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In conclusion, a new series of pyrrolo[3,2-b]pyridine derivatives
was synthesized based on our previous literature studies, by focus-
ing on the structure–activity relationship studies of the pyrrol-
o[2,3-d]pyrimidine derivatives. Among all of these derivatives,
compounds Ir25 and It25 having 5-benzylamide substituted
40-amide moieties showed the most potent antiproliferative activ-
ity against A375 human melanoma cell line. Further modification
of these compounds in order to improve their potency is currently
in progress. Our ultimate goal is to identify several compounds that
are highly potent and highly selective against melanoma cells.
22. David, J. A.; Robert, A. E.; Diane, E. F.; Ben, Z. Org. Process Res. Dev. 2004, 8, 62.
23. A375P cells were purchased from American Type Culture Collection (ATCC,
Rockville, MD, US) and maintained in DMEM medium (Welgene, Daegu, Korea)
supplemented with 10% FBS (Welgene) and 1% penicillin/streptomycin
(Welgene) in a humidified atmosphere with 5% CO2 at 37 °C. A375P cells
were taken from culture substrate with 0.05% trypsin–0.02% EDTA and plated
at a density of 5 ꢀ 103 cells/well in 96 well plates and then incubated at 37 °C
for 24 h in a humidified atmosphere with 5% CO2 prior to treatment of various
concentration (threefold serial dilution, 12 points) of test compounds. The
A357P cell viability was assessed by the conventional 3-(4,5-dimethylthiazol-
2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. MTT assays
were carried out with CellTiter 96Ò (Promega) according to the manufacturer’s
instructions. The absorbance at 590 nm was recorded using EnVision 2103
(Perkin Elmer; Boston, MA, US). The IC50 was calculated using GraphPad Prism
4.0 software.
Acknowledgments
We are grateful to the Korea Institute of Science and Technology
(KIST) for financial support.
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25. Ir: 1H NMR (300 MHz, DMSO-d6) d 10.74 (br s, 1H), 9.24 (br s, 1H), 8.42 (s, 1H),
8.30 (d, J = 8.1 Hz, 1H), 8.15 (d, J = 3.2 Hz, 1H), 8.10 (d, J = 8.6 Hz, 1H), 8.01–7.90
(m, 3H), 7.67 (d, J = 8.9 Hz, 1H), 7.34–7.21 (m, 6H), 6.93–6.71 (m,1H), 5.39 (br s,
1H), 4.53 (d, J = 5.9 Hz, 2H). MS m/z 549.13 (M+H)+. HRMS (FAB) Calcd for
C29H20ClF3N4O2 548.1227, found 548.1224.It: 1H NMR (300 MHz, DMSO-d6) d
10.59 (br s, 1H), 9.26 (br s, 1H), 8.27 (d, J = 6.2 Hz, 2H), 8.14–8.09 (m, 2H), 8.01–
7.90 (m, 3H), 7.69–7.56 (m, 3H), 7.37–7.29 (m, 4H), 7.25–7.21 (m, 1H), 6.92 (d,
J = 3.5 Hz, 1H), 4.53 (d, J = 6.3 Hz, 2H), 3.73 (br s, 4H), 2.96 (br s, 4H). MS m/z
600.22 (M+H)+. HRMS (FAB) Calcd for C33H28F3N5O3 599.2144, found 599.2143.