Synthesis and anti-HCV determinant motif identification in pyranone carboxamide scaffold

Article abstract of DOI:10.1016/j.bmcl.2015.09.060

Hepatitis C Virus exhibits high genetic diversity. The current treatment for genotype-1 with ～80% sustained virologic responses is a combination of pegylated interferon, ribavirin and boceprevir/telaprevir/simeprevir which is associated with several side

Full text of DOI:10.1016/j.bmcl.2015.09.060

Accepted Manuscript
Synthesis and anti-HCV determinant motif identification in pyranone carboxa-
mide scaffold
Tuniki Balaraju, Ananda Kumar Konreddy, Afsana Parveen, Massaki Toyama,
Wataru Ito, Srinivas Karampuri, Masanori Baba, Ashoke Sharon, Chandralata
Bal
PII:
S0960-894X(15)30094-9
DOI:
http://dx.doi.org/10.1016/j.bmcl.2015.09.060
BMCL 23141
Reference:
Bioorganic & Medicinal Chemistry Letters
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Received Date:
Revised Date:
Accepted Date:
16 July 2015
19 September 2015
24 September 2015
Please cite this article as: Balaraju, T., Konreddy, A.K., Parveen, A., Toyama, M., Ito, W., Karampuri, S., Baba,
M., Sharon, A., Bal, C., Synthesis and anti-HCV determinant motif identification in pyranone carboxamide scaffold,
Bioorganic & Medicinal Chemistry Letters (2015), doi: http://dx.doi.org/10.1016/j.bmcl.2015.09.060
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com
Synthesis and anti-HCV determinant motif identification in pyranone carboxamide
scaffold
Tuniki Balarajua, Ananda Kumar Konreddya, Afsana Parveena, Massaki Toyamab, Wataru Itob, Srinivas
Karampuria, Masanori Babab, Ashoke Sharona,*, Chandralata Bala,*
a
Department of Chemistry, Birla Institute of Technology, Mesra, Ranchi-835215, India
b Division of Antiviral Chemotherapy, Center for Chronic Viral Diseases, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1,
Sakuragaoka, Kagoshima 890-8544, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Revised
Accepted
Available online
Hepatitis C Virus exhibits high genetic diversity. The current treatment for genotype-1
with ~80% sustained virologic responses is a combination of pegylated interferon,
ribavirin and boceprevir/telaprevir/simeprevir which is associated with several side
effects and need close monitoring. Therefore, novel therapies are invited for safer and
more efficient treatment. This study was designed for synthesis of new α-pyranone
carboxamide analogs for evaluation of anti-HCV activity to delineate structure-
activity relationship (SAR) and to identify anti-HCV determinant motif on this new
scaffold. Forty four new α-pyranone carboxamide analogs were synthesized. Six
potential anti-HCV candidates 11a (EC50 = 0.35 µM), 11e (EC50 = 0.48 µM), 12f (EC50
= 0.47 µM), 12g (EC50 = 0.39 µM), 12h (EC50 = 0.20 µM) and 12j (EC50 = 0.25 µM)
with lower cytotoxicity (CC50 > 20 μM) were discovered through cell based HCV
replicon system. The activity profile of forty four new α-pyranone carboxamide
analogs suggests the role of an aromatic motif in the B region to add a synergistic
effect to NHOH motif at 4-position and revels an anti-HCV activity determinants
motif under this scaffold. The biochemical assay against most promising HCV target
protein “NS3 protease and NS5B polymerase” showed no activity and open a scope to
explore new mechanism inhibitor.
Keywords:
