological evaluation of novel vicinal diaryl-substituted 1H-Pyrazole analogues of combretastatin A-4 as highly potent tubulin polymerization inhibitors. Eur. J. Med. Chem.,  2019, 181, 111577-111597.
[http://dx.doi.org/10.1016/j.ejmech.2019.111577] [PMID: 31400707] 
[226] 
Mohamed, T.K.; Batran, R.Z.; Elseginy, S.A.; Ali, M.M.; Mahmoud, A.E. Synthesis, anticancer effect and molecular modeling of new thiazolylpyrazolyl coumarin derivatives targeting VEGFR-2 kinase and inducing cell cycle arrest and apoptosis. Bioorg. Chem.,  2019, 85, 253-273.
[http://dx.doi.org/10.1016/j.bioorg.2018.12.040] [PMID: 30641320] 
[227] 
Cui, Y.J.; Tang, L.Q.; Zhang, C.M.; Liu, Z.P. Synthesis of novel pyrazole derivatives and their tumor cell growth inhibitory activity. Molecules,  2019, 24(2), 279-287.
[http://dx.doi.org/10.3390/molecules24020279] [PMID: 30642134] 
[228] 
Yamali, C.; Gul, H.I.; Ece, A.; Bua, S.; Angeli, A.; Sakagami, H.; Sahin, E.; Supuran, C.T. Synthesis, biological evaluation and in silico modelling studies of 1,3,5-trisubstituted pyrazoles carrying benzenesulfonamide as potential anticancer agents and selective cancer-associated hCA IX isoenzyme inhibitors. Bioorg. Chem.,  2019, 92, 103222-103234.
[http://dx.doi.org/10.1016/j.bioorg.2019.103222] [PMID: 31499260] 
[229] 
Wang, Y.T.; Shi, T.Q.; Zhu, H.L.; Liu, C.H. Synthesis, biological evaluation and molecular docking of benzimidazole grafted benzsulfamide-containing pyrazole ring derivatives as novel tubulin polymerization inhibitors. Bioorg. Med. Chem.,  2019, 27(3), 502-515.
[http://dx.doi.org/10.1016/j.bmc.2018.12.031] [PMID: 30606674] 
[230] 
Nagaraju, B.; Kovvuri, J.; Kumar, C.G.; Routhu, S.R.; Shareef, M.A.; Kadagathur, M.; Adiyala, P.R.; Alavala, S.; Nagesh, N.; Kamal, A. Synthesis and biological evaluation of pyrazole linked benzothiazole-β-naphthol derivatives as topoisomerase I inhibitors with DNA binding ability. Bioorg. Med. Chem.,  2019, 27(5), 708-720.
[http://dx.doi.org/10.1016/j.bmc.2019.01.011] [PMID: 30679134] 
[231] 
Dai, H.; Huang, M.; Qian, J.; Liu, J.; Meng, C.; Li, Y.; Ming, G.; Zhang, T.; Wang, S.; Shi, Y.; Yao, Y.; Ge, S.; Zhang, Y.; Ling, Y. Excellent antitumor and antimetastatic activities based on novel coumarin/pyrazole oxime hybrids. Eur. J. Med. Chem.,  2019, 166, 470-479.
[http://dx.doi.org/10.1016/j.ejmech.2019.01.070] [PMID: 30739827] 
[232] 
Ali, G.M.E.; Ibrahim, D.A.; Elmetwali, A.M.; Ismail, N.S.M. Design, synthesis and biological evaluation of certain CDK2 inhibitors based on pyrazole and pyrazolo[1,5-a] pyrimidine scaffold with apoptotic activity. Bioorg. Chem.,  2019, 86, 1-14.
[http://dx.doi.org/10.1016/j.bioorg.2019.01.008] [PMID: 30682722] 
[233] 
Gezegen, H.; Tutar, U.; Hepokur, C.; Ceylan, M. Synthesis and biological evaluation of novel indenopyrazole derivatives. J. Biochem. Mol. Toxicol.,  2019, 33(5), e22285.
[http://dx.doi.org/10.1002/jbt.22285] [PMID: 30672630] 
[234] 
Thangarasu, P.; Manikandan, A.; Thamaraiselvi, S. Discovery, synthesis and molecular corroborations of medicinally important novel pyrazoles; drug efficacy determinations through in silico, in vitro and cytotoxicity validations. Bioorg. Chem.,  2019, 86, 410-419.
[http://dx.doi.org/10.1016/j.bioorg.2019.02.003] [PMID: 30769266] 
[235] 
Omran, D.M.; Ghaly, M.A.; El-Messery, S.M.; Badria, F.A.; Abdel-Latif, E.; Shehata, I.A. Targeting hepatocellular carcinoma: Synthesis of new pyrazole-based derivatives, biological evaluation, DNA binding, and molecular modeling studies. Bioorg. Chem.,  2019, 88, 102917-102928.
