Abstract
The reaction of cyanoacetylhydrazine (1) with acetylchloride (2) gave the N-acyl derivative 3. The latter underwent ready cyclization in sodium ethoxide to give the pyrazole derivative 4 which was the key compound for the synthesis of thiophene, thieno[2,3-b]pyridine, and thiazole derivatives. The anti-tumor evaluations of the newly synthesized products against the three human tumor cell lines, namely, breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460), and CNS cancer (SF-268), were studied. Some of these compounds were found to exhibit much higher inhibitory effects toward the three tumor cell lines than the reference doxorubicin. Molecular modeling of the four compounds 12c, 12f, 16a, and 16d, which showed the maximum inhibitory effect, were done.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abadi AH, Abdel Haleem Eissa Hassan A, Hassan GS (2003) Chem Pharm Bul 51:838–844
Al-Said MS, Bashandy MS, Al-gasoumi SI, Ghorab MM (2011) Anti-breast cancer activity of some novel 1,2-dihydropyridine, thiophene and thiazole derivatives. Eur J Med Chem 46(1):137–141
Bondock S, Fadaly W, Metwally MA (2010) Synthesis and antimicrobial activity of some new thiazole, thiophene and pyrazole derivatives containing benzothiazole moiety. Eur J Med Chem 45(9):3692–3701
Brasca MG, Albanese C, Amici R, Ballinari D, Corti L, Croci V, Fancelli D, Fiorentini F, Nesi M, Orsini P, Orzi F, Pastori W, Perrone E, Pesenti E, Pevarello P, Riccardi-Sirtori F, Roletto F, Roussel P, Varasi M, Vulpetti A, Mercurio C (2007) 6-Substituted pyrrolo[3,4-c]pyrazoles: an improved class of CDK2 inhibitors. Chem Med Chem 2:841–852
Cho N, Kamaura M, Yogo T, Imoto H (2009) PCT Int Appl WO 2009139340
Dugi K, Mark M, Himmelsbach F (2009) PCT Int Appl WO 2009022009
Elguero J, Goya P, Jagerovic N, Silva AMS (2002) In: Attanasi OA, Spinelli D (eds) Targets in heterocyclic systems, 6th edn. Società Chimica Italiana, Roma, pp 52–98
Fadda AA, Abdel-Latif E, El-Mekawy RE (2009) Synthesis and molluscicidal activity of some new thiophene, thiadiazole and pyrazole derivatives. Eur J Med Chem 44(3):1250–1256
Gouda MA, Berghot MA, Abd El-Ghani GE, khalil AM (2010) Synthesis and antimicrobial activities of some new thiazole and pyrazole derivatives based on 4,5,6,7-tetrahydrobenzothiophene moiety. Eur J Med Chem 45(4):1338–1345
Insuasty B, Tigreros A, Orozco F, Quiroga J, Abonia R, Nogueras M, Khalil AM, Berghot MA, Gouda MA (2009) Synthesis and antibacterial activity of some new thiazole and thiophene derivatives. Eur J Med Chem 44(11):4434–4440
Labbozzetta M, Baruchello R, Marchetti P, Gueli MC, Poma P, Notarbartolo M, Simoni D, D’Alessandro N (2009) Lack of nucleophilic addition in the isoxazole and pyrazole diketone modified analogs of curcumin; implications for their antitumor and chemosensitizing activities. Chem Biol Interact 181:29–36
Ludwig S, Planz O, Sedlacek HH, Pleschka S (2004) PCT Int Appl WO12
Hubbard SR, Till JH (2000) Rev Biochem 69(373):2004085682
Michaelides MR (2010) PCT Int Appl WO 2010065825
Momose Y, Maekawa T, Odaka H, Kimura H (2001) PCT Int Appl WO 2001038325
Perchellet EM, Ward MM, Skaltsounis AL, Kostakis IK, Pouli N, Marakos P, Perchellet JP (2006) Antiproliferative and proapoptotic activities of pyranoxanthenones, pyranothioxanthenones, and their pyrazole-fused derivatives in HL-60 cells. Anticancer Res 26:2791–2804
Pevarello P, Brasca MG, Amici R, Orsini P, Traquandi G, Corti L, Piutti C, Sansonna P, Villa M, Pierce BS, Pulici M, Giordano P, Martina K, Fritzen EL, Nugent RA, Casale E, Cameron A, Ciomei M, Roletto F, Isacchi A, Fogliatto G, Pesenti E, Pastori W, Marsiglio A, Leach KL, Clare PM, Fiorentini F, Varasi M, Vulpetti A, Warpehoski MA (2004) 3-Aminopyrazole inhibitors of CDK2/cyclin A as antitumor agents. 1. Lead finding. J Med Chem 47:3367–3380
Pevarello P, Fancelli D, Vulpetti A, Amici R, Villa M, Pittalà V, Vianello P, Cameron A, Ciomei M, Mercurio C, Bischoff JR, Roletto F, Varasi M, Brasca MG (2006) 3-Amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: a new class of CDK2 inhibitors. Bioorg Med Chem Lett 16:1084–1090
Regan J, Breitfelder S, Cirillo P, Gilmore T, Graham AG, Hickey E, Klaus B, Madwed J, Moriak M, Moss N, Pargellis C, Pav S, Proto A, Swinamer A, Tong L, Torcellini C (2002) Pyrazole urea-based inhibitors of p38 MAP kinase: from lead compound to clinical candidate. J Med Chem 45:2994–3008
Rida SM, Saudi MNS, Youssef AM, Halim MA (2009) Synthesis and biological evaluation of the pyrazole class of cyclooxygenase-2-inhibitors. Lett Org Chem 6:282–288
Sanchez A, Cobo J (2010) 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 18:4965–4974
Sunil Kumar YC, Sadashiva MP, Rangappa KS (2007) An efficient synthesis of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine: a potent M1 selective muscarinic agonist. Tetrahedron Lett 48:4565–4568
Szabo G, Fischer J, Kis-Varga A, Gyires K (2008) New celecoxib derivatives as anti-inflammatory agents. J Med Chem 51:142–147
Tanitame A, Oyamada Y, Ofuji K, Fujimoto M, Suzuki K, Ueda T, Terauchi H, Kawasaki M, Nagai K, Wachi M, Yamagishi J (2004) Synthesis and antibacterial activity of novel and potent DNA gyrase inhibitors with azole ring. Bioorg Med Chem 12:5515–5524
Tanitame A, Oyamada Y, Ofuji K, Terauchi H, Kawasaki M, Wachi M, Yamagishi J (2005) Synthesis and antibacterial activity of a novel series of DNA gyrase inhibitors: 5-[(E)-2-arylvinyl]pyrazoles. Bioorg Med Chem Lett 15:4299–4303
Acknowledgments
R. M. Mohareb would like to express his deepest thank to the Alexander von Humboldt Foundation in Bonn for affording his a fellowship in Germany, München during summer, 2012 for doing research and completing this work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mohareb, R.M., Abdallah, A.E.M. & Abdelaziz, M.A. New approaches for the synthesis of pyrazole, thiophene, thieno[2,3-b]pyridine, and thiazole derivatives together with their anti-tumor evaluations. Med Chem Res 23, 564–579 (2014). https://doi.org/10.1007/s00044-013-0664-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00044-013-0664-7