Guetzoyan, Lucie J., Spooner, Robert A. , Lord, Mike (J. Mike), Roberts, Lynne M. and Clarkson, Guy J.. (2010) Simple oxidation of pyrimidinylhydrazones to triazolopyrimidines and their inhibition of Shiga toxin trafficking. European Journal of Medicinal Chemistry, Vol.45 (No.1). pp. 275-283. ISSN 0223-5234

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Abstract

The oxidative cyclisation of a range of benzothieno[2,3-d]pyrimidine hydrazones (7a–j) to the 1,2,4-triazolo[4,3-c]pyrimidines (8a–j) catalysed by lithium iodide or to the 1,2,4-triazolo[1,5-c]pyrimidines (10a–j) with sodium carbonate is presented. A complementary synthesis of the 1,2,4-triazolo[1,5-c]pyrimidines starting from the amino imine 11 is also reported. The effect of these compounds on Shiga toxin (STx) trafficking in HeLa cells and comparison to the previously reported Exo2 is also detailed.

Item Type:	Journal Article
Subjects:	Q Science > QD Chemistry Q Science > QR Microbiology
Divisions:	Faculty of Science > Chemistry Faculty of Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Pyrimidines -- Research, Lithium compounds -- Research, Dimethyl sulfoxide, Gram-negative bacterial infections
Journal or Publication Title:	European Journal of Medicinal Chemistry
Publisher:	Elsevier Masson
ISSN:	0223-5234
Date:	January 2010
Volume:	Vol.45
Number:	No.1
Page Range:	pp. 275-283
Identification Number:	10.1016/j.ejmech.2009.10.007
Status:	Peer Reviewed
Access rights to Published version:	Restricted or Subscription Access
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC)
Grant number:	BB/E012450/1 (BBSRC)
References:	[1] M.R. Prasad, A.R. Rao, P.S. Rao, K.S. Rajan, S. Meena, K. Madhavi, Euro. J. Med. Chem. 43 (2008) 614–620. [2] V.H. Bhaskar; P.D Gokulan, Oriental J. Chem. 23 (2007) 999–1004. [3] a) L.D. Jennings, S.L. Kincaid, Y.D. Wang, G. Krishnamurthy, C F. Beyer, J.P. McGinnis, M. Miranda, C.M. Discafani, S. K. Rabindran, Bioorg. Med. Chem. Lett. 15 (2005) 4731–4735 b) H. Han, J. Roberts, O. Lou, W.A. Muller, N. Nathan, C. Nathan, J. Leukocyte Biol. 79 (2006) 147–154. [4] a) A.E. Rashad, M.A. Ali, Nucleoside, Nucleos. Nucleot. 25 (2006) 17-28. b) C.S. Thakur, B.K. Jha, B.Dong, J. Das Gupta, K.M. Silverman, H. Mao, H. Sawai, A.O. Nakamura, A K. Banerjee, A. Gudkov, R.H. Silverman, Proc. Natl. Acad. Sci. USA 104 (2007) 9585–9590. [5] a) Y. Dai, Y. Guo, R.R. Frey, Z. Ji, M.L. Curtin, A.A. Ahmed, D.H. Albert, L. Arnold, S.S. Arries, T. Barlozzari, J.L. Bauch, J.J. Bouska, P.F. Bousquet, G.A. Cunha, K.B. Glaser, J. Guo, J. Li, P.A. Marcotte, K.C. Marsh, M.D. Moskey, L.J. Pease, K.D. Stewart, V.S. Stoll, P. Tapang, N. Wishart, S.K. Davidsen, and M.R. Michaelides, J. Med. Chem. 48 (2005) 6066–6083. b) M.S. Phoujdar, M.K. Kathiravan, J.B. Bariwal, A.K. Shah, K.S. Jain, Tetrahedron Lett. 49 (2008) 1269–1273. [6] R. Gundla, R. Kazemi, R. Sanam, R. Muttineni, J.A.R.P. Sarma, R. Dayam and N. Neamati, J. Med. Chem. 51 (2008) 3367–3377. [7] J.C. Yarrow, Y. Feng, Z.E. Perlman, T. Kirchhausen, T.J. Mitchison, Comb. Chem. High Throughput Screen 6 (2003) 279–286. [8] Y. Feng, A.P. Jadhav, C. Rodighiero, Y. Fujinaga, T. Kirchhausen and W.I. Lencer EMBO Rep. 5 (2004) 596–601. [9] R.A. Spooner, P. Watson, D.C. Smith, F. Boal, M. Amessou, L. Johannes, G.J. Clarkson, J.M. Lord, D.J. Stephens and L.M. Roberts, Biochem. J. 414 (2008) 471–484. [10] M. Nagaraju, A. Krishnaiah, H.B. Mereyala, Synth.Commun. 