Synthesis of l-(alkoxymethyl)-5-benzyl-6-methyluracil as potential nonnucleoside HIV-1 RT inhibitors

Synthetic Communications

Volumn 36, Issue 19, 2006, Pages 2913-2920

  Chen, Yanli ^a   Guo, Ying ^a   Yang, Hua ^a   Wang, Xiaowei ^a   Liu, Junyi ^a  

^a PEKING UNIVERSITY   (China)

Author keywords

HIV 1 reverse transcriptase; N 1 alkylated 5 benzyl 6 methyluracil; Nonnucleoside reverse transcriptase inhibitors

Indexed keywords

1 (ALKOXYMETHYL) 5 BENZYL 6 METHYLURACIL; 1 (BENZYLOXYMETHYL) 5 BENZYL 6 METHYLURACIL; 1 (ETHOXYMETHYL) 5 BENZYL 6 METHYLURACIL; 1,3 DIBENZYL 5 BROMOMETHYL 6 METHYLURACIL; 1,3 DIBENZYL 6 METHYL 5 ZINCBROMOMETHYLURACIL; 1,3,5 TRIBENZYL 6 METHYLURACIL; 5 BENZYL 6 METHYLURACIL; 6 METHYLURACIL; BENZYL DERIVATIVE; BENZYLIC ZINC; BIS(DIBENZYLIDENEACETONE)PALLADIUM; CHLOROMETHYL BENZYL ETHER; CHLOROMETHYL ETHYL ETHER; ETHER DERIVATIVE; IODINE DERIVATIVE; PALLADIUM COMPLEX; PHOSPHORUS DERIVATIVE; REAGENT; RNA DIRECTED DNA POLYMERASE; RNA DIRECTED DNA POLYMERASE INHIBITOR; THYMINE DERIVATIVE; UNCLASSIFIED DRUG; ZINC DERIVATIVE;

ALKYLATION; ANTIVIRAL ACTIVITY; ARTICLE; CATALYST; CROSS COUPLING REACTION; DEALKYLATION; DRUG SYNTHESIS; ENZYME INHIBITION; HUMAN IMMUNODEFICIENCY VIRUS 1;

EID: 33750088984     PISSN: 00397911     EISSN: 15322432     Source Type: Journal    
DOI: 10.1080/00397910600772850     Document Type: Article

References (16)

1. Barre-Sinoussi, F.; Chermann, J. C.; Rey, F.; Chamaret, M. T.; Grust, J.; Daugnet, C.; Axler-Belin, C.; Vezinet-Brun, F.; Rouziout, C.; Rozenhaum, W.; Montagnier, L. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 1983, 220, 868-871.
2. Gallo, R. C.; Salahnddin, S. Z.; Popovic, M.; Shearer, G. M.; Kaplan, M.; Haynes, B. F.; Palker, T. J.; Redifield, R.; Oleske, J.; Safai, B.; White, G.; Foster, P.; Markham, P. O. Frequent detection and isolation of cytopathic retrovirus (HTLV-III) from patients with AIDS at a risk for AIDS. Science 1984, 224, 500-503.
3. Mitsuya, H.; Weinhold, K. J.; Furman, P. A.; St. Clair, H. M.; Lehrman, S. N.; Gallo, R. C.; Bolognesi, D.; Barry, D. W.; Broder, S. 3′-Azido-3′-deoxythymidine (BW A509U): An antiviral agent that inhibits the infectivity and cytopathic effect of human T-lymphotropic virus type III/lymphadenopathy-associated virus in vitro. Proc. Natl. Acad. Sci. USA 1985, 82, 7096-7100.
4. Jacobo-Molina, A.; Ding, J.; Nanni, R. G.; Clarq, A. D.; Lu, X.; Tantillo, C.; Waillams, R. L.; Kramer, G.; Ferris, A. L.; Clarck, P.; Hizi, A.; Hughes, S. H. Arnold, E. Crystal structure of human immunodeficiency virus type 1 reverse transcriptase complexed with double-stranded DNA at 3.0 Å resolution shows bent DNA. Proc. Natl. Acad. Sci. USA 1994, 90, 6320-6324.
5. Tadashi, M.; Hiromichi, T.; Masanor, B.; Hiroyuki, H.; Richard, T.; Balzarini, J.; Declercq, E. A novel lead for specific anti-HIV-1 agents: 1-[(2-Hydroxyethoxy)-methyl]-6-(phenylthio)thymine. J. Med. Chem. 1989, 32, 2507-2509.
6. El-Brollosy, N. R.; Jorgensen, P. T.; Dahan, B.; Boel, A. M.; Pedersen, E. B.; Nielsen, C. Synthesis of novel N-1 (allyloxymethyl) analogues of 6-benzyl-1-(ethoxymethyl)-5-isopropyluracil (MKC-442, emivirine) with improved activity against HIV-1 and its mutants. J. Med. Chem. 2005, 45 (26), 5721-5726.
7. Richard, E. C.; Robert, M. F.; Kay, F. Synthesis of 5-substituted pyrimidines via, formaldehyde addition. J. Am. Chem. Soc. 1959, 81 (10), 2521-2527.
8. Kenochel, P.; Almena Perea, J. J.; Jones, P. Organozinc mediated reactions. Tetrahedron 1998, 54, 8275-8319.
9. Farina, V.; Kapadia, S.; Krishnan, B.; Wang, C.; Liebes Kind, L. S. On the nature of the "copper effect" in the Stille cross-coupling. J. Org. Chem. 1991, 59, 5905-5911.
10. Lohse, O.; Beutler, U.; Funfschilling, P.; Furet, P.; France, J.; Kaufmann, D.; Penn, G.; Zaugg, W. New synthesis of oxcarbazepine via remote metalation of protected N-o-tolyl-anthranilamide derivatives. Tetrahedron. Lett. 2001, 42, 385-389.
11. Yocla, H.; Nakajima, T.; Takabe, K. Synlett 1991, 911.
12. Renard, A.; Kotera, M.; Lhomme, J. A new short synthesis of deoxyhydantocidin derivatives. Tetrahedron Lett. 1998, 39, 3129-3132.
13. Fuhke, C.; Es-Sayed, M.; Demeijere, A. Org. Lett. 2000, 2, 4249.
14. Zimmerman, M. N.; Nemeroff, N. H.; Book, C. W.; Bhat, K. L. An expeditious synthesis of pyppolo[3, 4-dl]-pyrimidine-2,4-dione from uracil. Heterocyles 2000, 53, 205-211.
15. Tucker, T. J.; Lyle, T. A.; Wiscount, C. M.; Britcher, S. F.; Young, S. D.; Sanders, W. M.; Lumma, W. C.; Goldman, M. E.; O'Brien, J. A. Synthesis of a series of 4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H)- ones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors. J. Med. Chem. 1994, 37, 2437-2444.
16. Richard, E. C.; Robert, M. F.; Kay, F. Synthesis of 5-substituted- pyrimidines via formaldehyde, addition. J. Am. Chem. Soc. 1959, 81, 2521-2527.