Citation: Xin-Jian Song, Ping Yang, Hui Gao, Yan Wang, Xing-Gao Dong, Xiao-Hong Tan. Facile synthesis and antitumor activity of novel 2-trifl uoromethylthieno[2,3-d]pyrimidine derivatives[J]. Chinese Chemical Letters, ;2014, 25(7): 1006-1010. doi: 10.1016/j.cclet.2014.05.043 shu

Facile synthesis and antitumor activity of novel 2-trifl uoromethylthieno[2,3-d]pyrimidine derivatives

Xin-Jian Song ^a,b,, ,
Ping Yang ^a ,
Hui Gao ^a ,
Yan Wang ^a,, ,
Xing-Gao Dong ^a ,
Xiao-Hong Tan ^a,b

1.
a Key Laboratory of Biologic Resources Protection and Utilization of Hubei Province, Hubei Minzu University, Enshi 445000, China;
2.
b College of Forestry and Horticulture, Hubei Minzu University, Enshi 445000, China

Corresponding author: Xin-Jian Song, Yan Wang,
Received Date: 9 April 2014
Available Online: 21 May 2014
Fund Project: This work was financially supported by the National Natural Science Foundation of China (No. 21262012) (No. 21262012)

A series of novel 2-trifluoromethylthieno[2,3-d]pyrimidine derivatives were synthesized by a facile three-step procedure that afforded advantages of mild reaction conditions, simple protocol and good yields. The structures of the final compounds were confirmed by IR, NMR, EI-MS, elemental analysis, and X-ray diffraction. Preliminary bioassay results showed that some of the analogs exhibit excellent antitumor activity against MCF-7 and HepG2, especially compounds 3a, 3b, 3e and 3h exhibited higher activity than the positive control gefitinib.
- Thieno[2,3-d]pyrimidine,
- Gewald reaction,
- Trifluoromethyl,
- Facile synthesis,
- Antitumor activity
1. [1]
  [1] R. Adepu, D. Rambabu, B. Prasad, et al., Novel thieno[2,3-d]pyrimidines: their design, synthesis, crystal structure analysis and pharmacological evaluation, Org. Biomol. Chem. 10 (2012) 5554-5569.
2. [2]
  [2] J.G. Paez, P.A. Janne, J.C. Lee, et al., EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy, Science 304 (2004) 1497-1500.
3. [3]
  [3] B. Higgins, K. Kolinsky, M. Smith, et al., Antitumor activity of erlotinib (OSI-774, Tarceva) alone or in combination in human non-small cell lung cancer tumor xenograft models, Anticancer Drugs 15 (2004) 503-512.
4. [4]
  [4] Z.A. Liu, A. Fusi, A. Schmittel, et al., Eradication of EGFR-positive circulating tumor cells and objective tumor response with lapatinib and capecitabine, Cancer Biol. Ther. 10 (2010) 860-864.
5. [5]
  [5] Y. Dai, Y. Guo, R.R. Frey, et al., Thienopyrimidine ureas as novel and potent multitargeted receptor tyrosine kinase inhibitors, J. Med. Chem. 48 (2005) 6066-6083.
6. [6]
  [6] J.C. Aponte, A.J. Vaisberg, D. Castillo, et al., Trypanoside, anti-tuberculosis, leishmanicidal, and cytotoxic activities of tetrahydrobenzothienopyrimidines, Bioorg. Med. Chem. 18 (2010) 2880-2886.
7. [7]
  [7] N.S. Habib, R. Soliman, A.A. El-Tombary, S.A. El-Hawash, O.G. Shaaban, Synthesis and biological evaluation of novel series of thieno[2,3-d]pyrimidine derivatives as anticancer and antimicrobial agents, Med. Chem. Res. 22 (2013) 3289-3308.
8. [8]
  [8] B.Q. Cai, H.X. Jin, X.J. Yan, P. Zhu, G.X. Hu, 3D-QSAR and 3D-QSSR studies of thieno[2,3-d]pyrimidin-4-yl hydrazone analogues as CDK4 inhibitors by CoMFA analysis, Acta Pharmacol. Sin. 35 (2014) 151-160.
9. [9]
  [9] W.K. Hagmann, The many roles for fluorine in medicinal chemistry, J. Med. Chem. 51 (2008) 4359-4369.
10. [10]
  [10] X.J. Song, Z.C. Duan, Y. Shao, X.G. Dong, Facile synthesis of novel fluorinated thieno[2,3-d]pyrimidine derivatives containing 1,3,4-thiadiazole, Chin. Chem. Lett. 23 (2012) 549-552.
11. [11]
  [11] T. Horiuchi, M. Nagata, M. Kitagawa, K. Akahane, K. Uoto, Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: synthesis, biological evaluation and structure-activity relationships. Part 2, Bioorg. Med. Chem. Lett. 17 (2009) 7850-7860.
12. [12]
