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The following 5-(2-substituted vinyl)-6-aza-2'-deoxyuridines were synthesized: (E)-5-(2-bromovinyl) (2) (6-aza-BVDU), 5-(2-bromo-2-fluorovinyl) (a mixture of E and Z isomers) (3), (E)-5-(2-chlorovinyl) (4), (E)-5-[2-(methylthio)vinyl] (5), 5-(2,2-dibromovinyl) (6), and 5-(3-furyl) (7). The synthesis of 2-6 utilized Wittig-type reactions on 5-formyl-1-(2'-deoxy-3', 5'-di-O-p-toluoyl-beta-D-erythro-pentofuranosyl)-6-azauracil (16). 6-Aza-BVDU (and its alpha-anomer) was also synthesized from (E)-5-(2-bromovinyl)-6-azauracil (12) by using standard deoxyribosidation methodology. Compound 7 was prepared from 5-(3-furyl)-6-azauracil (33) via a ribosidation/deoxygenation sequence. An attempt to prepare the corresponding 5-(2,2-difluorovinyl) analogue afforded instead a mixture of the 5-[(2,2-difluoro-2-methoxy)ethyl] and 5-(2,2,2-trifluoroethyl) derivatives 29 and 30. Compounds 2-7, 29, and 30 were tested for in vitro activity against herpes simplex virus types 1 and 2 (HSV-1, HSV-2). 6-Aza-BVDU (2) exhibited ID50s of 8 micrograms/mL vs. HSV-1 and 190 micrograms/mL vs. HSV-2. BVDU (1) had ID50s of 0.015 and 1.6 micrograms/mL against HSV-1 and HSV-2, respectively. Compound 4 showed a similar profile of activity, but the other analogues were either weakly active or inactive.
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
June 1991,
Journal of medicinal chemistry,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
July 1976,
Journal of medicinal chemistry,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
January 1979,
Voprosy virusologii,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
October 1980,
Methods and findings in experimental and clinical pharmacology,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
September 1988,
Journal of medicinal chemistry,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
January 1985,
Nucleic acids symposium series,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
November 1979,
Biochemical pharmacology,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
July 2012,
European journal of medicinal chemistry,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
September 1985,
Bioorganicheskaia khimiia,
W L Mitchell, and
P Ravenscroft, and
M L Hill, and
L J Knutsen, and
B D Judkins, and
R F Newton, and
D I Scopes
July 1987,
Bioorganicheskaia khimiia,
