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Discovery of Vilaprisan (BAY 1002670): A Highly Potent and Selective Progesterone Receptor Modulator Optimized for Gynecologic Therapies
Author(s) -
Möller Carsten,
Bone Wilhelm,
Cleve Arwed,
Klar Ulrich,
Rotgeri Andrea,
Rottmann Antje,
SchultzeMosgau MarcusHillert,
Wagenfeld Andrea,
Schwede Wolfgang
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800487
Subject(s) - ulipristal acetate , mifepristone , progesterone receptor , pharmacology , uterine fibroids , drug discovery , clinical trial , drug , medicine , bioinformatics , biology , gynecology , estrogen receptor , family planning , population , research methodology , pregnancy , environmental health , cancer , breast cancer , genetics
Progesterone plays an important role in the female reproductive system. However, there is also evidence that gynecologic disorders/diseases such as uterine fibroids and endometriosis are progesterone‐dependent. Steroidal and non‐steroidal selective progesterone receptor modulators (SPRMs) have shown potential for the treatment of such diseases. Steroidal SPRMs, including mifepristone and ulipristal acetate, have proven effective in clinical trials. However, several steroidal SPRMs containing a dimethylamino substituent have been associated with elevated liver enzymes in patients. An earlier drug discovery program identified lonaprisan as a highly selective SPRM that did not show drug‐related change in liver enzyme activity. Building on data obtained from that work, here we describe the research program that culminated in the discovery of a novel steroidal SPRM, vilaprisan, which combines an extremely high potency with very favorable drug metabolism and pharmacokinetic properties. Vilaprisan has entered clinical development and is currently undergoing phase 3 clinical trials.