Synthesis and activity of substituted 4-(indazol-3-yl)phenols as pathway-selective estrogen receptor ligands useful in the treatment of rheumatoid arthritis.
Article Details
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Steffan RJ, Matelan E, Ashwell MA, Moore WJ, Solvibile WR, Trybulski E, Chadwick CC, Chippari S, Kenney T, Eckert A, Borges-Marcucci L, Keith JC, Xu Z, Mosyak L, Harnish DC
Synthesis and activity of substituted 4-(indazol-3-yl)phenols as pathway-selective estrogen receptor ligands useful in the treatment of rheumatoid arthritis.
J Med Chem. 2004 Dec 16;47(26):6435-8.
- PubMed ID
- 15588074 [ View in PubMed]
- Abstract
Pathway-selective ligands for the estrogen receptor (ER) inhibit NF-kappaB-mediated inflammatory gene expression causing a reduction of cytokines, chemokines, adhesion molecules, and inflammatory enzymes. SAR development of a series of 4-(indazol-3-yl)phenols has led to the identification of WAY-169916 an orally active nonsteroidal ligand with the potential use in the treatment of rheumatoid arthritis without the classical proliferative effects associated with estrogens.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 4-(6-HYDROXY-1H-INDAZOL-3-YL)BENZENE-1,3-DIOL Estrogen receptor alpha EC 50 (nM) 298 N/A N/A Details 4-(6-HYDROXY-1H-INDAZOL-3-YL)BENZENE-1,3-DIOL Estrogen receptor alpha IC 50 (nM) 48 N/A N/A Details 4-[1-allyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol Estrogen receptor alpha IC 50 (nM) 1300 N/A N/A Details 4-[1-allyl-7-(trifluoromethyl)-1H-indazol-3-yl]benzene-1,3-diol Estrogen receptor alpha IC 50 (nM) 93 N/A N/A Details