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The compounds were tested (concentration range: 0.1–10 mg/
mL) for their ability to inhibited IMPDH type II.30 In this assay,
MPA inhibited IMPDH type II with an IC50 of 1.5
amide-based inhibitors that were evaluated in the current study
inhibited IMPDH type II with an IC50 of less than 10 M. The com-
pounds 2d, 2e, 2h, 2m and 2n inhibited IMPDH type II with IC50
values of 2.1, 4.5, 8.8, 3.2 and 2.8 M, respectively.
lM. Some of the
l
l
In summary, we have synthesized 35 isobenzofuran-derived
analogs and evaluated their activities on T-cell proliferation and
IMPDH type II. Generally, the
a,b-unsaturated amide series were
more potent than the diamide and urea series. The structure–activ-
ity relationship of isobenzofuran-derived analogs for immunosup-
pressive activity was also evaluated. From the lymphoproliferation
assay results, the analogs 2d, 2e, 2h and 2j proved more potent
activities than MPA, whereas the analogs 2k, 2m, 2n, 4c and 5d
exhibited an equipotent inhibitory activity compared to MPA. In
addition, the ability of the compounds to inhibit IMPDH type II
activity in vitro was tested. The analogs 2d, 2e, 2m and 2n inhib-
ited IMPDH type II as effectively as MPA. Further evaluation of
the immunosuppressant efficacy using other immunological tests
is currently under way to elucidate their potential therapeutic
use and establish the relationship between efficacy and toxicity
in vivo.
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Acknowledgment
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The authors would like to thank New Drug Research& Develop-
ment Center of North China Pharmaceutical Group Corporation for
providing biological data.
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Supplementary data
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Supplementary data associated with this article can be found, in
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