Synlett 2013; 24(13): 1599-1605
DOI: 10.1055/s-0033-1339284
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© Georg Thieme Verlag Stuttgart · New York

Recent Developments in the Synthesis of Bioactive 2,4,6-Trisubstituted 1,3,5-Triazines

Ranjan Banerjee
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA   Fax: +1(617)5522705   Email: eranthie@bc.edu
,
Douglas R. Brown
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA   Fax: +1(617)5522705   Email: eranthie@bc.edu
,
Eranthie Weerapana*
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA   Fax: +1(617)5522705   Email: eranthie@bc.edu
› Author Affiliations
Further Information

Publication History

Received: 14 May 2013

Accepted after revision: 23 May 2013

Publication Date:
27 June 2013 (online)


Abstract

1,3,5-Triazine derivatives have widespread applications in the pharmaceutical, material, and agrochemical industries. In the biological arena, small-molecule libraries of 2,4,6-trisubstituted 1,3,5-triazines have yielded selective and potent chemical probes for diverse protein families. The structural symmetry and ease of functionalization of the 1,3,5-triazine core renders it a powerful scaffold for the rapid generation of diverse molecular libraries. Numerous synthetic routes, both solid-phase and solution-phase, have been developed to arrive at alkyl/aryl amino- and oxy-substituted triazine libraries. Here, we feature a subset of the recent synthetic advances towards generating 2,4,6-trisubstituted 1,3,5-triazines and highlight biologically active compounds that have resulted from these endeavors.

 
  • References

  • 1 Bartholomew D In Comprehensive Heterocyclic Chemistry II . Vol. 6. Katritzky AR, Rees CW. Pergamon; Oxford: 1996: 575-636
  • 2 von Angerer S In Science of Synthesis . Vol. 17. Weinreb SM. Georg Thieme Verlag; Stuttgart: 2004: 449
    • 3a Ono M, Kawahara N, Goto D, Wakabayashi Y, Ushiro S, Yoshida S, Izumi H, Kuwano M, Sato Y. Cancer Res. 1996; 56: 1512
    • 3b Foster BJ, Harding BJ, Leyland-Jones B, Hoth D. Cancer Treatment Reviews 1986; 13: 197
    • 3c Davey P, Tudhope GR. British Med. J. 1983; 287: 110
    • 3d Draber W, Tietjen K, Kluth JF, Trebst A. Angew. Chem. Int. Ed. Engl. 1991; 30: 1621
  • 4 Lee CR, Faulds D. Drugs 1995; 49: 932
  • 5 Sathiakumar N, MacLennan PA, Mandel J, Delzell E. Crit. Rev. Toxicol. 2011; 41 (01) 1
  • 6 Dalal RP, Goldfarb DS. Nat. Rev. Nephrol. 2011; 7: 267
    • 7a Moon HS, Jacobson EM, Khersonsky SM, Luzung MR, Walsh DP, Xiong W, Lee JW, Parikh PB, Lam JC, Kang TW, Rosania GR, Schier AF, Chang YT. J. Am. Chem. Soc. 2002; 124: 11608
    • 7b Khersonsky SM, Jung DW, Kang TW, Walsh DP, Moon HS, Jo H, Jacobson EM, Shetty V, Neubert TA, Chang YT. J. Am. Chem. Soc. 2003; 125: 11804
    • 7c Kim JY, Lee JW, Lee WS, Ha HH, Vendrell M, Bork JT, Lee Y, Chang YT. ACS Comb. Sci. 2012; Vol 14: 395
    • 7d Courme C, Gresh N, Vidal M, Lenoir C, Garbay C, Florent JC, Bertounesque E. Eur. J. Med. Chem. 2010; 45: 244
    • 7e Uttamchandani M, Walsh DP, Khersonsky SM, Huang X, Yao SQ, Chang YT. J. Comb. Chem. 2004; 6: 862
    • 7f Hu Z, Ma T, Chen Z, Ye Z, Zhang G, Lou Y, Yu Y. J. Comb. Chem. 2009; 11: 267
    • 7g Clark MA, Acharya RA, Arico-Muendel CC, Belyanskaya SL, Benjamin DR, Carlson NR, Centrella PA, Chiu CH, Creaser SP, Cuozzo JW, Davie CP, Ding Y, Franklin GJ, Franzen KD, Gefter ML, Hale SP, Hansen NJ, Israel DI, Jiang J, Kavarana MJ, Kelley MS, Kollmann CS, Li F, Lind K, Mataruse S, Medeiros PF, Messer JA, Myers P, O’Keefe H, Oliff MC, Rise CE, Satz AL, Skinner SR, Svendsen JL, Tang L, van Vloten K, Wagner RW, Yao G, Zhao B, Morgan BA. Nat. Chem. Biol. 2009; 5: 647
    • 7h Wang S, Lee WS, Ha HH, Chang YT. Org. Biomol. Chem. 2011; 9: 6924
    • 8a Saripinar E, Gecen N, Sahin K, Yanmaz E. Eur. J. Med. Chem. 2010; 45: 4157
    • 8b Hysell M, Siegel JS, Tor Y. Org. Biomol. Chem. 2005; 3: 2946
  • 9 Fowler PW, Steiner E. J. Phys. Chem. A 1997; 101: 1409
  • 10 Blotny G. Tetrahedron 2006; 62: 9507
  • 11 Cuthbertson WW, Moffatt JS. J. Chem. Soc. 1948; 561
    • 12a Stankova M, Lebl M. Mol. Diversity 1996; 2: 75
    • 12b Hoesl CE, Nefzi A, Houghten RA. J. Comb. Chem. 2003; 5: 155
  • 13 Bork JT, Lee JW, Khersonsky SM, Moon HS, Chang YT. Org. Lett. 2003; 5: 117
  • 14 Banerjee R, Pace NJ, Brown DR, Weerapana E. J. Am. Chem. Soc. 2013; 135: 2497
  • 15 Rostovtsev VV, Green LG, Fokin VV, Sharpless KB. Angew. Chem. Int. Ed. 2002; 41: 2596
    • 16a Gopalsamy A, Yang H. J. Comb. Chem. 2001; 3: 278
    • 16b Lippa KA, Roberts AL. Environ. Sci. Technol. 2002; 36: 2008
  • 17 Saleh M, Abbott S, Perron V, Lauzon C, Penney C, Zacharie B. Bioorg. Med. Chem. Lett. 2010; 20: 945
  • 18 Peng Z, Haag BA, Knochel P. Org. Lett. 2010; 12: 5398
  • 19 Gulevskaya AV, Maes BU. W, Meyers C. Synlett 2007; 71