Discovery and in Vivo Evaluation of Potent Dual CYP11B2 (Aldosterone Synthase) and CYP11B1 Inhibitors
| Autor: | Erik Meredith, Michael Paul Capparelli, Gary Michael Ksander, Chang Rao, Robin Burgis, Julien Papillon, Lauren G. Monovich, Dean F. Rigel, Alok K. Singh, Arco Y. Jeng, Chii-Whei Hu, Karl Miranda, Daniel LaSala, Qian Liu, Fumin Fu, Michael E. Beil, Qi-Ying Hu, Patrick J. Morris |
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| Rok vydání: | 2013 |
| Předmět: |
Aldosterone synthase
chemistry.chemical_classification Aldosterone Cardiovascular pathology biology business.industry Organic Chemistry Pharmacology medicine.disease Biochemistry In vitro chemistry.chemical_compound Enzyme chemistry In vivo Heart failure Drug Discovery medicine biology.protein Steroid 11-beta-hydroxylase business |
| Zdroj: | ACS medicinal chemistry letters. 4(12) |
| ISSN: | 1948-5875 |
| Popis: | Aldosterone is a key signaling component of the renin-angiotensin-aldosterone system and as such has been shown to contribute to cardiovascular pathology such as hypertension and heart failure. Aldosterone synthase (CYP11B2) is responsible for the final three steps of aldosterone synthesis and thus is a viable therapeutic target. A series of imidazole derived inhibitors, including clinical candidate 7n, have been identified through design and structure–activity relationship studies both in vitro and in vivo. Compound 7n was also found to be a potent inhibitor of 11β-hydroxylase (CYP11B1), which is responsible for cortisol production. Inhibition of CYP11B1 is being evaluated in the clinic for potential treatment of hypercortisol diseases such as Cushing’s syndrome. |
| Databáze: | OpenAIRE |
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