The structure–activity relationship study on 2-, 5-, and 6-position of the water soluble 1,4-dihydropyridine derivatives blocking N-type calcium channels
| Autor: | Shinichi Fujita, Seiji Ohno, Seiji Niwa, Hajime Koganei, Yuki Saitou, Seinosuke Iwata, Akira Takahara, Tomoko Takeda, Tomoyuki Onishi, Takashi Yamamoto, Munetaka Tokumasu, Chika Nakanishi, Morikazu Kito, Akira Nakajo, Yukitsugu Ono, Masataka Shoji, Yoko Masuzawa |
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| Rok vydání: | 2008 |
| Předmět: |
Dihydropyridines
medicine.drug_class Stereochemistry Clinical Biochemistry Pharmaceutical Science Calcium channel blocker N-type calcium channel Biochemistry Structure-Activity Relationship chemistry.chemical_compound Calcium Channels N-Type Drug Discovery medicine Animals Humans Structure–activity relationship Molecular Biology Voltage-dependent calcium channel Calcium channel Organic Chemistry Water Biological activity Cilnidipine Calcium Channel Blockers Rats Solubility chemistry Molecular Medicine Derivative (chemistry) medicine.drug |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 18:4813-4816 |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2008.07.096 |
| Popis: | In order to find an injectable and selective N-type calcium channel blocker, we have performed the structure-activity relationship (SAR) study on the 2-, 5-, and 6-position of 1,4-dihydropyridine-3-carboxylate derivative APJ2708 (2), which is a derivative of Cilnidipine and has L/N-type calcium channel dual inhibitory activities. As a consequence of the optimization, 6-dimethylacetal derivative 7 was found to have an effective inhibitory activity against N-type calcium channels with more than 170-fold lower activity for L-type channel compared to that of APJ2708. |
| Databáze: | OpenAIRE |
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