35 (2007) 2467–2472. [11] For reviews on the synthesis of pyrimidine triazoles see a) M.A.E. Shaban and A.E.A. Morgaan, Adv. Heterocyclic Chem. 75 (1999) 131–176 b) M.A.E. Shaban and A.E.A. Morgaan, Adv. Heterocyclic Chem. 75 (1999) 243–281. [12] for examples of cyclisation with orthoformates see a) A.E. Rashad, O.A. Heikal, A.O.H. El-Nezhawy, and F.M.E. Abdel-Megeid, Heteroatom. Chem. 16 (2005) 226–234 b) D.J. Brown, T. Nagamatsu, Aust. J. Chem. 31 (1978) 2505–2515. [13] For an example of cyclisation with activated acid derivatives see Y. Wang, K. Sarris, D.R. Sauer, S.W. Djuric, Tetrahedron Letts. 48 (2007) 2237–2240. [14] H. Chen, Z. Shang, J. Chang, Synth. Commun. 36 (2006) 445–450. [15] T. Nagamatsu, H. Yamasaki, T. Akiyama, S. Hara, K. Mori, H. Kusakabe, Synthesis, 4 (1999) 655–663. [16] A.F. Khattab, F.A. El-Essawy, J. Chem. Res. (2005) 736–740. [17] a) R. Kumar, R.R. Nair , S.S. Dhiman , J. Sharma , O. Prakash, Euro. J. Med. Chem. 44 (2000) 2260–2264 b) A.K. Sadana, Y. Mirza, K.R. Aneja, O. Prakash, Euro. J. Med. Chem. 38 (2003) 533–536 c) O. Prakash, V. Bhardwaj, R. Kumar, P. Tyagi, K.R. Aneja, Euro. J. Med. Chem. 39 (2004) 1073–1077 d) O. Prakash, R. Kumar, D. Sharma, R. Naithani, R. Kumar, Heteroatom Chem. 17 (2006) 653–655 e) O. Prakash, R. Kumar , R. Kumar , P. Tyagi , R.C. Kuhad, Euro. J. Med. Chem. 42 (2007) 868–872 f) B.S. Joe, H.Y. Son, Y.-H. Song, Heterocycles 75 (2008) 3091–3097 g) R. Kumar, R.R. Nair, S.S. Dhiman, J. Sharma, O. Prakash, Euro. J. Med. Chem. 44 (2009) 2260–2264. [18] V.J. Ram; H.K. Pandey; A.J. Vlietinck, J. Heterocyclic Chem. 18 (1981) 1277–1280. [19] For the oxidation of sodium iodide by sulfoxides see a) J.H. Krueger, Inorg. Chem. 5 (1966) 132–136. b) G. Modena, G. Scorrano, D. Landini, F. Montanari, Tetrahedron Lett. 28 (1966) 3309–3313. [20] C. Lin, P.-T. Lai, S.K.-S. Liao, W.-T. Hung, W.-B. Yang, J.-M. Fang, J. Org. Chem. 73 (2008) 3848–3853. See also the sulphur catalysed oxidation of aminomethylpyridines to imidazopyridines in F. Shibahara, R. Sugiura, E. Yamaguchi, A. Kitagawa, T. Murai, J. Org. Chem. 74 (2009) 3566–3568. [21] For reviews on the Dimroth rearrangement in triazolopyrimidine systems see a) E.S.H. El Ashry, Y. El Kilany, N. Rashed, Adv. Heterocyclic Chem. 75 (1999) 79–167 b) See reference 11. [22] E.V. Vorob´ev, M.E. Kletskii, V.V. Krasnikov, V.V. Mezheritskii, D.V. Steglenko, Russ. Chem. Bull. Int. Ed. 55 (2006) 2247–2255. [23] For similar cyclisations of amino imines with aldehydes but done in DMF/HOAc see a) N.A. Hassan; M.I. Hegab; A.E. Rashad; A.A. Fahmy; F.M.E. Abdel-Megeid, Nucleos. Nucleot. 26 (2007) 379–390 b) E.K. Ahmed, M.A. Ameen, F.F. Abdel-latif, Phosphorus, Sulfur Silicon Relat. Elem. 181 (2006) 497–510. [24] For examples of the arial oxidation of other diamino heterocycles see a) M. Curini, F. Epifano, F. Montanari, O. Rosati, S.Taccone, Syn. Lett. 10 (2004) 1832–1834. [25] C.J. Shishoo, M B. Devani, G.V. Ullas, S. Ananthan, V.S. Bhadti, J. Heterocyclic Chem. 18 (1981) 43–46. [26] J. Tonnar, P. Lacroix-Desmazes, Angew. Chem. Int. Ed. Engl. 47 (2009) 1294–1297. [27] a) G.M. Sheldrick, SHELXL97. Program for the Refinement of Crystal Structures, University of Göttingen, Göttingen, Germany, 1997 b) G. M. Sheldrick, Acta Cryst. A64 (2008) 112-122.
URI:	http://wrap.warwick.ac.uk/id/eprint/3289

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