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Letter

Synthesis and Activity of Substituted 4-(Indazol-3-yl)phenols as Pathway-Selective Estrogen Receptor Ligands Useful in the Treatment of Rheumatoid Arthritis

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Robert J. Steffan,*^† Edward Matelan,^† Mark A. Ashwell,^‡ William J. Moore,^† William R. Solvibile,^† Eugene Trybulski,^† Christopher C. Chadwick,^† Susan Chippari,^‡ Thomas Kenney,^‡ Amy Eckert,^‡ Lisa Borges-Marcucci,^‡ James C. Keith,^§ Zhang Xu, Lydia Mosyak, and Douglas C. Harnish^‡

Chemical and Screening Sciences and Cardiovascular/Metabolic Diseases, Wyeth Research, 500 Arcola Road, Collegeville, Pennsylvania 19426, and Chemical and Screening Sciences, Wyeth Research, Cambridge, Massachusetts 02140

J. Med. Chem., 2004, 47 (26), pp 6435–6438

DOI: 10.1021/jm049194+

Publication Date (Web): November 12, 2004

Corresponding author: phone (484)865-4648, fax (484) 865-9398, e-mail steffar@wyeth.com.

†

Chemical and Screening Sciences, Wyeth Research, Collegeville.

‡

Cardiovascular/Metabolic Diseases, Wyeth Research, Collegeville.

Current address: ArQule, 19 Presidential Way, Woborn, MA 01741.

Current address: Life Diagnostics Inc., West Chester PA 19380.

Cardiovascular/Metabolic Diseases, Wyeth Research, Cambridge.

Chemical and Screening Sciences, Wyeth Research, Cambridge.

Abstract

Pathway-selective ligands for the estrogen receptor (ER) inhibit NF-κB-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.

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Published In Issue December 16, 2004
Received October 6, 2004

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Letter

Synthesis and Activity of Substituted 4-(Indazol-3-yl)phenols as Pathway-Selective Estrogen Receptor Ligands Useful in the Treatment of Rheumatoid Arthritis

Abstract

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SciFinder Links

History

Recommend & Share

Related Content

Estrogen Receptor Dependent Inhibitors of NF-κB Transcriptional Activation-1 Synthesis and Biological Evaluation of Substituted 2-Cyanopropanoic Acid Derivatives: Pathway Selective Inhibitors of NF-κB, a Potential Treatment for Rheumatoid Arthritis

Novel Indolylindazolylmaleimides as Inhibitors of Protein Kinase C-β: Synthesis, Biological Activity, and Cardiovascular Safety

Structure-Guided Optimization of Estrogen Receptor Binding Affinity and Antagonist Potency of Pyrazolopyrimidines with Basic Side Chains

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