The present invention relates to a synthetic process for the preparation of a novel class of androgen receptor targeting agents (ARTA) which demonstrate androgenic and anabolic activity of a nonsteroidal ligand for the androgen receptor. The agents define a new subclass of compds. which are selective androgen receptor modulators (SARM) which are useful for (a) male contraception; (b) treatment of a variety of hormone-related conditions, for example conditions associated with Androgen Decline in Aging Male (ADAM), such as fatigue, depression, decreased libido, sexual dysfunction, erectile dysfunction, hypogonadism, osteoporosis, hair loss, anemia, obesity, sarcopenia, osteopenia, osteoporosis, and alterations in mood and cognition; (c) treatment of conditions associated with Androgen Decline in Female (ADIF), such as sexual dysfunction, decreased sexual libido, hypogonadism, sarcopenia, osteopenia, osteoporosis, alterations in cognition and mood, depression, anemia, hair loss, obesity and endometriosis, (d) treatment and/or prevention of chronic muscular wasting; (e) decreasing the incidence of, halting or causing a regression of prostate cancer; (f) oral androgen replacement; (g) preventing and/or treating dry eye conditions; (h) treatment and/or prevention of benign prostate hyperplasia (BPH); (i) inducing apoptosis in a cancer cell; (j) treatment and/or prevention of cancers of female sexual organs such as breast cancer, uterine cancer and ovarian cancer; and/or other clin. therapeutic and/or diagnostic areas. The process of the present invention is suitable for large-scale preparation, since all of the steps give rise to highly pure compds., thus avoiding complicated purification procedures which ultimately lower the yield. Thus the present invention provides methods for the synthesis of non-steroidal agonist compds., that can be used for industrial large-scale synthesis, and that provide highly pure products in high yield.
Please note: The titles for patent records in CAplus are routinely enhanced to better describe the claimed invention. In this example, the original title of both the U.S. equivalent and the PCT is Large-scale synthesis of selective androgen receptor modulators. For the CAplus record, this title was enhanced to read Large-scale synthesis of selective androgen receptor modulators for the diagnostic and therapeutic uses in androgen-related disorders. CAS originally indexed the PCT publication (WO 2004062612 A2) as the first published record of the invention. The original patent application showed five inventors, but by the time the patent was granted, only three of the inventors were listed in the grant. Finally, the original application showed the inventors as rights holders, and subsequently, resources from the U.S. Patent Office show both the University of Tennessee Research Foundation and the GTx Corporation as having rights to the patent.
View the full-text U.S. patent from USPTO.