Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2014; 46(18): 2436-2444
DOI: 10.1055/s-0033-1338647
DOI: 10.1055/s-0033-1338647
paper
Synthesis of Novel Thymine-β-lactam Hybrids and Evaluation of Their Antitumor Activity
Further Information
Publication History
Received: 07 April 2014
Accepted: 24 April 2014
Publication Date:
01 July 2014 (online)
Abstract
Trimethylene-tethered thymine-β-lactam and thymine-bis-β-lactam chimeras were prepared as novel classes of hybrid systems through selective mono- or bis-N-alkylation of thymine with cis-1-(3-bromopropyl)-β-lactams. In addition, acidic methanolysis of the β-lactam nucleus in these systems provided an entry into the class of thymine-β-amino ester hybrids. A selection of the newly synthesized hybrid compounds was assessed for their antiviral activity, cytotoxicity, and cytostatic activity, revealing a significant cytostatic effect of one of the derivatives against murine leukemia and human T-lymphocyte tumor cells.
Supporting Information
- for this article is available online at http://www.thieme-connect.com/products/ejournals/journal/ 10.1055/s-00000084.
- Supporting Information
-
References
- 1a De Clercq E. J. Clin. Virol. 2004; 30: 115
- 1b Lee VH. L. Eur. J. Pharm. Sci. 2000; 11: S41
- 1c Balzarini J. Pharm. World Sci. 1994; 16: 113
- 2a Decker M. Curr. Med. Chem. 2011; 18: 1464
- 2b Tsogoeva SB. Mini-Rev. Med. Chem. 2010; 10: 773
- 2c Muregi FW, Ishih A. Drug Dev. Res. 2010; 71: 20
- 2d Meunier B. Acc. Chem. Res. 2008; 41: 69
- 3 Vandekerckhove S, D’hooghe M. Bioorg. Med. Chem. 2013; 21: 3643
- 4a Mehta PD, Sengar NP. S, Pathak AK. Eur. J. Med. Chem. 2010; 45: 5541
- 4b Testero SA, Fisher JF, Mobashery S In Burger’s Medicinal Chemistry, Drug Discovery and Development . Vol. 7. Abraham DJ, Rotella DP. John Wiley & Sons; New York: 2010: 257
- 4c Fisher JF, Meroueh SO, Mobashery S. Chem. Rev. 2005; 105: 395
- 4d Burnett DA. Curr. Med. Chem. 2004; 11: 1873
- 5a Ojima I, Zuniga ES, Seitz JD. Top. Heterocycl. Chem. 2013; 30: 1
- 5b Kamath A, Ojima I. Tetrahedron 2012; 68: 10640
- 5c Alcaide B, Almendros P, Aragoncillo C. Chem. Rev. 2007; 107: 4437
- 5d Alcaide B, Almendros P. Curr. Med. Chem. 2004; 11: 1921
- 5e Deshmukh AR. A. S, Bhawal BM, Krishnaswamy D, Govande VV, Shinkre BA, Jayanthi A. Curr. Med. Chem. 2004; 11: 1889
- 5f Palomo C, Aizpurua JM, Ganboa I, Oiarbide M. Curr. Med. Chem. 2004; 11: 1837
- 5g Singh GS. Tetrahedron 2003; 59: 7631
- 5h Alcaide B, Almendros P. Synlett 2002; 381
- 6 Palomo C, Aizpurua JM, Balentova E, Azcune I, Santos JI, Jimenez-Barbero J, Canada J, Miranda JI. Org. Lett. 2008; 10: 2227
- 7a Singh P, Singh P, Kumar M, Gut J, Rosenthal PJ, Kumar K, Kumar V, Mahajan MP, Bisetty K. Bioorg. Med. Chem. Lett. 2012; 22: 57
