B. Hu et al. / Bioorg. Med. Chem. Lett. 18 (2008) 54–59
59
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Schuster, G. U.; Gustafsson, J.; Basso, M. D.; Nambi, P.
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9. Bradley, M. N.; Hong, C.; Chen, M.; Joseph, S. B.;
Wilpitz, D. C.; Wang, X.; Lusis, A. J.; Collins, A.; Hseuh,
W. A.; Collins, J. L.; Tangirala, R. K.; Tontonoz, P.
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R.; Quinet, E.; Savio, D.; Halpern, A.; Basso, M.; Keith,
J.; Clerin, V.; Chen, L.; Resmini, C.; Liu, Q.-Y.; Feingold,
I.; Huselton, C.; Azam, F.; Farnegardh, M.; Enroth, C.;
Bonn, T.; Goos-Nilsson, A.; Wilhelmsson, A.; Nambi, P.;
Wrobel, J. J. Med. Chem. 2006, 49, 6151; (b) Hu, B.;
Jetter, J.; Kaufman, D.; Singhaus, R.; Bernotas, R.;
Unwalla, R.; Quinet, E.; Savio, D.; Halpern, A.; Basso,
M.; Keith, J.; Clerin, V.; Chen, L.; Liu, Q.; Feingold, I.;
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3321.
In summary, modifications on previously reported
WAY-254011 via molecular modeling guided SAR study
produced a series of novel carboxylic acid based quino-
lines that showed some selectivity for LXRb over LXRa
in binding assays and reduced efficacy in the TG accu-
mulation assay, however, compounds in this series dis-
played more modest selectivity in the Gal4 functional
assays. Unwanted PPAR agonist activity was also ob-
served in this quinoline carboxylic acid series.
Acknowledgments
We thank the Wyeth Discovery Analytical Chemistry
Department for the analytical data. We also thank
Drs. Ron Magolda, Magid Abou-Gharbia, Steve Gar-
dell, and George Vlasuk for their support of this work.
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