Abstract
The synthesis of new cyclic and acyclic nucleoside analogues
was achieved by alkylation of 5-halogenated 6-(2,4-dichlorophenoxymethyl)pyrimidine-2,4-dione
following the Vorbrüggen coupling procedure. Nucleoside
analogues of the 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine
(HEPT)-type were obtained as well as analogues of ganciclovir, acyclovir,
and ribonucleosides. All compounds were tested against a variety
of viruses. Three of the new compounds were potent and selective
anti-HIV-1 inhibitors.
Key words
bioorganic chemistry - drugs - antiviral agents - nucleosides - glycosylation
References
1 Richman DD.
Fischl MA.
Grieco MH.
Gottieb MS.
Volberding PA.
Lasin OL.
Leedon JM.
Groopman JE.
Mildran D.
Hirsch MS.
Jackson GG.
Durack DT.
Lehrman NS. and the AZT Collaborative Working GroupN. Engl.
J. Med.
1987,
317:
192
2 Yarchoan R.
Mitsuya H.
Thamas RV.
Pluda J.
Hartman NR.
Perno CF.
Marczyck KS.
Allain JP.
Johns DG.
Broder S.
Science
1989,
245:
412
3 Larder BA.
Darby G.
Richman DV.
Science
1989,
243:
1731
4a Roy-Burman P.
Analogues
of Nucleic Acid Components
Springer-Verlag;
New
York:
1970.
4b Goodman L. In Basic Principles in Nucleic Acid Chemistry
Vol.
1:
Ts’V POP.
Academic
Press;
New York:
1974.
p.146
4c Uesugi S.
Ikehara M.
Chem. Pharm. Bull.
1978,
26:
3040
5a Baba M.
De Clercq E.
Tanaka H.
Ubasawa M.
Takashima H.
Sekiya K.
Nitta I.
Umezu K.
Walker RT.
Mori S.
Ito M.
Shigeta S.
Miyasaka T.
Mol. Pharmacol.
1993,
39:
805
5b Pontkis R.
Benhida R.
Aubertin AM.
Grierson DS.
Monneret C.
J.
Med. Chem.
1997,
40:
1845
5c Kim DK.
Gam J.
Kim YW.
Lim J.
Kim HT.
Kim KH.
J. Med. Chem.
1997,
40:
2363
6a Niedballa U.
Vorbrüggen H.
J.
Org. Chem.
1974,
39:
3654
6b Niedballa U.
Vorbrüggen H.
J. Org. Chem.
1976,
41:
2084
6c Vorbrüggen H.
Krolikiewiecz K.
Bennua B.
Chem. Ber.
1981,
114:
1234
7a Andersen GW.
Halverstadt IF.
Miller WH.
Roblin RO.
J. Am. Chem. Soc.
1945,
67:
2197
7b El-telbani EM.
Elshehry MF.
Nawwar GAM.
Monatsh. Chem.
2008,
139:
685
8 Johnson TB.
Ambelang JC.
J. Am. Chem. Soc.
1938,
60:
2941
9 Donleavy JJ.
Kise MA.
Org.
Synth. Coll. Vol. II
Wiley;
New
York:
1943.
p.422 ; Org. Synth. 1937 , 17 , 63
10 Asakura J.-I.
Robins MJ.
J. Org. Chem.
1990,
55:
4928
11 Jourdan F.
Laduree D.
Robba M.
J.
Heterocycl. Chem.
1994,
31:
305
12 All new compounds were evaluated concerning
their ability to inhibit the replication of HIV in T-lymphocytes
cells. Briefly, a CEM cell suspension was infected with HIV-1 or HIV-2.
The mutant thymidine kinase-deficient CEM cell cultures were only
infected with HIV-2. Then, 100 µL of the infected cell
suspensions was transferred into 96-well microtiter plate wells
and mixed with 100 µL of the appropriate dilutions of the
test compounds. After 4-5 days, giant cell formation was
recorded microscopically in the HIV-infected cell cultures.
13 Balzarini J.
Karlsson A.
De Clercq E.
Mol.
Pharmacol.
1993,
44:
694
