Selective estrogen receptor modulators tamoxifen

The clinical uses of anastrozole (decreases estrogen synthesis), danazol (deaeases ovarian steroid synthesis), clomiphene (decreases feedback inhibition), and the selective estrogen-receptor modulators tamoxifen and raloxifene are considered. 

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%. 

Aromatase inhibitors (including anastrozole, letrozole, aminoglutethimide, exemestane, formestane, testolactone), selective estrogen receptor modulators—SERMs (including raloxifene, tamoxifen, toremifene), clomiphene, cyclofenil, fulvestrant Diuretics, amiloride, bumetanide, canrenone, chlorthalidone, etacrynic acid, furosemide, indapamide, metolazone, spironolactone, thiazides, triamterene... 

Idoxifene is another of the newer selective estrogen receptor modulators (SERMs), and preclinical data show that it has greater antiestrogenic activity than tamoxifen but lower estrogenic activity. It is not yet clear whether this affects its degree of usefulness or safety when it is used, for example, in cases of metastatic breast cancer. In comparisons of the two drugs in such patients the desired effects were similar and the incidence of adverse effects was essentially the same (14). 

There also exist a class of ligands referred to as SERMs (selective estrogen receptor modulators) that display tissue-selective pharmacology [13]. Raloxifene and tamoxifen are two clinically used SERMs for which structures are available. Crystal structures of the estrogen receptor bound to different ligands (estradiol, tamoxifen, or raloxifene) reveal that ligands of different sizes and shapes induce a spectrum of receptor conformational states. These states can be interpreted by the cellular complexion of co-regulators and the environment of the local promoter of... 

Tamoxifen 219 is an important selective estrogen receptor modulator (SERM) that has anti-estrogenic properties of value for the treatment of breast cancer. It does, however, have some undesired side effects. Thus, the development of analogs is of great interest. A pyridyl derivative 218 was assembled via the Suzuki reaction of 217 with 3-iodopyridine 152 [77]. 

---