Hepatitis C Virus
Pyranone carboxamide
Non-nucleoside inhibitor
2009 Elsevier Ltd. All rights reserved.
Hepatitis C Virus (HCV) is a positive stranded RNA virus of
Flaviviridae family that exhibits high genetic diversity.1 HCV is
classified into six major types of genomes (genotype 1-6) which
are further divided into subtypes and has different geographic
distributions.2 The major part of liver epidemiology and related
death toll corresponds to chronic HCV infection.3 The current
treatment for genotype-1 with ~80% sustained virologic
responses is a combination of pegylated interferon, ribavirin and
boceprevir/telaprevir/simeprevir.4 This therapy is associated with
flu-like symptoms, anaemia, loss of appetite, depression etc. and
need close monitoring.5, 6 Therefore, novel therapies are invited
for safer and more efficient treatment. In our previous
investigation,7 we had evaluated anti-HCV activities of new
analogs based on 4-hydroxyamino-α-pyranone carboxamide (I,
Fig. 1) with various combinations of A (phenyl/ substituted
phenyl) and B (phenyl/substituted phenyl/alkyl/alkanol/alkyl
ester/ benzyl). We observed that when A and B both were
phenyl, the compound was highly active with EC50 0.35 µM.7
However, substitution on A shown a tendency to decrease the
anti-HCV potential of compounds irrespective of whether B is
phenyl/substituted phenyl/alkyl/ alkanol/alkyl ester/benzyl.
Figure 1
4-hydroxyamino-α-pyranone carboxamide scaffold I
and the scaffold for present investigation (II).
Interestingly, B as substituted phenyl/alkyl/alkanol/benzyl and A
as phenyl, resulted highly active analogs with EC50 in the range
of 0.15-0.55 µM. Therefore, in the current study several new α-
pyranone carboxamide analogs II (Fig. 1) with; i)
A
(phenyl/thiophen-2-yl), B (substituted phenyls), C (4-NHOH) or
ii) A (phenyl/substituted phenyl), B (cycloalkyls), C (4-NHOH)
were synthesized and evaluated for anti-HCV potential to
∗Corresponding author. Tel.: +91-651-227-6531; fax: +91-651-227-5401; e-mail: asharon@bitmesra.ac.in, cbal@bitmesra.ac.in
1

delineate possible structure activity relationship (SAR). We were
also interested to investigate the determining role of 4-NHOH
moiety on the pyranone carboxamide scaffold towards anti-HCV
activity. Thus, replacement studies were carried out with very
close motif 4-NH(CH2)2OH. The role of “NH” and “OH” in the
substitution at 4-position was evaluated by replacing the 4-
substituent with a -NHOMe (OH absent) or piperidinyl (both OH
and NH absent) group.
Ketene dithioacetals are versatile synthons to generate various
key intermediates for further exploration towards several new
chemical scaffolds.8 Functionalized ketene dithioacetals (1a-h,
Scheme 1) were synthesized from the reaction of appropriate
aromatic ketones with CS2 followed by methyl iodide. Our final
compounds (11a-18a, Table 1) contain an amide bond at C-3
position on α-pyranone ring. To achieve this amide linkage, α-
pyranone-3-carboxylic acids (2a-h) were synthesized from
ketene dithioacetals (1a-h) by reacting them with
diethylmalonate (DEM) in presence of NaH.7 Appropriate amines
were coupled with 2a-h to get the key amide intermediates 3a-
10m. The SMe group at 4-position of amides was substituted by
the reaction of hydroxylamine/2-aminoethanol/piperidine/O-
methyl hydroxylamine to get the final compounds (11a-18a).9,10
All the synthesized compounds were characterized by physical
and spectroscopic analysis.
Scheme 1. Synthesis of 4-substituted α-pyranone carboxamide based analogs (11a-18a).
Reagents and conditions: i) NaH, CS2, CH3I, THF, 0 °C-rt, 4h; ii) NaH, diethylmalonate, dioxane, 0-110 °C, 6h; iii) R1NH2, HATU, DMF, rt, 1-2h; iv)
appropriate amine, NaHCO3, ethanol, 80 °C, 4h.
The anti-HCV assay of 11a-18a was carried out in cells
harbouring subgenomic HCV RNA replicons (genotype 1b) with
a luciferase reporter (LucNeo#2).11 The anti-HCV activities were
determined by their ability to reduce luciferase activity in HCV
RNA replicons. The cytotoxicities were evaluated by reduction in
number of viable cells using a tetrazolium dye method. The 50%
effective concentration (EC50) and 50% cytotoxic concentration
(CC50) were determined from the inhibition of luciferase activity
and reduction in viable cell number respectively (Table 1). The
compounds 11a-b, 11e, 12b, 12e-h, 12j were highly active with
EC50 ranging between 0.2 to 0.7 μM and in addition showed
lower cytotoxicity (CC50 > 20 μM). The compounds 11c-d, 11f-n,
12a, 12c, 12i were moderately active (EC50 ranging between 1 to
5 μM). The compounds with EC50 > 5 μM were considered
inactive. Telaprevir, a US FDA approved NS3 protease inhibitor
(EC50 = 0.36 μM, CC50 > 20 μM) was used as reference.
