Highly Potent 17β-HSD2 Inhibitors with a Promising Pharmacokinetic Profile for Targeted Osteoporosis Therapy was written by Siebenbuerger, Lorenz;Hernandez-Olmos, Victor;Abdelsamie, Ahmed S.;Frotscher, Martin;van Koppen, Chris J.;Marchais-Oberwinkler, Sandrine;Scheuer, Claudia;Laschke, Matthias W.;Menger, Michael D.;Boerger, Carsten;Hartmann, Rolf W.. And the article was included in Journal of Medicinal Chemistry in 2018.Recommanded Product: 936902-12-4 This article mentions the following:
Intracellular elevation of E2 levels in bone by inhibition of 17β hydroxysteroid dehydrogenase type 2 (17β-HSD2) without affecting systemic E2 levels is an attractive approach for a targeted therapy against osteoporosis, a disease which is characterized by loss of bone mineral d. Previously identified inhibitor A shows high potency on human and mouse 17β-HSD2, but poor pharmacokinetic properties when applied perorally in mice. A combinatorial chem. approach was utilized to synthesize truncated derivatives of A, leading to highly potent compounds with activities in the low nanomolar to picomolar range. Compound 33, comparable to A in terms of inhibitor potency against both human and mouse enzymes, displays high in vitro metabolic stability in human and mouse liver S9 fraction as well as low toxicity and moderate hepatic CYP inhibition. Thus, compound 33 showed a highly improved peroral pharmacokinetic profile in comparison to A, making 33 a promising candidate for further development. In the experiment, the researchers used many compounds, for example, 5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazole (cas: 936902-12-4Recommanded Product: 936902-12-4).
5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)benzo[d]oxazole (cas: 936902-12-4) belongs to benzoxazole derivatives. The benzoxazole moiety is widely found in various natural compounds, which are often found to be biologically active. A number of marketed drugs are available having benzoxazole as core active moiety like, nonsteroidal anti-inflammatory drug (NSAID)—flunoxaprofen, benoxaprofen, antibiotic—calcimycin.Recommanded Product: 936902-12-4
Referemce:
Benzoxazole – Wikipedia,
Benzoxazole | C7H5NO – PubChem