Global Discovery Chemistry, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA.
Bioorg Med Chem Lett. 2010 Aug 1;20(15):4324-7. doi: 10.1016/j.bmcl.2010.06.086. Epub 2010 Jun 19.
Aldosterone, the final component of the renin-angiotensin-aldosterone system, plays an important role in the pathophysiology of hypertension and congestive heart failure. Aldosterone synthase (CYP11B2) catalyzes the last three steps of aldosterone biosynthesis, and as such appears to be a target for the treatment of these disorders. A sulfonamide-imidazole scaffold has proven to be a potent inhibitor of CYP11B2. Furthermore, this scaffold can achieve high levels of selectivity for CYP11B2 over CYP11B1, a key enzyme in the biosynthesis of cortisol.
醛固酮是肾素-血管紧张素-醛固酮系统的最后一个组成部分，在高血压和充血性心力衰竭的病理生理学中起着重要作用。醛固酮合酶（CYP11B2）催化醛固酮生物合成的最后三个步骤，因此似乎是这些疾病治疗的靶点。磺酰胺-咪唑支架已被证明是 CYP11B2 的有效抑制剂。此外，该支架可以实现对 CYP11B2 相对于 CYP11B1（皮质醇生物合成的关键酶）的高选择性。