  [12] A.G. Golub, V.G. Bdzohla, N.V. Briukhovetska, et al., Synthesis and biological evaluation of substituted (thieno[2,3-d]pyrimidin-4-ylthio)carboxylic acids as inhibitors of human protein kinase CK2, Eur. J. Med. Chem. 46 (2011) 870-876.
13. [13]
  [13] T. Beckers, A. Sellmer, E. Eichhorn, et al., Novel inhibitors of epidermal growth factor receptor: (4-(arylamino)-7H-pyrrolo[2,3-d]pyrimidin-6-yl)(1H-indol-2-yl)methanones and (1H-indol-2-yl)(4-(phenylamino)thieno[2,3-d]pyrimidin-6-yl)methanones, Bioorg. Med. Chem. 20 (2012) 125-136.
14. [14]
  [14] S.E. Abbas, N.M.A. Gawad, R.F. George, Y.A. Akar, Synthesis, antitumor and antibacterial activities of some novel tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidine derivatives, Eur. J. Med. Chem. 65 (2013) 195-204.
15. [15]
  [15] P. Yang, Y. Wang, Z.C. Duan, et al., Synthesis, crystal structure, and biological activity of 4-chlorobenzaldehyde (2-trifluoromethyl-5,6,7,8-tetrahydrobenzo[ 4,5]thieno[2,3-d]pyrimidin-4-yl)hydrazone monohydrate, Chin. J. Struct. Chem. 32 (2013) 1023-1030.
16. [16]
  [16] T. Horiuchi, J. Chiba, K. Uoto, T. Soga, Discovery of novel thieno[2,3-d]pyrimidin-4-yl hydrazone-based inhibitors of Cyclin D1-CDK4: synthesis, biological evaluation, and structure-activity relationships, Bioorg. Med. Chem. Lett. 19 (2009) 305-308.
17. [17]
  [17] R.J. Gillespie, D.R. Adams, D. Bebbington, et al., Antagonists of the human adenosine A_2A receptor. Part 1: discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives, Bioorg. Med. Chem. Lett. 18 (2008) 2916-2919.
18. [18]
  [18] M. Hayakawa, H. Kaizawa, H. Moritomo, et al., Synthesis and biological evaluation of 4-morpholino-2-phenylquinazolines and related derivatives as novel PI3 kinase p110a inhibitors, Bioorg. Med. Chem. 14 (2006) 6847-6858.
19. [19]
  [19] M.R. Prasad, D.P. Kishore, Multistep, microwave assisted, solvent free synthesis and antibacterial activity of 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines, Chem. Pharm. Bull. 55 (2007) 776-779.
20. [20]
  [20] A.E. Kassab, E.M. Gedawy, Synthesis and anticancer activity of novel 2-pyridyl hexahyrocyclooctathieno[2,3-d]pyrimidine derivatives, Eur. J. Med. Chem. 63 (2013) 224-230.
21. [21]
  [21] M. Sridhar, R.M. Rao, N.H.K. Baba, R.M. Kumbhare, Microwave-accelerated Gewald reaction: synthesis of 2-aminothiophenes, Tetrahedron Lett. 48 (2007) 3171-3172.
22. [22]
  [22] R. Rajagopal, T.M. Jyothi, T. Daniel, K.V. Srinivasan, B.S. Rao, Calcined Mg-Al hydrotalcite as a heterogeneous base catalyst for Gewald aminothiophene synthesis, Synth. Commun. 31 (2001) 3113-3117.
23. [23]
  [23] T. Wang, X.G. Huang, J. Liu, et al., An efficient one-pot synthesis of substituted 2-aminothiophenes via three-component Gewald reaction catalyzed by L-proline, Synlett (2010) 1351-1354.
24. [24]
  [24] D.D. Zhao, L. Li, F. Xu, Q. Wu, X.F. Lin, Bovine serum albumin-catalyzed one-pot synthesis of 2-aminothiophenes via Gewald reaction, J. Mol. Catal. B-Enzym. 95 (2013) 29-35.
25. [25]
  [25] R. Tayebee, F. Javadi, G. Argi, Easy single-step preparation of ZnO nano-particles by sedimentation method and studying their catalytic performance in the synthesis of 2-aminothiophenes via Gewald reaction, J. Mol. Catal. A-Chem. 368-369 (2013) 16-23.
26. [26]
  [26] E. Rezaei-Seresht, R. Tayebee, M. Yasemi, KG-60-piperazine as a new heterogeneous catalyst for Gewald three-component reaction, Synth. Commun. 43 (2013) 1859-1864.
27. [27]
  [27] P. Malherbe, R. Masciadri, R.D. Norcross, H. Ratni, A.W. Thomas, Thieno-pyridine derivatives as allosteric enhancers of the GABAB receptors, US2006135552 (2006).
28. [28]
  [28] G.M. Sheldrick, A short history of SHELX, Acta Cryst. A64 (2008) 112-122.
29. [29]
  [29] M.C. Alley, D.A. Scudiero, A. Monks, et al., Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay, Cancer Res. 48 (1988) 589-601.
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