Compounds 11a (EC50 = 0.35 µM, CC50 > 20 μM) and 12g (EC50
= 0.39 µM, CC50 > 20 μM) were very close to telaprevir in their
biological profiles while 12h (EC50 = 0.2 µM, CC50 > 20 μM) and
12j (EC50 = 0.25 µM, CC50 > 20 μM) showed higher activity. The
anti-HCV activity assay of 12j in subgenomic HCV RNA
replicon cells is shown in Fig. 2.
evaluated to analyze the replacement of an aromatic moiety at B
with a non-aromatic. We observed drop in activity, however, still
noticeable with EC50 ranging between 2 to 5 μM. In addition,
thiophen-2-yl moiety (A) with phenyl/substituted phenyl (B), 4-
NHOH (12a-j) were evaluated and found to be equally good as
phenyl analogs with only two exceptions (12c-d). The anti-HCV
assay of eighteen other analogs (13a-b, 14a-f, 15a-f and 16a-d)
with
4-NH(CH2)2OH
and
various
combination
of
phenyl/substituted phenyl/thiophen-2-yl were carried out. None
of them were found to be active (EC50 > 5 μM). These results
suggest that an aromatic motif in the B region adds a synergistic
effect to NHOH at 4-position. This fact is further supported by
complete loss of activity in 17a (EC50 > 100 μM) and 18a (EC50
>
100 μM), in which both of them were replaced. It is important to
highlight that we have generated several other compounds based
on pyranone carboxamide scaffold without NHOH group, which
were found inactive in HCV screening (data not shown), however
showed antiviral activity against herpes simplex virus.12, 13 The
structure-based descriptors14 were analyzed and we found that
most of the compounds neither violated the Lipinski rule of 515 or
Jorgensen rule of 3.16 The synthesized compounds with
calculated log Poct/water (clogP, Table 1) of 2.7 0.1 and molecular
weight (mol. wt.) of 350 10 has potential anti-HCV activity with
EC50 < 1µM (Fig. 3). Whereas compounds of mol. wt. > 360
have higher clogP values (3.0 to 4.5) as well as were inactive.
Figure 2. Anti-HCV activity of 12j (EC50 = 0.25 µM, CC50 > 20 µM) in
subgenomic HCV RNA replicon cells (LucNeo#2). The cell viability and
luciferase activity are shown in bars with blue and brown colors respectively.
In the current study, we found that α-pyranone carboxamide
analogs (11a-f) with A as phenyl, B as substituted phenyl and C
as 4-NHOH (A, B & C: Fig. 1) were significantly potent which
supports our previous results.7 Cycloalkyl (B) with
phenyl/substituted phenyl (A) and 4-NHOH (11h-n) were
Figure 3.
Correlation of anti-HCV activity (EC50) with mol. wt.
and calculated clogP of synthesized compounds. The EC50 ≥ 5 µM was
normalized at 5 to consider as inactive compounds to add clarity in graph.
2

Table 1 Anti-HCV activities of 11a- 18a (Scheme 1) and Telaprevir (drug reference).
Comp.
