Design, Synthesis, and Biological Characterization of Orally Active 17β-Hydroxysteroid Dehydrogenase Type 2 Inhibitors Targeting the Prevention of Osteoporosis.
Administration, Oral
Animals
Bone Density Conservation Agents
/ administration & dosage
Drug Delivery Systems
/ methods
Drug Design
Enzyme Inhibitors
/ administration & dosage
Estradiol Dehydrogenases
/ antagonists & inhibitors
Female
Humans
Mice
Mice, Inbred C57BL
Osteoporosis
/ enzymology
Rats
Rats, Wistar
Journal
Journal of medicinal chemistry
ISSN: 1520-4804
Titre abrégé: J Med Chem
Pays: United States
ID NLM: 9716531
Informations de publication
Date de publication:
08 08 2019
08 08 2019
Historique:
pubmed:
26
7
2019
medline:
11
6
2020
entrez:
26
7
2019
Statut:
ppublish
Résumé
Osteoporosis is predominantly treated with drugs that inhibit further bone resorption due to estrogen deficiency. Yet, osteoporosis drugs that not only inhibit bone resorption but also stimulate bone formation, such as potentially inhibitors of 17β-hydroxysteroid dehydrogenase type 2 (17β-HSD2), may be more efficacious in the treatment of osteoporosis. Blockade of 17β-HSD2 is thought to increase intracellular estradiol and testosterone in bone, thereby inhibiting bone resorption by osteoclasts and stimulating bone formation by osteoblasts, respectively. We here describe the design, synthesis, and biological characterization of a novel bicyclic-substituted hydroxyphenylmethanone 17β-HSD2 inhibitor (compound
Identifiants
pubmed: 31343176
doi: 10.1021/acs.jmedchem.9b00932
doi:
Substances chimiques
Bone Density Conservation Agents
0
Enzyme Inhibitors
0
Estradiol Dehydrogenases
EC 1.1.1.62
HSD17B2 protein, human
EC 1.1.1.62
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM