Potent and Orally Bioavailable Zwitterion GnRH Antagonists with Low CYP3A4 Inhibitory Activity
Overview
Authors
Affiliations
Incorporation of a carboxylic acid into a series of uracil derivatives as hGnRH-R antagonists resulted in a significant reduction of CYP3A4 inhibitory activity. Highly potent hGnRH antagonists with low CYP3A4 inhibitory liability, such as 8a and 8d, were identified. Thus, 8a had a K(i) of 2.2 nM at GnRH-R and an IC(50) of 36 microM at CYP3A4.
Research advances in drug therapy of endometriosis.
Shi J, Tan X, Feng G, Zhuo Y, Jiang Z, Banda S Front Pharmacol. 2023; 14:1199010.
PMID: 37416064 PMC: 10320007. DOI: 10.3389/fphar.2023.1199010.
Uterine fibroids: an update on current and emerging medical treatment options.
Farris M, Bastianelli C, Rosato E, Brosens I, Benagiano G Ther Clin Risk Manag. 2019; 15:157-178.
PMID: 30774352 PMC: 6350833. DOI: 10.2147/TCRM.S147318.
Recent Development of Non-Peptide GnRH Antagonists.
Tukun F, Olberg D, Riss P, Haraldsen I, Kaass A, Klaveness J Molecules. 2017; 22(12).
PMID: 29232843 PMC: 6149776. DOI: 10.3390/molecules22122188.
Durust Y, Ozer B, Kariuki B, Cariuki B Mol Divers. 2015; 19(2):213-30.
PMID: 25754077 DOI: 10.1007/s11030-015-9577-3.