A new synthesis and an antiviral assessment of the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin

Article abstract of DOI:10.1016/j.bmc.2009.03.004

A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the 4′-fluoro derivative of 4′-deoxy-5′-noraristeromycin, 3) is described via a fluorinated cyclopentanol, which is in contrast to existing schemes where

Full text of DOI:10.1016/j.bmc.2009.03.004

Bioorganic & Medicinal Chemistry 17 (2009) 3126–3129
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Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
A new synthesis and an antiviral assessment of the 40-fluoro derivative
of 40-deoxy-50-noraristeromycin
*
Xue-qiang Yin, Wei-kuan Li, Minmin Yang, Stewart W. Schneller
Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
A synthetic route to (1S,2S,3R,5S)-3-(6-amino-9H-purin-9-yl)-5-fluorocyclopentane-1,2-diol (that is, the
40-fluoro derivative of 40-deoxy-50-noraristeromycin, 3) is described via a fluorinated cyclopentanol,
which is in contrast to existing schemes where fluorination occurred once the purine ring was present.
Compound 3 was assayed versus a number of viruses. A favorable response was observed towards mea-
Received 8 January 2009
Revised 2 March 2009
Accepted 3 March 2009
Available online 9 March 2009
sles (IC50 of 1.2
l
g/mL in the neutral red assay and 14
l
g/mL by the visual assay) but this was accompa-
nied by cytotoxicity in the CV-1 host cells (21–36
l
g/mL). Among the viruses unaffected by 3 were
Keywords:
Enantiospecific
Adenine
Carbocyclic nucleosides
Antiviral
human cytomegalovirus and the poxviruses (vaccinia and cowpox), which are three viruses that were
inhibited by the 40,40-difluoro analog of 3 (that is, 2).
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
followed by amination yielded 13. Subsequent, acidic deisopropyli-
denation resulted in 3.
To build upon the framework of the antiviral agent 50-norariste-
The structure of 3 was confirmed by NMR analysis (ge-NOESY,
ge-COSY, and ge-HMBC): (1) for the fluoro stereochemistry at the
C-40 center (Fig. 1), there was a strong NOE between H-40 and H-
romycin (1) (Fig. 1)1 we recently reported2 the effects of the di-
fluoro congener
2 towards human cytomegalovirus and the
orthopox viruses vaccinia and cowpox. To ascertain if these latter
activities also reside in the monofluoro analog 3, a new synthesis
of it3,4 was developed and an antiviral analysis conducted.
10 and H-50 ( ) and between H-20 and H0-50 (b) and (2) for the N-
a
9 cyclopentyl substitution site, HMBC assessment found a three-
bond coupling between H-10 and purine C-4 (150.2) and C-8
(140.2).
2. Chemistry
3. Antiviral results
The previous routes to 33,4 introduced the fluoro substituent
onto a preformed carbocyclic nucleoside precursor. In the present
case, it was desired to have access to a fluorinated cyclopentanol
that would lend itself to condensation with a variety of heterocy-
clic bases, including adenine or its precursors. Thus, for this pur-
pose, 12 (Scheme 1) became the initial target compound.
Compound 3 was subjected to broad antiviral analysis.10,11
favorable response was observed towards measles (IC50 of 1.2
mL in the neutral red assay and 14
but this was accompanied by cytotoxicity in the CV-1 host cells
(21–36 g/mL). Among the viruses unaffected by 3 were human
A
g/
l
l
g/mL by the visual assay)
l
To begin, the protected ketone 5,5 available from (+)-(1R,4S)-4-
cytomegalovirus and the poxviruses (vaccinia and cowpox), which
are three viruses inhibited by the difluoro analog of 3 (that is, 2).2
hydroxy-2-cyclopenten-1-yl acetate, 46), which is
a common
building block in our carbocyclic nucleoside research,2 was re-
duced (Luche conditions)7 to 6. This was followed by a p-methoxy-
benzyl protection (to 7) and then a desilylation to 8. Oxidation of 8
(Parikh–Doering procedure)8 produced 9. Reduction of 9 to 10 with
subsequent fluorination (11) and deprotection provided the sought
12. Subjecting 12 to Mitsunobu conditions9 with 6-chloropurine
4. Conclusion
The synthetic route described herein offers advantages over the
two previously described linear routes3,4 by (i) following a conver-
gent pathway that lends itself to compound library development
with various heterocyclic bases and (ii) by introducing the requi-
site fluorine atom at a stage where its stereochemistry is assured
(prior to any influence by the purine base). These results are signif-
icant as structural variations of 3 are pursued to explore its poten-
tial in the treatment of measles without associated cytotoxicity.
