methyl 2-(4-cyano-2-fluorophenyl)-2-(5-(2-((methylsulfonyl)oxy)ethyl)-1H-imidazol-1-yl)acetate | 1472004-21-9

• 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: methyl 2-(4-cyano-2-fluorophenyl)-2-(5-(2-((methylsulfonyl)oxy)ethyl)-1H-imidazol-1-yl)acetate
• 英文别名: Methyl 2-(4-cyano-2-fluorophenyl)-2-[5-(2-methylsulfonyloxyethyl)imidazol-1-yl]acetate
• CAS: 1472004-21-9
• 化学式: C₁₆H₁₆FN₃O₅S
• 分子量: 381.385
• InChiKey: FWBMMKJQFCYQQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  26.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  111.28
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-cyano-2-fluorophenyl)-2-(5-(2-((methylsulfonyl)oxy)ethyl)-1H-imidazol-1-yl)acetate 在 potassium carbonate 、 三乙胺 、 sodium iodide 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 反应 36.5h， 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
• 作为产物：
  描述：

  methyl 2-(5-(2-((tert-butyldimethylsilyl)oxy)ethyl)-1H-imidazol-1-yl)-2-(4-cyano-2-fluorophenyl)acetate 在 盐酸 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 methyl 2-(4-cyano-2-fluorophenyl)-2-(5-(2-((methylsulfonyl)oxy)ethyl)-1H-imidazol-1-yl)acetate
  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

• [EN] PROCESS FOR THE PRODUCTION OF CONDENSED IMIDAZOLO DERIVATIVES<br/>[FR] PROCÉDÉ DE PRODUCTION DE DÉRIVÉS D'IMIDAZOLES CONDENSÉS
  申请人：NOVARTIS AG

  公开号：WO2016120821A1

  公开（公告）日：2016-08-04

  The present invention relates to a process for providing the compound of formula I, comprising the step of reacting a compound of formula VII with a base in the presence of an alkaline- or alkaline earth metal salt (MX), wherein LG is a leaving group. The presence of an alkaline- or alkaline earth metal salt was surprisingly found to render said reaction highly reliable in terms of the yield and purity of the compound of formula I obtained. In a further aspect, the present invention relates to the compound of formula I, having less than an amount of 1.50% or less than an amount of 1.25% or less than an amount of 1.00% or less than an amount of 0.75% or less than an amount of 0.50% or less than an amount of 0.25% or less than an amount of 0.10% of the compound of formula VIII.

  本发明涉及一种提供式I化合物的方法，包括在碱性或碱土金属盐（MX）存在下，将式VII化合物与碱反应，其中LG是离去基团。惊人地发现，碱性或碱土金属盐的存在可以使得所得到的式I化合物的产率和纯度高度可靠。在另一个方面，本发明涉及式I化合物，其含有少于1.50％或少于1.25％或少于1.00％或少于0.75％或少于0.50％或少于0.25％或少于0.10％的式VIII化合物。
• Process for the production of condensed imidazolo derivatives
  申请人：Novartis AG

  公开号：US10556869B2

  公开（公告）日：2020-02-11

  The present invention relates to a process for providing the compound of formula I, comprising the step of reacting a compound of formula VII with a base in the presence of an alkaline- or alkaline earth metal salt (MX), wherein LG is a leaving group. The presence of an alkaline- or alkaline earth metal salt was surprisingly found to render said reaction highly reliable in terms of the yield and purity of the compound of formula I obtained. In a further aspect, the present invention relates to the compound of formula I, having less than an amount of 1.50% or less than an amount of 1.25% or less than an amount of 1.00% or less than an amount of 0.75% or less than an amount of 0.50% or less than an amount of 0.25% or less than an amount of 0.10% of the compound of formula VIII.

  本发明涉及一种提供式 I 化合物的工艺，包括在碱或碱土金属盐 (MX) 存在下使式 VII 化合物与碱反应的步骤，其中 LG 为离去基团。令人惊讶的是，碱金属或碱土金属盐的存在使所述反应在所获得的式 I 化合物的产率和纯度方面具有高度可靠性。在另一个方面，本发明涉及式 I 化合物，其式 VIII 化合物的含量小于 1.50%或小于 1.25%或小于 1.00%或小于 0.75%或小于 0.50%或小于 0.25%或小于 0.10%。
• [EN] 3-FLUORO-BENZONITRILE INHIBITORS OF 11-BETA-HYDROXYLASE<br/>[FR] INHIBITEURS 3-FLUORO-BENZONITRILES DE LA 11-BÊTA-HYDROXYLASE
  申请人：AUSPEX PHARMACEUTICALS INC

  公开号：WO2016109361A3

  公开（公告）日：2016-09-29
• ACS Med. Chem. Lett. 2013, 4, 1203-1207
  作者：

  DOI：——

  日期：——
• PROCESS FOR THE PRODUCTION OF CONDENSED IMIDAZOLO DERIVATIVES
  申请人：Recordati AG

  公开号：EP3250555B1

  公开（公告）日：2021-03-03