no
Ar
R1
R2
EC50
CC50
M.wt
clogPa
11a
11b
11c
11d
11e
11f
11g
11h
11i
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
phenyl
Phenyl
4-F-Ph
2-OMe-phenyl
3-OMe-phenyl
2-OEt-phenyl
3-CF3-phenyl
2-NH2-phenyl
2-OH-phenyl
2-OH-5-NO2-phenyl
cyclohexyl
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
NHOH
0.35
0.63
1.1
1.2
0.48
1.7
3.5
2.3
3.3
3.2
2.9
2.2
5.0
4.1
1.3
0.65
3.8
>20
>20
>20
19
>20
14.0
>20
10.5
>20
11.4
12.8
8.8
10.1
13.9
>20
>20
>20
>20
>20
>20
>20
>20
11
>20
>20
>20
>20
>20
17
>20
>20
>20
>20
>20
>20
>20
>20
>20
>20
>20
>20
10
352.3
352.3
366.3
390.3
337.3
338.3
383.3
328.3
304.2
346.3
320.7
362.8
342.3
372.4
328.3
346.3
362.7
407.2
342.3
342.3
342.3
358.3
396.3
343.3
394.4
366.3
429.2
447.2
463.7
508.1
459.2
473.3
463.7
508.1
459.2
459.2
459.2
473.3
387.2
386.4
386.4
400.4
360.3
332.3
2.7
2.7
3.2
3.6
1.8
2.1
1.3
2.7
2.0
2.9
2.3
3.2
3.0
2.7
2.6
2.7
2.9
3.0
2.7
2.7
2.7
2.6
3.5
1.7
3.5
2.7
3.9
4.2
4.4
4.5
3.8
4.1
4.4
4.5
4.1
4.1
4.0
4.1
2.6
3.1
3.3
3.4
3.0
2.0
cyclopropyl
cyclohexyl
cyclopropyl
cyclohexyl
cyclohexyl
cyclohexyl
11j
11k
11l
4-F-Ph
4-Cl-Ph
4-Cl-Ph
11m
11n
12a
12b
12c
12d
12e
12f
12g
12h
12i
4-CH3-Ph
4-OCH3-Ph
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
Phenyl
Phenyl
3-Br-Ph
3-Br-Ph
3-Br-Ph
3-Br-Ph
3-Br-Ph
3-Br-Ph
4-Br-Ph
Phenyl
4-F-phenyl
4-Cl-phenyl
4-Br-phenyl
2-Me-phenyl
3-Me-phenyl
4-Me-phenyl
4-OMe-phenyl
3-CF3-phenyl
2-NH2-phenyl
2-OEt-phenyl
2-OH-phenyl
phenyl
6.0
0.59
0.47
0.39
0.20
1.8
0.25
>20
>20
>20
5.5
7.1
13
6
>20
10
14.4
>20
>20
14
>20
15
>20
>20
5.1
>100
>100
0.36
12j
13a
13b
14a
14b
14c
14d
14e
14f
15a
15b
15c
15d
15e
15f
16a
16b
16c
16d
17a
18a
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
NH(CH2)2OH
piperidinyl
NHOMe
4-F-phenyl
4-Cl-pheny
4-Br-phenyl
2-OMe-phenyl
2-OEt-phenyl
4-Cl-phenyl
4-Br-phenyl
2-OMe-phenyl
3-OMe-phenyl
4-OMe-phenyl
2-OEt-phenyl
2-Br-ethyl
2-OMe-phenyl
3-OMe-phenyl
2-OEt-phenyl
NH(CH2)2OH
NH(CH2)3OH
4-Br-Ph
4-Br-Ph
4-Br-Ph
4-Br-Ph
4-Br-Ph
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
thiophen-2-yl
4-F-Ph
>100
>100
>20
4-CH3-Ph
Telaprevir (Drug Reference Molecule)
aThe clogP value calculated using QikProp module of Schrodinger.
The clogP values were estimated using QikProp module of
Schrödinger Software Suite and reported in Table 1.
injectors (Berthold Technologies). The number of viable cells
was determined by a dye method using the water soluble
tetrazolium Tetracolor One® (Seikagaku Corporation), according
to the manufacturer’s instructions.