[http://dx.doi.org/10.1016/j.bioorg.2019.04.011] [PMID: 30981111] 
[236] 
Reddy, V.G.; Reddy, T.S.; Jadala, C.; Reddy, M.S.; Sultana, F.; Akunuri, R.; Bhargava, S.K.; Wlodkowic, D.; Srihari, P.; Kamal, A. Pyrazolo-benzothiazole hybrids: Synthesis, anticancer properties and evaluation of antiangiogenic activity using in vitro VEGFR-2 kinase and in vivo transgenic zebrafish model. Eur. J. Med. Chem.,  2019, 182, 111609-111623.
[http://dx.doi.org/10.1016/j.ejmech.2019.111609] [PMID: 31445229] 
[237] 
Deshineni, R.; Arya, C.G.; Banothu, J.; Velpula, R.; Chellamella, G. Synthesis, anticancer and antibacterial evaluation of novel 1,3-diubstituted-1H-pyrazole-4-yl-methylene embedded fused thiazolo[2,3-b]quinazolinones. Chem. Data collect,  2020, 30, 100546-100566.
[238] 
Dawood, D.H.; Nossier, E.S.; Ali, M.M.; Mahmoud, A.E. Synthesis and molecular docking study of new pyrazole derivatives as potent anti-breast cancer agents targeting VEGFR-2 kinase. Bioorg. Chem.,  2020, 101, 103916-103954.
[http://dx.doi.org/10.1016/j.bioorg.2020.103916] [PMID: 32559576] 
[239] 
Bhirud, J.D.; Patil, R.D.; Narkhede, H.P. Sulfamic acid catalyzed synthesis of new 3,5-[(sub)phenyl]-1H-pyrazole bearing N1-isonicotinoyl: And their pharmacological activity evaluation. Bioorg. Med. Chem. Lett.,  2020, 30(23), 127558-127562.
[http://dx.doi.org/10.1016/j.bmcl.2020.127558] [PMID: 32961321] 
[240] 
Philoppes, J.N.; Khedr, M.A.; Hassan, M.H.A.; Kamel, G.; Lamie, P.F. New pyrazolopyrimidine derivatives with anticancer activity: Design, synthesis, PIM-1 inhibition, molecular docking study and molecular dynamics. Bioorg. Chem.,  2020, 100, 103944-103955.
[http://dx.doi.org/10.1016/j.bioorg.2020.103944] [PMID: 32450389] 
[241] 
Li, G.; Wang, Y.; Li, L.; Ren, Y.; Deng, X.; Liu, J.; Wang, W.; Luo, M.; Liu, S.; Chen, J. Design, synthesis, and bioevaluation of pyrazolo[1,5-a]pyrimidine derivatives as tubulin polymerization inhibitors targeting the colchicine binding site with potent anticancer activities. Eur. J. Med. Chem.,  2020, 202, 112519-11258.
[http://dx.doi.org/10.1016/j.ejmech.2020.112519] [PMID: 32650183] 
[242] 
Zimnitskiy, N.S.; Barkov, A.Y.; Ulitko, M.V.; Kutyashev, I.B.; Korotaev, V.Y.; Sosnovskikh, V.Y. An expedient synthesis of novel spiro[indenoquinoxalinepyrrolizidine]‒pyrazole conjugates with anticancer activity from 1,5-diarylpent-4-ene-1,3-diones through 1,3-dipolar cycloaddition/cyclocondensation sequence. New J. Chem.,  2020, 44, 16185-16199.
[http://dx.doi.org/10.1039/D0NJ02817G] 
[243] 
Gorle, S.; Gangu, K.K.; Maddila, S.; Jonnalagadda, S.B. Synthesis and anticancer activity of pyrazolo[4′, 3′:5,6]pyrano[2,3-d] pyrimidin-5(2H)-one derivatives. Chem. Data Collect,  2020, 41, 100471-100483.
[http://dx.doi.org/10.1016/j.cdc.2020.100471] 
[244] 
Bansal, K.K.; Bhardwaj, J.K.; Saraf, P.; Thakur, V.K.; Sharma, P.C. Synthesis of thiazole clubbed pyrazolederivetives as apoptosis inducers and anti-infective agents. Mater. Today Chem,  2020, 17, 100335-100344.
[http://dx.doi.org/10.1016/j.mtchem.2020.100335] 
[245] 
Wang, G.; Liu, W.; Peng, Z.; Huang, Y.; Gong, Z.; Li, Y. Design, synthesis, molecular modeling, and biological evaluation of pyrazole-naphthalene derivatives as potential anticancer agents on MCF-7 breast cancer cells by inhibiting tubulin polymerization. Bioorg. Chem.,  2020, 103, 104141-104149.
[http://dx.doi.org/10.1016/j.bioorg.2020.104141] [PMID: 32750611] 
[246] 
Kumar, S.; Lathwal, E.; Kumar, G.; Saroha, B.; Kumar, S.; Mahata, S.; Sahoo, P.K. Synthesis of pyrazole based novel aurone analogs and their cytotoxic activity against MCF-7 cell line. Chem. Data Collect,  2020, 30, 100559-100578.
[http://dx.doi.org/10.1016/j.cdc.2020.100559] 
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DOI https://dx.doi.org/10.2174/1389557521666210325115218	Print ISSN 1389-5575
Publisher Name Bentham Science Publisher	Online ISSN 1875-5607
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