Download MendeleyConformationally constrained farnesoid X receptor (FXR) agonists: Naphthoic acid-based analogs of GW 4064.
Akwabi-Ameyaw, A., Bass, J.Y., Caldwell, R.D., Caravella, J.A., Chen, L., Creech, K.L., Deaton, D.N., Jones, S.A., Kaldor, I., Liu, Y., Madauss, K.P., Marr, H.B., McFadyen, R.B., Miller, A.B., III, F.N., Parks, D.J., Spearing, P.K., Todd, D., Williams, S.P., Wisely, G.B.(2008) Bioorg Med Chem Lett 18: 4339-4343
- PubMed: 18621523
- DOI: https://doi.org/10.1016/j.bmcl.2008.06.073
- Primary Citation of Related Structures:
3DCT, 3DCU - PubMed Abstract:
Starting from the known FXR agonist GW 4064 1a, a series of stilbene replacements were prepared. The 6-substituted 1-naphthoic acid 1b was an equipotent FXR agonist with improved developability parameters relative to 1a. Analog 1b also reduced the severity of cholestasis in the ANIT acute cholestatic rat model.
Organizational Affiliation:
Department of Medicinal Chemistry, GlaxoSmithKline, 5 Moore Drive, PO Box 13398, Research Triangle Park, NC 27709, USA.