All compounds were dissolved in dimethyl sulfoxide (DMSO) at
a concentration of 20 mM or higher to exclude the cytotoxicity of
DMSO and stored at -20°C until use. Huh-7 cells containing self-
replicating subgenomic replicons with a luciferase reporter,
LucNeo#2,17 were grown and cultured in Dulbecco’s modified
Eagle medium with high glucose (Gibco/BRL) supplemented
with 10% heat-inactivated fetal bovine serum (Gibco/BRL), 100
U/ml penicillin G, and 100 µg/ml streptomycin. LucNeo#2, were
maintained in culture medium containing 1 mg/ml G418 (Nakarai
Tesque). The anti-HCV activity of the test compounds was
determined in LucNeo#2 cells by the previously described
method with some modifications.18 Briefly, the cells (5 × 103
cells/well) were cultured in a 96-well plate in the absence of
G418 and in the presence of various concentrations of the
compounds. After incubation at 37°C for 3 days, the culture
medium was removed, and the cells were washed twice with
phosphate-buffered saline (PBS). Lysis buffer was added to each
well, and the lysate was transferred to the corresponding well of a
non-transparent 96-well plate. The luciferase activity was
measured by addition of the luciferase reagent in a luciferase
assay system kit (Promega) using a luminometer with automatic
In the present study, 44 new analogs (Scheme 1, Table 1) based
on α-pyranone carboxamide scaffold were synthesized to study
the role of aromatic moiety and NHOH group towards anti-HCV
activity. Six potential anti-HCV candidates 11a (EC50 = 0.35
µM), 11e (EC50 = 0.48 µM), 12f (EC50 = 0.47 µM), 12g (EC50
=
0.39 µM), 12h (EC50 = 0.20 µM) and 12j (EC50 = 0.25 µM) with
lower cytotoxicity (CC50 > 20 μM) were discovered. We observed
that an aromatic motif in the B region adds a synergistic effect to
NHOH at 4-position and may be suggested as anti-HCV activity
determinants for the pyranone carboxamide scaffold. The
compounds with NH(CH2)2OH at 4-position had shown several
fold less activity. A quantum mechanics pKa calculation by
Jaguar module of Schrodinger for OH of NHOH and
NH(CH2)2OH showed 6.5 and 16.6 respectively.19 Therefore,
quantum calculation characterizes the strong donating nature of
OH of NHOH group over the OH of NH(CH2)2OH functional
group. This analyses hint a plausible metal chelation mechanism
involving NHOH responsible for the anti-HCV activity.20 In
3

CH3), 6.90-6.92 (d, J = 8 Hz, 2H, ArH), 7.0 (s, 1H,
pyranone), 7.2-7.4 (m, 1H, thiophen-2-yl), 7.5 (d, J = 8 Hz,
2H,Ar H), 7.93-7.96 (m, 2H, thiophen-2-yl), 10.5 (s, NH
amide), 11.0 (s, 1H, NH), 12.4 (s, 1H, OH).
Salim, M. T.; Aoyama, H.; Sugita, K.; Watashi, K.;
Wakita, T.; Hamasaki, T.; Okamoto, M.; Urata, Y.;
Hashimoto, Y.; Baba, M. Biochem. Biophysical Res.
Comm. 2011, 415, 714.
Karampuri, S.; Bag, P.; Yasmin, S.; Chouhan, D. K.; Bal,
C.; Mitra, D.; Chattopadhyay, D.; Sharon, A. Bioorg. Med.
Chem. Lett. 2012, 22, 6261.
Karampuri, S.; Ojha, D.; Bag, P.; Chakravarty, H.; Bal, C.;
Chattopadhyay, D.; Sharon, A. RSC Advances 2014, 4,
17354.
QikProp; Schr dinger, LLC, New York, NY, 2014.
Lipinski, C. A.; Lombardo, F.; Dominy, B. W.; Feeney, P.
J. Adv. Drug Deliv. Rev. 2001, 46, 3.
Jorgensen, W. L.; Duffy, E. M. Adv. Drug Deliv. Rev.
2002, 54, 355.
Goto, K.; Watashi, K.; Murata, T.; Hishiki, T.; Hijikata,
M.; Shimotohno, K. Biochem. Biophysical Res. Comm.
2006, 343, 879.
Windisch, M. P.; Frese, M.; Kaul, A.; Trippler, M.;
Lohmann, V.; Bartenschlager, R. J Virol 2005, 79, 13778.
Schr dinger, LLC, New York, NY, 2014.
addition, the assay of most active compound in this series on NS3
protease or NS5B polymerase (data not shown) did not show any
inhibitory effect on them. Though further biochemical evidence
is necessary to delineate the complete mechanism of action, this
preliminary result supports identification and discovery of
inhibitors following new mechanism. Thus, the current study
opens a future scope and may yield newer drugs for combination
therapy to strengthen the current treatment along with positive
11
12
13
effect on the appearance of drug resistant virus.
