title: Optimization of hydroxybenzothiazoles as novel potent and selective inhibitors of 17β-HSD1.
abstract: 17β-HSD1 is a novel target for the treatment of estrogen-dependent diseases, as it catalyzes intracellular estradiol formation. Starting from two recently described compounds, highly active and selective inhibitors were developed. Benzoyl 6 and benzamide 17 are the most selective compounds toward 17β-HSD2 described so far. They also showed a promising profile regarding activity in T47-D cells, selectivity toward ERα and ERβ, inhibition of hepatic CYP enzymes, metabolic stability, and inhibition of marmoset 17β-HSD1 and 17β-HSD2.
authors.affiliation: Pharmaceutical and Medicinal Chemistry, Saarland University, Campus C23, D-66123 Saarbrücken, Germany.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Spadaro
authors.forename: Martin
authors.initials: M
authors.lastname: Frotscher
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002144:Callithrix; D002460:Cell Line; D065607:Cytochrome P-450 Enzyme Inhibitors; D004960:Estradiol Dehydrogenases / Q000037:antagonists & inhibitors*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011869:Radioligand Assay; D013329:Structure-Activity Relationship
chemical_list: D052160:Benzothiazoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; C523763:HSD17B2 protein, human