Discovery of Apararenone (MT-3995) as a Highly Selective, Potent, and Novel Nonsteroidal Mineralocorticoid Receptor Antagonist
| Autor: | Toru Iijima, Makoto Katoh, Kei Takedomi, Yasuo Yamamoto, Hidenori Akatsuka, Naritoshi Shirata, Akito Nishi, Misae Takakuwa, Yoshinori Watanabe, Hitomi Munakata, Naomi Koyama, Tomoko Ikeda, Taku Iguchi, Harutoshi Kato, Kohei Kikkawa, Takayuki Kawaguchi |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Medicinal Chemistry. 65:8127-8143 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.2c00402 |
| Popis: | Overactivation of the mineralocorticoid receptor (MR) is involved in many diseases, such as hypertension, kidney disease, and heart failure. Thus, MR antagonists (MRAs) are expected to be beneficial to patients with these diseases. In order to identify novel nonsteroidal MRAs that overcome the issues of already marketed steroidal MRAs, we searched for new compounds guided by our hypothesis that T-shaped compounds with a hydrophobic core structure, two polar functional groups at both extremities able to interact with MR, and a bulky substituent that can interfere with the folding of the C-terminal helix 12 may exhibit antagonist activity toward MR. We discovered that the novel 1,4-benzoxazin-3-one derivative |
| Databáze: | OpenAIRE |
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