The Design, Structure–Activity, and Kinetic Studies of 3-Benzyl-5-oxa-1,2,3,4-Tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl Sulfamates as Steroid Sulfatase Inhibitors
| Autor: | Chiao-Nien Chang, I-Chun Lin, Tzung-Sheng Lin, Pei-Fang Chiu, Yeh-Lin Lu, Manmath Narwane, I-Chen Liu, Yue Hng, Keng-Chang Tsai, Mei-Hsiang Lin, Yves S. Y. Hsieh, Mei-Jou Chen, Pi-Hui Liang |
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| Rok vydání: | 2022 |
| Předmět: |
History
Polymers and Plastics Placenta Organic Chemistry Biochemistry Industrial and Manufacturing Engineering Kinetics Structure-Activity Relationship Pregnancy Drug Design Drug Discovery MCF-7 Cells Humans Female Steryl-Sulfatase Enzyme Inhibitors Sulfonic Acids Business and International Management Molecular Biology |
| Zdroj: | SSRN Electronic Journal. |
| ISSN: | 1556-5068 |
| Popis: | Steroid sulfatase inhibitors block the local production of estrogenic steroids and are attractive agents for the treatment of estrogen-dependent cancers. Inspiration of coumarin-based inhibitors, we synthesized thirty-two 5-oxa-1,2,3,4-tetrahydro-2H-chromeno-(3,4-c)pyridin-8-yl sulfamates, focusing on the substitution derivatives on the adjacent phenyl ring and evaluated their abilities to block STS from human placenta and MCF-7 cells. SAR analysis revealed that the incorporation of chlorine at either meta and/or para position of the adjacent phenyl ring of the tricyclic skeleton enhanced STS inhibition. Di-substitutions at the adjacent phenyl ring were superior to mono and tri-substitutions. Further kinetic analysis of these compounds revealed that chloride-bearing compounds, such as 19m, 19v, and 19w, had K |
| Databáze: | OpenAIRE |
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