* Corresponding author. Tel.: +1 334 844 5737; fax: +1 334 844 5748.
E-mail address: schnest@auburn.edu (S.W. Schneller).
0968-0896/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2009.03.004

X. Yin et al. / Bioorg. Med. Chem. 17 (2009) 3126–3129
3127
bined organic layers were dried (Na2SO4) and concentrated. The
residue was purified by silica gel column chromatography
(EtOAc/hexanes, 3:1) to give 6 as a colorless oil (0.34 g, 97%): 1H
NMR (400 MHz, CDCl3) d 4.56 (t, J = 5.44 Hz, 1H), 4.34–4.26 (m,
2H), 4.01 (dd, J = 3.58 Hz, J = 0.46 Hz, 1H), 2.25 (d, J = 10.44 Hz,
1H), 1.89–1.93 (m, 1H), 1.68–1.75 (m, 1H), 1.46 (s, 3H), 1.34 (s,
3H), 0.86 (s, 9H), 0.05 (s, 6H); 13C NMR (100 MHz, CDCl3) d
111.34, 85.83, 78.61, 73.46, 72.00, 39.35, 26.19, 25.91, 24.43,
18.17, ꢂ4.69, ꢂ4.76. Anal. Calcd for C14H28O4Si: C, 58.29; H, 9.78.
Found: C, 58.34; H, 9.85.
5. Experimental
5.1. General remarks
Melting points were recorded on a Meltemp II melting point
apparatus and are uncorrected. Atlantic Microlab, Inc., Norcross,
GA performed the combustion analyses. The NMR spectra were
recorded on Bruker AC 250 and Avance spectrometers and are ref-
erenced to internal tetramethylsilane (TMS) at 0.0 ppm. The spin
multiplicities are indicated by the symbols s (singlet), d (doublet),
t (triplet), m (multiplet), and br (broad). Reactions were monitored
by thin-layer chromatography (TLC) using 0.5-mm Whatman
Diamond Silica Gel 60-F254 precoated plates with visualization by
irradiation with a Mineralight UVGL-25 lamp. Yields refer to chro-
matographically and spectroscopically (1H and 13C NMR) homoge-
neous materials.
5.1.2. tert-Butyl((3aS,4S,6S,6aS)-6-(4-methoxybenzyloxy)-2,2-
dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yloxy)-
dimethylsilane (7)
Compound 6 (7.56 g, 26.2 mmol) was dissolved in dry DMF
(100 mL). After cooling the solution to 0 °C, NaH (1.26 g, 60% in
mineral oil, 31.4 mmol) was added portionwise. The solution was
stirred at 0 °C for 30 min and then 4-methoxybenzyl chloride
(4.3 mL, 31.4 mmol) was added in one portion. After warming
the solution to rt, it was stirred for 3 h. The solvent was removed
under reduced pressure and the residue quenched with H2O fol-
lowed by extraction with EtOAc (3 ꢁ 100 mL). The organic layers
were combined, dried (Na2SO4), concentrated under reduced pres-
sure and the residue subjected to silica gel column chromatogra-
phy (EtOAc/hexanes, 1:10) to give 7 as a colorless oil (9.0 g, 84%):
1H NMR (400 MHz, CDCl3) d 7.29 (d, J = 8.4 Hz, 2H), 6.87 (d,
J = 8.4 Hz, 2H), 4.61 (m, 1H), 4.45–4.58 (m, 2H), 4.25 (dd,
J = 5.6 Hz, J = 1.6 Hz, 1H), 4.02–4.05 (m, 1H), 3.94 (d, J = 4.0 Hz,
1H), 3.79 (s, 3H), 1.90–1.94 (m, 1H), 1.75–1.76 (m, 1H), 1.48 (s,
3H), 1.30 (s, 3H), 0.83 (s, 9H), 0.03 (s, 3H), 0.01 (s, 3H); 13C NMR
5.1.1. (3aS,4S,6S,6aS)-2,2-Dimethyl-6-(tert-butyldimethylsilyl)-
tetrahydro-3aH-cyclopenta[d][1,3]-4-ol (6)
To a solution of 55 (0.35 g, 1.22 mmol) in MeOH (10 mL) was
added CeCl3ꢀ7H2O (0.45 g, 1.22 mmol). This mixture was cooled
to 0 °C and then NaBH4 (60 mg, 1.58 mmol) was added portion-
wise. The resultant mixture was stirred for 30 min at 0 °C, then
warmed to rt followed by stirring for 1 h. The reaction was
quenched with satd NH4Cl solution (5 mL). The solvent was re-
moved under reduce pressure and the residue poured into H2O
with subsequent extraction using EtOAc (3 ꢁ 10 mL). The com-
NH2
(100 MHz, CDCl3),
d 159.24, 130.47, 129.72, 113.72, 110.98,
85.74, 77.76, 77.50, 73.42, 71.55, 55.29, 35.73, 26.13, 25.71,
24.07, 17.93, ꢂ4.89. Anal. Calcd for C22H36O5Si: C, 64.67; H, 8.88.
