ACS Medicinal Chemistry Letters
Letter
Funding
These analogues inhibit fibroblast-mediated cell scattering in a
dose-dependent manner.
This work was partially supported by Southern Research and an
Alabama Innovation Fund grant (to R.A.G., L.K.). T.E.M.
acknowledges support from the American Cancer Society,
ACS-IRG-96-153-10.
Compounds 6 and 8a−8f were examined in an in vitro
ADME assay panel. These analogues have good solubility (47
to 91 μM) and LogD < 2 at pH 7.4 due to the basic
phenylamidine functionality (pKa > 11). In human and mouse
liver microsomes, the results vary with the 5-substituent (see SI
Table 1). Compound 6 is stable in mouse and human
microsomes and was examined in a mouse IV/PO
pharmacokinetics model (Figure 3). Compound 6 has
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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We thank John Gerdes and J. Robert Bostwick for their advice
and useful discussions in the preparation of this manuscript.
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
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AUTHOR INFORMATION
Corresponding Author
Author Contributions
All authors contributed to this manuscript and have given
approval to the final version.
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