Acknowledgments
AS and CB extend their acknowledgement to SERB, DST
(SR/FT/CS-001/2009 & SR/FT/CS-069/2009) and UGC (37-
110/2009 & 39-705/2010), Delhi for providing initial grant to
establish anti-hepatitis research & infrastructure. AK and HC
thanks BIT Mesra for Institute Research Fellowship. Authors
acknowledge Dr. Reddy's Institute of Life Sciences, Hyderabad
for NMR-Mass Facility and Central Instrument Facility, BIT
Mesra for analytical support.
14
15
16
17
References and Notes
18
1
Messina, J. P.; Humphreys, I.; Flaxman, A.; Brown, A.;
Cooke, G. S.; Pybus, O. G.; Barnes, E. Hepatology 2015,
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20
Barb, A. W.; Jiang, L.; Raetz, C. R.; Zhou, P. Proc. Natl.
Acad. Sci. USA 2007, 104, 18433.
2
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7
Hajarizadeh, B.; Grebely, J.; Dore, G. J. Nat. Rev.
Gastroenterol. Hepatol. 2013, 10, 553.
Stickel, F. In Alcoholic Cirrhosis and Hepatocellular
Carcinoma; Springer, 2015. pp 113.
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Dammacco, F. J. Infection 2014, 68, 1.
Lange, C. M.; Jacobson, I. M.; Rice, C. M.; Zeuzem, S.
EMBO Mol. Med. 2014, 6, 4.
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General method for synthesis of 11a-12j, 13a-16d, 17a and
18a
8
9
Typlical procedure: To
a solution of appropriately
substituted 3a-10f (0.56 mmoles) in ethanol,
hydroxylamine hydrochloride (1.8 mmoles), NaHCO3
(1.45 mmoles) were added and refluxed for 2 h at 80 °C for
synthesis of 11a-12j. The reaction was monitored by TLC
for completion. The solvent was evaporated under reduced
pressure. Ice cold water was added into crude and so
formed precipitate was filtered and washed with ice cold
water. The dried crude product was purified on silica gel
(100-200 mesh) column chromatography with ethyl acetate
and n-hexane (20% EtOAc:n-hexane) as eluents to obtain
pure solid compound in 75-85% yield.
For synthesis of 13a-16d, 2-aminoethanol was used in
place of hydroxylamine and followed the typical procedure
as above to yield 13a-16d. A solution of compound 4c
(200 mg, 0.65 mmol) in 5 mL of dioxane, piperidine (0.98
mmol) was added then the reaction mixture was refluxed
for 5 h and followed the above procedure to yield 17a. For
synthesis of 18a, to a solution of compound 6b (200mg,
0.65 mmol) in 5mL of ethanol, O-methyl hydroxyl amine
hydrochloride (54 mg, 0.97 mmol) and potassium
carbonate (132 mg, 0.97 mmol) were added. The reaction
mixture was refluxed for 5 to 6 h and followed the above
typical procedure to yield 18a.
10
4-(hydroxyamino)-N-(4-methoxyphenyl)-2-oxo-6-
(thiophen-2-yl)-2H-pyran-3-carboxamide (12h):
Yield: 90%; mp: 196 °C; IR: (KBr) (ν, cm¯1) 3210 (OH -
Stretching), 1689 (C=O Stretching); MS (ESI) (m/z): [M+]
358.90; 1H NMR: (400 MHz, DMSO-d6): δ 3.79 (s. 3H,
4

Graphical Abstract
Leave this area blank for abstract info.
Synthesis and anti-HCV determinant motif
Identification in pyranone carboxamide scaffold
Tuniki balaraju, Ananda Kumar Konreddy, Afsana Parveen, Massaki Toyama, Wataru Ito, Srinivas
Karampuri, Masanori Baba, Ashoke Sharon, Chandralata Bal
The promising candidates with average mol.wt ~ 350 & cLogP ~ 2.7 identified with 0.5 µM of EC50 in cell based HCV
replicon system. The –NHOH motif identification as activity determinant cliff in pyranone carboxamide scaffold I.
5