- 7b Singh P, Raj R, Singh P, Gut J, Rosenthal PJ, Kumar V. Eur. J. Med. Chem. 2014; 71: 128
- 7c Singh P, Sachdeva S, Raj R, Kumar V, Mahajan MP, Nasser S, Vivas L, Gut J, Rosenthal PJ, Feng TS, Chibale K. Bioorg. Med. Chem. Lett. 2011; 21: 4561
- 8a Singh P, Raj R, Kumar V, Mahajan MP, Bedi PM. S, Kaur T, Saxena AK. Eur. J. Med. Chem. 2012; 47: 594
- 9a Raj R, Singh P, Haberkern NT, Faucher RM, Patel N, Land KM, Kumar V. Eur. J. Med. Chem. 2013; 63: 897
- 9b Raj R, Sharma V, Hopper MJ, Patel N, Hall D, Wrischnik LA, Land KM, Kumar V. Med. Chem. Res. 2014; DOI 10.1007/s00044-014-0956-6
- 10 Greene LM, Wang S, O’Boyle NM, Bright SA, Reid JE, Kelly P, Meegan MJ, Zisterer DM. Oncol. Rep. 2013; 29: 2451
- 11 Pori M, Galletti P, Soldati R, Calza L, Mangano C, Giacomini D. Eur. J. Med. Chem. 2013; 70: 857
- 12 Raj R, Biot C, Carrere-Kremer S, Kremer L, Guerardel Y, Gut J, Rosenthal PJ, Kumar V. Chem. Biol. Drug Des. 2014; 83: 191
- 13 D’hooghe M, Mollet K, De Vreese R, Jonckers T, Dams G, De Kimpe N. J. Med. Chem. 2012; 55: 5637
- 14a Dömling A, Starnecker M, Ugi I. Angew. Chem., Int. Ed. Engl. 1995; 34: 2238
- 14b Basak A, Pal R. Bioorg. Med. Chem. Lett. 2005; 15: 2015
- 15a Montgomery JA. Med. Res. Rev. 1982; 2: 271
- 15b Galmarini CM, Mackey JR, Dumontet C. Lancet Oncol. 2002; 3: 415
- 15c De Clercq E. Med. Res. Rev. 2008; 28: 929
- 16 Nawrot B, Michalak O, Olejniczak S, Wieczorek MW, Lis T, Stec WJ. Tetrahedron 2001; 57: 3979
- 17a Dekeukeleire S, D’hooghe M, Vanwalleghem M, Van Brabandt W, De Kimpe N. Tetrahedron 2012; 68: 10827
- 17b D’hooghe M, Dekeukeleire S, De Kimpe N. Org. Biomol. Chem. 2008; 6: 1190
- 17c Van Brabandt W, Vanwalleghem M, D’hooghe M, De Kimpe N. J. Org. Chem. 2006; 71: 7083
- 18a Barrow KD, Spotswood TM. Tetrahedron Lett. 1965; 6: 3325
- 18b Decazes J, Luche JL, Kagan HB. Tetrahedron Lett. 1970; 11: 3361
- 19 Shaw G In Comprehensive Heterocyclic Chemistry II . Vol. 7. Ramsden CA. Elsevier; Oxford: 1996: 397
- 20 Ganguly S, Kundu KK. Can. J. Chem. 1994; 72: 1120
- 21 Nakanishi K, Suzuki N, Yamazaki F. Bull. Chem. Soc. Jpn. 1961; 34: 53
- 22 Wittenburg E. Chem. Ber. 1966; 99: 2391
- 23a Mollet K, D’hooghe M, De Kimpe N. Mini-Rev. Org. Chem. 2013; 10: 1
- 23b D’hooghe M, Dekeukeleire S, Leemans E, De Kimpe N. Pure Appl. Chem. 2010; 82: 1749
- 23c Ojima I, Delaloge F. Chem. Soc. Rev. 1997; 377
- 23d Ojima I. Acc. Chem. Res. 1995; 28: 383
- 24a Mollet K, D’hooghe M, De Kimpe N. Tetrahedron 2012; 68: 10787
- 24b Leemans E, D’hooghe M, Dejaegher Y, Törnroos KW, De Kimpe N. Eur. J. Org. Chem. 2010; 352
- 24c Palomo C, Aizpurua JM, Ganboa I, Oiarbide M. Synlett 2001; 1813