Found: C, 64.99; H, 8.64.
N
N
X
Y
N
N
1'
4'
5.1.3. (3aR,4S,6S,6aS)-6-(4-Methoxybenzyloxy)-2,2-dimethyl-
tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (8)
OH
HO
To 7 (9.0 g, 22.0 mmol) dissolved in THF (100 mL) was added
tetrabutylammonium fluoride (33 mL, 1.0 M in THF, 33 mmol).
This mixture was stirred at rt for 1 h and then quenched with
H2O. Following extraction with EtOAc (3 ꢁ 300 mL), the combined
organic layers were dried (Na2SO4), concentrated under reduced
1, X=OH;Y=H
2, X=Y=F
3, X=F;Y=H
Figure 1.
NH2
X
Y
N
N
R'O
N
O
h on 12
d
on 8
e
OR
OR
OPMB
N
F
O
O
O
O
O
O
i
10, X=H;Y=OH;R=PMB
11, X=F;Y=H;R=PMB
12, X=F;Y=R=H
6, R=H;R'=TBDMS
7, R=PMB;R'=TBDMS
8, R=PMB;R'=H
9
f
O
b
c
O
3
g
a
13
TBDMSO
OAc
HO
O
ref. 5
4 steps
O
46
O
5
Scheme 1. Reagents and conditions: (a) CeCl3ꢀ7H2O, NaBH4, MeOH, 0 °C to rt, 97%; (b) NaH, PMBCl, DMF, 0 °C, 84%; (c) TBAF, THF, rt, 89%; (d) pyridineꢀSO3, DMSO, DIEPA,
CH2Cl2, 0 °C, 82%; (e) LiAlH4, THF, 0 °C, 81%; (f) DAST, pyridine, CH2Cl2, 0 °C to rt, 70%; (g) DDQ, CH2Cl2/H2O, rt, 86%; (h) (i) TPP, 6-chloropurine, DIAD, THF, 0 °C to rt, 30% (by
proton NMR); (ii) NH3/MeOH, 120 °C, 85%; (i) 0.5 M HCl/MeOH, rt, 93%.

3128
X. Yin et al. / Bioorg. Med. Chem. 17 (2009) 3126–3129
pressure, and subjected to silica gel column chromatography
(EtOAc/hexanes, 1:5–1:1) to give 8 as a colorless oil (5.8 g, 89%):
1H NMR (400 MHz, CDCl3) d 7.31 (d, J = 8.8 Hz, 2H), 6.87 (d,
J = 8.8 Hz, 2H), 4.52–4.66 (m, 3H), 4.32 (dd, J1 = 5.6 Hz, J2 = 1.2 Hz,
1H), 4.04–4.09 (m, 2H), 3.80 (s, 3H), 2.00–2.07(m, 1H), 1.83–1.88
(m, 1H), 1.58 (s, 3H), 1.32 (s, 3H); 13C NMR (100 MHz, CDCl3) d
171.42, 159.46, 130.59, 129.76, 113.98, 111.38, 85.51, 77.96,
73.46, 71.74, 55.48, 35.82, 26.36, 24.29. Anal. Calcd for C16H22O5:
C, 65.29; H, 7.53. Found: C, 65.03; H, 7.62.
5.1.7. 9-((3aS,4R,6S,6aS)-6-Fluoro-2,2-dimethyltetrahydro-3aH-
cyclopenta[d][1,3]dioxol-4-yl)-9H-purin-6-amine (13)
Compound 11 (0.98 g, 3.31 mol) was dissolved in CH2Cl2/H2O
mixture (100 mol CH2Cl2, 5 mol H2O). To this DDQ (0.9 g,
3.96 mol) was added. The resultant mixture was stirred at rt for
1 h. Saturated NaHCO3 (20 mol) was added to quench the reaction.
