Estrogen receptor 3-modulator

Huffman MA, Rosen JD, Farr RN, Lynch JE. Synthesis of a selective estrogen receptor (3-modulator via asymmetric phase-transfer catalysis. Tetrahedron 2007 63(21) 4459-4463. 

Selective estrogen receptor modulators (SERMs) are synthetic compounds with partially agonistic and partially antagonistic estrogenic properties. In bone, SERMs inhibit bone resorption via the mechanisms known for estrogens. Major SERMs are tamoxifen, a triphenylethylene compound, and raloxifene. In postmenopausal women, the latter has been shown to prevent bone loss and to reduce fracture risk by 40%. 

BRZEZiNSKi A and DEBI A (1999) Ph)4oestrogens the natural selective estrogen receptor modulators Eur J Obstet Gynecol Reprod Biol. 85 (1) 47-51. 

SETCHELL K D (2001) Soy isoflavones-benefits and risks from nature s selective estrogen receptor modulators (SERMs). J Am Coll Nutr. 20 (5 Suppl) 354S-362S. 

Liu, H. Liu, J. van Breemen, R. B. Thatcher, G. R. Bolton, J. L. Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids 4 -fhioro substitution prevents quinoid formation. Chem. Res. Toxicol. 2005, 18, 162-173. 

DVT, deep vein thrombosis HIT, heparin-induced thrombocytopenia PAI-I, plasminogen activator inhibitor PE, pulmonary embolism SERM, selective estrogen receptor modulator VTE, venous thromboembolism. 

GP glycoprotein SERM selective estrogen receptor modulator... 

SERM, selective estrogen receptor modulator SERD, selective estrogen receptor down regulator LHRH, luteinizing hormone-releasing hormone. 

In conclusion, we have developed an efficient asymmetric synthesis of the selective estrogen receptor modulator 1. This process was scaled up in the pilot plant for the early steps in the synthetic route and in kilo laboratory scale for the later steps and finally 4 kg of the final product was made. The key process development and project support milestones are summarized below ... 

Zajchowski et al. [107] showed comparison of expression profiles between 38 different estrogen receptor-modulating compounds. An intial study was run based on the results of profiling of 24 combinations of cells and genes with estrogen, tamoxifen, raloxifene and ICI 164384 (a pure ER antagonist). Using the optimized assay panel derived from these studies, the 38 compounds were then profiled and classi-... 

Zajchowski DA et al. Identification of selective estrogen receptor modulators by their gene expression fingerprints. J Biol Chem 2000 275 15885-15894. 

Hypercoagulable states include malignancy activated protein C resistance deficiency of protein C, protein S, or antithrombin factor VIII or XI excess antiphospholipid antibodies and other situations. Estrogens and selective estrogen receptor modulators have been linked to venous thrombosis, perhaps due in part to increased serum clotting factor concentrations. Although a thrombus can form in any part of the venous circulation, the majority of thrombi begin in the lower extremities. Once formed, a venous... 

Selective estrogen-receptor modulators prevent bone loss and vertebral ... 

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