Y. Xu et al. / Bioorg. Med. Chem. Lett. 20 (2010) 2942–2945
2945
Table 1
purpose of this modification was to orient the side chain to a proper
conformation and form hydrogen-bonding and hydrophobic inter-
action with CACYP51. The design rationalewas confirmedby flexible
molecular docking. In vitro antifungal assay indicated that most of
the synthesized new azoles showed good activity against important
fungal pathogens. The MIC80 values of several compounds are in the
a
Antifungal in vitro activities of the compounds (MIC80, l )
g mLÀ1
Compd C. alb.
C. tro.
C. par.
C. kru
C. neo
T. rub.
A. fum.
12
1
1
16
4
1
16
0.25
>64
1
1
1
1
1
1
4
1
10a
10b
10c
10d
10e
10f
10g
10h
10i
1
1
0.0625
0.004
0.004
0.004
0.0625 0.25
0.016
0.016
0.0625 0.25
0.0625 0.25
0.016
0.004
1
0.0625
0.016
0.016
0.016
0.001
0.001
0.016
0.016
0.004
0.016
0.016
0.004
0.016
0.016
0.0625
16
0.016
0.004
0.016
0.016
0.0625
0.016
0.0625
0.016
0.016
0.016
0.016
0.016
0.016
0.25
16
0.004
0.001
0.016
0.0625
0.0625
0.016
0.0625
0.001
0.016
0.0097
0.004
0.004
0.004
0.25
64
0.25
0.0625
0.25
0.0625
0.0625
0.0625
0.016
0.0625
0.0625
0.0625
0.0625
range of 0.001–0.004 lg/mL, suggesting that they are promising
leads for the discovery of novel antifungal agents.
0.25
0.25
Acknowledgments
1
This work was supported by the National Natural Science Foun-
dation of China (Grant No. 30973640), Shanghai Rising-Star Pro-
gram (Grant No. 09QA1407000) and Shanghai Leading Academic
Discipline Project (Project No. B906).
10j
10k
10l
0.25
0.25
0.0625 0.25
0.0625
0.0625
0.0625
0.016
0.0625
16
4
16
4
16
1
1
1
1
0.0625 0.25
10m
10n
10o
10p
10q
10r
10s
10t
10u
10v
10w
10x
10y
15a
15b
FCZ
ICZ
0.016
0.016
0.25
64
0.25
0.25
0.25
64
4
1
Supplementary data
64
64
64
64
64
64
64
64
64
64
1
1
4
4
4
Supplementary data (experimental protocols, NMR and HRMS data
for the synthesized compounds) associated with this article can be
16
16
16
16
64
16
16
16
0.0625
0.016
0.25
0.016
0.004
64
64
64
64
64
64
64
64
0.25
0.016
1
0.0625
0.004
64
64
64
64
64
64
64
64
64
64
64
64
16
64
64
64
4
16
16
64
16
16
16
16
16
0.0625
0.016
0.0625
0.004
0.004
16
16
16
16
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a
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In summary, computer modeling was successfully used in ra-
tional design of novel antifungal azoles. Starting from an inactive
azole derivative, we transferred its substituted piperidin-4-imino
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