The organic layer was separated, washed with brine, dried
(Na2SO4), concentrated under reduced pressure, and subjected to
silica gel column chromatography (EtOAc/hexanes, 1:5) to give
(3aS,4S,6S,6aS)-6-fluoro-2,2-dimethyltetrahydro-3aH-cyclopenta[d]-
[1,3]dioxol-4-ol (12) as a white solid (0.5 g, 86%), mp 51–52 °C: 1H
NMR (400 MHz, CDCl3/D2O) d 4.68 (dd, J = 46.0 Hz, J = 3.6 Hz, 1H),
4.56–4.60 (m, 2H), 4.26–4.32 (m, 1H), 2.26–2.32 (td, J = 15.2 Hz,
J = 5.6 Hz, 1H), 1.83 (dddd, J = 44.4 Hz, J = 14.4 Hz, J = 10.8 Hz,
J = 3.6 Hz, 1H), 1.47 (s, 3H), 1.35 (s, 3H); 13C NMR (100 MHz, CDCl3)
d 111.73, 93.81 (d, J = 172.3 Hz), 82.48 (d, J = 33.2 Hz), 78.21, 71.43,
36.89 (d, J = 20.8 Hz), 25.93, 24.14.
After dissolving 12 (0.73 g, 4.14 mol) in dry THF (50 mol), TPP
(1.30 g, 4.9 mol) and 6-chloropurine (0.76 g, 4.9 mol) were added.
This mixture was cooled to 0 °C and then allowed to warm to rt fol-
lowed by heating and stirring at 50 °C overnight. The solvent was
removed under reduced pressure and the residue purified by silica
gel column chromatography to give 6-chloro-9-[(3aS,4R,6S,6aS)-6-
fluoro-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl]-
9H-purine (0.4 g, 30%, estimated from 1H NMR) that was contami-
nated with diisopropyl hydrazine-1,2-dicarboxylate.
In a high pressure reaction vessel, the crude material from the
previous step (0.5 g, 1.6 mmol) was dissolved in dry MeOH
(100 mL). This solution was cooled to 0 °C and saturated with
NH3. The vessel was sealed and heated to 120 °C overnight. The sol-
vent was removed under reduced pressure, and the residue puri-
fied by silica gel column chromatography to give 13 as white
solid (0.4 g, 85%), mp 158–160 °C: 1H NMR (400 MHz, DMSO) d
8.16 (s, 1H), 8.10 (s, 1H), 7.25 (br s, 2H), 4.8–5.2 (m, 4H), 2.55–
2.80 (m, 2H), 1.45 (s, 3H), 1.28 (s, 3H); 13C NMR (62.8 MHz, DMSO)
d 156.01, 152.45, 149.43, 139.10 (d, J = 6.5 Hz), 118.81, 111.44,
96.96 (d, J = 177.6 Hz), 83.52 (d, J = 23.1 Hz), 83.22, 58.65, 35.14
(d, J = 20.3 Hz), 26.26, 24.18. Anal. Calcd for C13H16FN5O2: C,
53.24; H, 5.50; N, 23.88. Found: C, 53.05; H, 5.47; N, 23.74.
5.1.4. (3aS,6S,6aS)-6-(4-Methoxybenzyloxy)-2,2-dimethyl-
dihydro-3aH-cyclopenta[d][1,3]dioxol-4(5H)-one (9)
Compound 8 (5.8 g, 19.7 mmol) was dissolved in dry CH2Cl2
(200 mL) and then DMSO (10 mL) and DIPEA (6.95 mL, 39.4 mmol)
were added. The solution was cooled to 0 °C and PyꢀSO3 complex
(6.25 g, 39.4 mmol) was added portionwise. The solution was stir-
red at 0 °C for 1 h. This mixture was quenched with ice cold H2O
(200 mL). The organic layer was separated, washed with saturated
NaHCO3 and brine, dried (Na2SO4), and concentrated under re-
duced pressure. The residue was purified by silica gel column chro-
matography (EtOAc/hexanes, 1:5–1:1) to give 9 as a colorless oil
(4.7 g, 82%): 1H NMR (400 MHz, CDCl3) d 7.31 (d, J = 8.8 Hz, 2H),
6.89 (d, J = 8.8 Hz, 2H), 4.80 (t, J = 4.2 Hz, 1H), 4.60–4.68 (m, 2H),
4.18 (dt, J = 4.8 Hz, J = 1.2 Hz, 1H), 4.05–4.11 (m, 1H), 3.81 (s, 3H),
2.68–2.76 (m, 1H), 2.47–2.53 (m, 1H), 1.48 (s, 3H), 1.38 (s, 3H);
13C NMR (100 MHz, CDCl3) d 211.05, 159.62, 129.77, 129.25,
113.99, 113.52, 80.51, 77.69, 71.45, 70.08, 55.31, 39.88, 26.90,
25.24. Anal. Calcd for C16H20O5: C, 65.74; H, 6.90. Found: C,
65.60; H, 6.91.
