Novel 5-(N-Alkylaminouracil)
Acyclic Nucleosides

Sławomir Boncel; Andrzej Gondela; Maciej Mączka; Magdalena Tuszkiewicz-Kuźnik; Przemysław Grec; Barbara Hefczyc; Krzysztof Walczak

doi:10.1055/s-0030-1258397

PAPER

Novel 5-(N-Alkylaminouracil) Acyclic Nucleosides

Sławomir Boncel^a, Andrzej Gondela^a, Maciej Mączka^a, Magdalena Tuszkiewicz-Kuźnik^a, Przemysław Grec^a, Barbara Hefczyc^b, Krzysztof Walczak*^a
^a Silesian University of Technology, Department of Organic Chemistry, Bioorganic Chemistry and Biotechnology, Krzywoustego 4, 44-100 Gliwice, Poland
Fax: +48(32)2372094; e-Mail: Krzysztof.Walczak@polsl.pl;
^b Silesian University of Technology, Department of Chemical Organic Technology and Petrochemistry, Krzywoustego 4, 44-100 Gliwice, Poland

Abstract

All articles of this category

Abstract

Protocols for the two-step syntheses of new 5-(N-hydroxyalkyl- and 5-N-benzylamino)uracil acyclic nucleosides bearing various functional groups (alkoxy/hydroxy and cyano/ester) are presented. Two groups of the title compounds were synthesised via aminolysis of 5-bromouracil and, subsequently, either coupling with an alkylating agent (2-chloromethoxyethyl acetate), or Michael-type addition to acrylonitrile/methyl acrylate. The reverse sequences for both syntheses were also studied. The target molecules were designed as non-nucleoside reverse transcriptase inhibitors (NNRTI) and are analogues of 1-(hydroxyethoxymethyl)-6-thiophenylthymine (HEPT) and 3-benzyl-1-cyanomethyluracils. The obtained compounds will be used in screening tests for anti-HIV-1 activity.

Key words

acyclic nucleosides - 5-(N-alkylamino)uracil - aminolysis - N-alkylation - Michael-type addition

Full Text

References

1 Gumina G. Choi Y. Chu CK. Antiviral Nucleosides - Chiral Synthesis and Chemotherapy Elsevier; Amsterdam: 2003. p.46

2 Miyasaka T. Tanaka H. Baba M. Hayakawa H. Walker RT. Balzarini J. De Clercq E. J. Med. Chem. 1989, 32: 2507

3 De Clercq E. Field HJ. Br. J. Pharmacol. 2006, 147: 1

4 Faulds D. Heel RC. Drugs 1990, 39: 597

5 Baraldi PG. Romagnoli R. Guadix AE. Pineda de las Infantas MJP. Gallo MA. Espinosa A. Martinez A. Bingham JP. Hartley JA. J. Med. Chem. 2002, 45: 3630

6 Ozarov AA. Novikov MS. Chem. Heterocycl. Compd. 2005, 41: 766

7 Ozarov AA. Novikov MS. Brel’ AK. Solodunova GN. Chem. Heterocycl. Compd. 1998, 34: 611

8 Zemlicka J. In Nucleosides and Nucleotides as Antitumor and Antiviral Agents Chu CK. Baker DC. Plenum Press; New York: 1993.

9 Maruyama T. Kozai S. Demizu Y. Witvurow M. Pannecouque C. Balzarini J. Snoecks R. Andrei G. De Clercq E. Chem. Pharm. Bull. 2006, 54: 325

10 Philips AP. J. Am. Chem. Soc. 1951, 73: 1061

11 Gerns FR. Perrota A. Hitchings GH. J. Med. Chem. 1966, 9: 108

12 Majmudar KC. Das U. Jana NK. J. Org. Chem. 1998, 63: 3550

13 Fang W.-P. Cheng Y.-T. Cheng Y.-R. Czerng Y.-J. Tetrahedron 2005, 61: 3107

14 Senda S. Hirota K. Banno K. J. Med. Chem. 1972, 15: 471

15 Vorbrüggen H. Ruh-Pohlenz C. Org. React. 2000, 55: 1

16 Boncel S. Gondela A. Walczak K. Synthesis 2010, 1573

17 Boncel S. Mączka M. Walczak KZ. Tetrahedron 2010, 66: 8450

18 Foye WO. Kauffman JM. Kim YH. J. Heterocycl. Chem. 1982, 19: 497

19 Bobkov GV. Brilliantov KV. Mikhailov SN. Rozenski J. Aerschot AV. Herdewijn P. Collect. Czech. Chem. Commun. 2006, 71: 804

20 Senkus M. J. Am. Chem. Soc. 1946, 68: 734

21 Rosowsky A. Kim S.-H. Wick M. J. Med. Chem. 1981, 24: 1177