5-(2-fluoro-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-(2-fluoro-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid
• 英文别名: 5-(4-cyano-2-fluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid；5-(4-cyano-2-fluoro-phenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid；5-(4-cyano-2-fluorophenyl)-6,7-dihydropyrrolo[1,2-c]imidazole-5-carboxylic acid
• 化学式: C₁₄H₁₀FN₃O₂
• 分子量: 271.251
• InChiKey: WQBOEVQLUXDSEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  78.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(2-fluoro-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid 以 乙醇 为溶剂， 反应 3.0h， 生成 racemic-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile
  参考文献：
  名称：

  Discovery and in Vivo Evaluation of Potent Dual CYP11B2 (Aldosterone Synthase) and CYP11B1 Inhibitors

  摘要：

  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 11 beta-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.

  DOI：

  10.1021/ml400324c
• 作为产物：
  描述：

  4-氰基-2-氟苄溴 在 盐酸 、 potassium carbonate 、 三乙胺 、 sodium iodide 、 lithium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 71.0h， 生成 5-(2-fluoro-4-cyanophenyl)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazole-5-carboxylic acid
  参考文献：
  名称：

  Discovery and in Vivo Evaluation of Potent Dual CYP11B2 (Aldosterone Synthase) and CYP11B1 Inhibitors

  摘要：

  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 11 beta-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.

  DOI：

  10.1021/ml400324c

文献信息

• Organic compounds
  申请人：Ksander Michael Gary

  公开号：US20070049616A1

  公开（公告）日：2007-03-01

  The present invention provides a compound of formula I: Said compound is inhibitor of aldosterone synthase and aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase or aromatase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, atrial fibrillation, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, inflammation, increased formation of collagen, fibrosis such as cardiac or myocardiac fibrosis and remodeling following hypertension and endothelial dysfunction, gynecomastia, osteoporosis, prostate cancer, endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycystic ovarian disease, infertility, fibrocystic breast disease, breast cancer and fibrocystic mastopathy. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种I式化合物：所述化合物是醛固酮合成酶和芳香化酶的抑制剂，因此可用于治疗由醛固酮合成酶或芳香化酶介导的疾病或疾病。因此，I式化合物可用于治疗低钾血症、高血压、充血性心力衰竭、心房颤动、肾功能衰竭，特别是慢性肾功能衰竭、再狭窄、动脉粥样硬化、X综合征、肥胖、肾病、心肌梗死后、冠心病、炎症、胶原蛋白增生、纤维化如心脏或心肌纤维化以及高血压和内皮功能障碍后的重塑，男性乳房发育过大、骨质疏松症、前列腺癌、子宫内膜异位症、子宫肌瘤、功能性子宫出血、子宫内膜增生、多囊卵巢综合征、不孕症、纤维囊性乳腺疾病、乳腺癌和纤维囊性乳房病。最后，本发明还提供了一种药物组合物。
• Organic Compounds
  申请人：Ksander Gary Michael

  公开号：US20130287789A1

  公开（公告）日：2013-10-31

  The present invention provides a compound of formula I: Said compound is inhibitor of aldosterone synthase and aromatase, and thus can be employed for the treatment of a disorder or disease mediated by aldosterone synthase or aromatase. Accordingly, the compound of formula I can be used in treatment of hypokalemia, hypertension, congestive heart failure, atrial fibrillation, renal failure, in particular, chronic renal failure, restenosis, atherosclerosis, syndrome X, obesity, nephropathy, post-myocardial infarction, coronary heart diseases, inflammation, increased formation of collagen, fibrosis such as cardiac or myocardiac fibrosis and remodeling following hypertension and endothelial dysfunction, gynecomastia, osteoporosis, prostate cancer, endometriosis, uterine fibroids, dysfunctional uterine bleeding, endometrial hyperplasia, polycystic ovarian disease, infertility, fibrocystic breast disease, breast cancer and fibrocystic mastopathy. Finally, the present invention also provides a pharmaceutical composition.

  本发明提供了一种化合物I，其为醛固酮合成酶和芳香化酶的抑制剂，因此可用于治疗由醛固酮合成酶或芳香化酶介导的疾病或疾病。因此，化合物I可用于治疗低钾血症、高血压、充血性心力衰竭、心房颤动、肾衰竭，特别是慢性肾衰竭、再狭窄、动脉粥样硬化、X综合症、肥胖症、肾病、心肌梗死后、冠心病、炎症、胶原形成增加、纤维化如心脏或心肌纤维化以及高血压和内皮功能障碍后的重塑、男性乳腺增生、骨质疏松症、前列腺癌、子宫内膜异位症、子宫肌瘤、功能性子宫出血、子宫内膜增生、多囊卵巢综合症、不孕症、纤维囊性乳房病、乳腺癌和纤维囊性乳房病。最后，本发明还提供了一种制药组合物。
• Condensed imidazolo derivatives for the inhibition of aromatase
  申请人：Novartis AG

  公开号：EP2256118A1

  公开（公告）日：2010-12-01

  The present invention relates to novel imidazole derivatives that are used as aromatase inhibitors, as well as for treatment of a disorder or disease mediated by aromatase.

  本发明涉及可用作芳香化酶抑制剂以及用于治疗由芳香化酶介导的紊乱或疾病的新型咪唑衍生物。
• CONDENSED IMIDAZOLO DERIVATIVES FOR THE INHIBITION OF ALDOSTERONE SYNTHASE AND AROMATASE
  申请人：Novartis AG

  公开号：EP1919916A1

  公开（公告）日：2008-05-14
• Condensed imidazolo derivatives for the inhibition of aromatase and the treatment of aldosterone related diseases
  申请人：Novartis AG

  公开号：EP2256118B1

  公开（公告）日：2014-10-29