5.1.5. (3aR,4R,6S,6aS)-6-(4-Methoxybenzyloxy)-2,2-dimethyl-
tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (10)
Following dissolving 9 (0.27 g, 0.92 mmol) in dry THF (20 mL),
LiAlH4 (52.3 mg, 1.38 mmol) was added portionwise at 0 °C. The
mixture was then stirred at 0 °C for 3 h and then quenched with
H2O with subsequent filtering through Celite. The filtrate was ex-
tracted with EtOAc (3 ꢁ 50 mL). The combined organic layers were
dried (Na2SO4), and concentrated under reduced pressure to give
10 as a colorless oil (0.22 g, 81%): 1H NMR (400 MHz, CDCl3) d
7.28 (d, J = 8.8 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.52–4.59 (m, 3H),
4.40 (t, J = 5.6 Hz, 1H), 3.80 (s, 3H), 3.69–3.78 (m, 1H), 3.45–3.51
(m, 1H), 2.41 (d, J = 10.8 Hz, 1H), 2.10–2.15 (m, 1H), 1.72–1.80
(m, 1H), 1.56 (s, 3H), 1.37 (s, 3H); 13C NMR (100 MHz, CDCl3) d
159.54, 130.19, 129.73, 114.01, 111.53, 78.48, 78.06, 73.76, 71.36,
68.58, 55.47, 34.76, 25.97, 24.42. Anal. Calcd for C16H22O5: C,
65.29; H, 7.53. Found: C, 65.13; H, 7.53.
5.1.8. (1S,2S,3R,5S)-3-(6-Amino-9H-purin-9-yl)-5-fluorocyclopen-
tane-1,2-diol (3)
Compound 13 (0.4 g, 1.36 mol) was dissolved in 0.5 M Hal in
Mesh (100 mol). The mixture was stirred at rat overnight. The resul-
tant mixture was neutralized with Ambulate IRA-67 ion exchange
resin and then filtered, concentrated under reduced pressure to a
residue that was purified by silica gel column chromatography
(EtOAc/MeOH/NH3–H2O = 3:1:0.2) to give
3 as a white solid
(0.32 g, 93%) mp 256–257 °C (dec.): 1H NMR (250 MHz, DMSO) d
8.16 (s, 1H), 8.12 (s, 1H), 7.22 (s, 2H), 5.36 (d, J = 4.2 Hz, 1H), 5.25
(d, J = 6.5 Hz, 1H), 4.59–4.97 (m, 2H), 4.58–4.63 (m, 1H), 4.04 (dm,
J = 12 Hz, 1H), 2.68–2.76 (m, 1H), 2.20–2.34 (m, 1H); 13C NMR
(62.8 MHz, DMSO) d 156.05, 152.20, 149.69, 140.27, 119.40, 95.14
(d, J = 177.7 Hz), 73.78 (d, J = 10.5 Hz), 73.46, 57.86 (d, J = 3.1 Hz),
33.31 (d, J = 22.6 Hz). Anal. Calcd for C10H12FN5O2: C, 47.43; H,
4.78; N, 27.66. Found: C, 47.28; H, 4.86; N, 27.36.
5.1.6. (3aS,4S,6S,6aS)-6-Fluoro-4-(4-methoxybenzyloxy)-2,2-
dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxole (11)
At 0 °C, pyridine (2.5 mL, 31.2 mmol) was added to 10 (4.7 g,
15.9 mmol) that had been dissolved in dry CH2Cl2 (100 mL).
