Design and synthesis of novel δ opioid receptor agonists with an azatricyclodecane skeleton for improving blood-brain barrier penetration
| Autor: | Hiroshi Nagase, Shigeto Hirayama, Toshihiro Takahashi, Kohei Hayashida, Takashi Iwai, Yoshikazu Watanabe, Eriko Nakata, Saito Daisuke, Junichi Sakai, Takashi Kanda, Hideaki Fujii, Tomio Yamakawa |
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| Rok vydání: | 2017 |
| Předmět: |
Stereochemistry
medicine.drug_class Clinical Biochemistry Pharmaceutical Science 010402 general chemistry Administration Cutaneous 01 natural sciences Biochemistry chemistry.chemical_compound Mice Opioid receptor Blood brain barrier penetration Receptors Opioid delta Drug Discovery medicine Animals Humans Methylene Molecular Biology Carbon atom 010405 organic chemistry Organic Chemistry In vitro toxicology Cyclodecanes Skeleton (computer programming) 0104 chemical sciences Analgesics Opioid chemistry Permeability (electromagnetism) Blood-Brain Barrier Drug Design Molecular Medicine Bbb permeability |
| Zdroj: | Bioorganicmedicinal chemistry letters. 27(15) |
| ISSN: | 1464-3405 |
| Popis: | We designed and synthesized novel δ opioid receptor (DOR) agonists 3a – i with an azatricyclodecane skeleton, which was a novel structural class of DOR agonists. Among them, 3b exhibited high values of binding affinity and potent agonistic activity for the DOR that were approximately equivalent to those of 2 which bore an oxazatricyclodecane skeleton. In vitro assays using the blood-brain barrier (BBB) permeability test kit supported the idea that 3b achieved an excellent BBB permeability by converting an oxygen atom of 2 to a carbon atom (methylene group) in the core skeleton. As a result, 3b showed potent antinociceptive effects. |
| Databáze: | OpenAIRE |
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