ACS Medicinal Chemistry Letters
Page 6 of 6
(2) Itoh, T.; Hasegawa, J.; Tsujita, K.; Kanaho, Y.; Takenawa,
cyanide, tetrakis(triphenylphosphine) palladium(0), DMF,
microwave, 120–130°C, 55%. (l) TFA, CH2Cl2, rt, 87%.
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As for other pyridine derivatives 2-12 and bicyclic
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In summary, initial SAR study on HTS hits, followed by
scaffold hopping and optimization, furnished a potent,
drug-like, and in vivo-active compound, DS21360717.
Further optimization and characterization of the lead
compound will be reported in due course.
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ASSOCIATED CONTENT
Supporting Information
Synthetic procedures and characterization data of all
compounds, and information on additional studies are
AUTHOR INFORMATION
*Corresponding Author
Tel.: +81-3-3492-3131
ABBREVIATIONS
HTS, high-throughput screening; Pe, permeability coefficient;
CLtot, total body clearance; BA, bioavailability; DIPEA, N-
ethyl-N,N-diisopropylamine; MeCN, acetonitrile; THF,
tetrahydrofuran;
dimethylaminopropyl)carbodiimide;
WSCI.HCl,
1-ethyl-3-(3-
HOSu, N-
hydroxysuccinimide; DMF, N,N-dimethylformamide; EtOH,
ethyl alcohol; LDA, lithium diisopropylamide; NBS, N-
bromosuccinimide; p-TsOH, p-toluenesulfonic acid; MeOH,
methyl alcohol; TFA, trifluoroacetic acid; NMP, N-
methylpyrrolidone
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Fer-Mediated Cortactin Phosphorylation Is Associated
with Efficient Fibroblast Migration and Is Dependent on
Reactive Oxygen Species Generation during Integrin-
Mediated Cell Adhesion. Mol. Cell. Biol. 2007, 32, 6140–
6152.
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