Retaining the reaction temperature at 0 °C, to this DAST (4.1 mL,
31.2 mmol) was added by means of a syringe. The mixture was
warmed to rt, then refluxed for 2 days under N2. The mixture
was quenched with saturated NaHCO3 solution (100 mol) and the
organic layer separated, dried (Na2SO4), concentrated under re-
duced pressure, and subjected to silica gel column chromatography
(EtOAc/hexanes, 1:5) to give 11 as a colorless oil (3.3 g, 70%): 1H
NMR (400 MHz, CDCl3) d 7.3 (d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz,
2H), 4.47–4.81 (m, 5H), 4.00–4.05 (m, 1H), 3.81 (s, 3H), 2.04–2.14
(m, 2H), 1.48 (s, 3H), 1.32 (s, 3H); 13C NMR (100 MHz, CDCl3) d
159.60, 130.21, 129.81, 114.16, 111.88, 94.40 (d, J = 174.5 Hz),
82.82(d, J = 33.4 Hz), 77.83, 77.13, 71.90, 55.50, 33.70 (d,
J = 20.1 Hz), 26.33, 24.27. Anal. Calcd for C16H21FO4: C, 64.85; H,
7.14. Found: C, 64.72; H, 7.19.
5.2. Antiviral assays
The viruses evaluated and the procedures used are in Refs.
10,11.
Acknowledgments
This research was supported by funds from the Department of
Health and Human Services (AI 56540) (SWS), which is appreciated.

X. Yin et al. / Bioorg. Med. Chem. 17 (2009) 3126–3129
5. Yin, X.-q.; Schneller, S. W. Tetrahedron Lett. 2006, 47, 4057.
3129
We would also like to thank Dr. Earl Kern, University of Alabama-Bir-
mingham; Dr. Erik De Clercq, Rega Institute, Leuven Belgium; Dr.
Brent Korba, Georgetown University, Washington, DC; and, Dr.
Don See, Utah State University, Logan, UT for the antiviral testing.
6. Siddiqi, S. M.; Chen, X.; Schneller, S. W. Nucleosides Nucleotides 1993, 12, 267.
7. Luche, J. L. J. Am. Chem. Soc. 1978, 100, 2226.
8. Parikh, J. R.; Doering, W. J. Am. Chem. Soc. 1967, 89, 5505.
9. (a) Mitsunobu, O. Synthesis 1981, 1; (b) Hughes, D. L. Org. Prep. Proced. Int. 1996,
28, 127; (c) Yin, X.-q.; Li, W.-k.; Schneller, S. W. Tetrahedron Lett. 2006, 47, 9187.
10. Viruses subjected to 3 were herpes simplex virus 1 and 2, herpes simplex virus
1 (TKꢂ), human cytomegalovirus, vaccinia virus, cowpox virus, respiratory
syncytial virus, Punta Toro virus, hepatitis C, coxsackie B4, vesicular stomatitis,
parainfluenza-3, reovirus-1, and Sindbis, measles, influenza A (H1N1, H3N2)
influenza B, feline corona, rhinovirus, and adenovirus.11
References and notes
1. Roy, A.; Serbessa, T.; Schneller, S. W. Bioorg. Med. Chem. 2006, 14, 4980. and
references cited therein.
11. For leading references on the procedures used for the other viral assays see (a)
Rajappan, V. P.; Schneller, S. W.; Williams, S. L.; Kern, E. R. Bioorg. Med. Chem.
2002, 10, 883; (b) Siddiqi, S. M.; Chen, X.; Schneller, S. W.; Ikeda, S.; Snoeck, R.;
Andrei, G.; Balzarini, J.; De Clercq, E. J. Med. Chem. 1994, 37, 551; (c) Seley, K. L.;
Schneller, S. W.; Korba, B. Nucleosides Nucleotides 1997, 16, 2095. and,; (d)
http://www.usu.edu/iar/Brochure/brochure.html (January 4, 2009).
2. Roy, A.; Schneller, S. W.; Keith, K. A.; Hartline, C. B.; Kern, E. R. Bioorg. Med.
Chem. 2005, 13, 4443.
3. Siddiqi, S. M.; Oertel, F. P.; Chen, X.; Schneller, S. W. J. Chem. Soc., Chem.
Commun. 1993, 708.
4. Kitade, Y.; Ando, T.; Yamaguchi, T.; Hori, A.; Nakanishi, M.; Ueno, Y. Bioorg. Med.
Chem. 2006, 14, 5578.