2-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-indole-6-carbonitrile | 1026694-04-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 2-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-indole-6-carbonitrile
• 英文别名: 2-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-(trifluoromethyl)pentyl]-1H-indole-6-carbonitrile
• CAS: 1026694-04-1
• 化学式: C₂₃H₂₂F₄N₂O₂
• 分子量: 434.433
• InChiKey: KJUOEYJRZUJJLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  69
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-羟基-3-硝基苯甲腈 在 copper(l) iodide 、 二氯双(三邻甲苯膦)合钯(II) 、 铁粉 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 2.75h， 生成 2-[4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentyl]-1H-indole-6-carbonitrile
  参考文献：
  名称：

  Non-steroidal dissociated glucocorticoid agonists: indoles as A-ring mimetics and function-regulating pharmacophores

  摘要：

  We report a SAR of non-steroidal glucocorticoid mimetics that utilize indoles as A-ring mimetics. Detailed SAR is discussed with a focus on improving PR and MR selectivity, GR agonism, and in vitro dissociation profile. SAR analysis led to compound (R)-33 which showed high PR and MR selectivity, potent agonist activity, and reduced transactivation activity in the MMTV and aromatase assays. The compound is equipotent to prednisolone in the LPS-TNF model of inflammation. In mouse CIA, at 30 mg/kg compound (R)-33 inhibited disease progression with an efficacy similar to the 3 mg/kg dose of prednisolone. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.018

文献信息

• [EN] 1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO<br/>[FR] DERIVES DE 1,1,1-TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO-2,3-C PYRIDIN-2-YLMETHYL)PENTAN-2-OLE ET COMPOSES ASSOCIES EN TANT QUE LIGANDS DE GLUCOCORTICOIDES POUR LE TRAITEMENT DE MALADIES INFLAMMATOIRES ET DE DIABETE
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2005030213A1

  公开（公告）日：2005-04-07

  Compounds of Formula (IA), IB), IC), and (ID) wherein R1, R2, R3, R4, R5, and R6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  式(I A)、(IB)、(IC)和(ID)的化合物，其中R1、R2、R3、R4、R5和R6分别如本文所定义的式(I A)、(IB)、(IC)和(ID)，或其互变异构体、前药、溶剂化合物或盐；含有这些化合物的药物组合物，以及利用这些化合物调节糖皮质激素受体功能的方法，以及利用这些化合物治疗由糖皮质激素受体功能介导或以炎症、过敏或增殖过程为特征的疾病状态或病情的方法。
• Glucocorticoid mimetics, methods of making them, pharmaceutical compositions and uses thereof
  申请人：Bekkali Younes

  公开号：US20050176706A1

  公开（公告）日：2005-08-11

  Compounds of Formula (IA), (IB), (IC), and (ID) wherein R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are as respectively defined herein for Formula (IA), (IB), (IC), and (ID), or a tautomer, prodrug, solvate, or salt thereof; pharmaceutical compositions containing such compounds, and methods of modulating the glucocorticoid receptor function and methods of treating disease-states or conditions mediated by the glucocorticoid receptor function or characterized by inflammatory, allergic, or proliferative processes in a patient using these compounds.

  化合物的公式为（IA），（IB），（IC）和（ID），其中R1，R2，R3，R4，R5和R6分别定义为公式（IA），（IB），（IC）和（ID）中所述，或其互变异构体，前药，溶剂化物或盐; 包含这些化合物的药物组合物以及使用这些化合物调节糖皮质激素受体功能的方法和治疗由糖皮质激素受体功能介导或以炎症，过敏或增生过程为特征的疾病状态或病情的方法。
• COMPOSITIONS AND METHODS FOR TREATING, CONTROLLING, REDUCING, OR AMELIORATING INFLAMMATORY PAIN
  申请人：Ward Keith W.

  公开号：US20120316199A1

  公开（公告）日：2012-12-13

  A composition for treating, controlling, reducing, or ameliorating inflammatory pain comprises a dissociated glucocorticoid receptor agonist (“DIGRA”), a prodrug thereof, a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable ester thereof. The composition can comprise an additional anti-inflammatory agent and can be formulated for topical application, injection, or implantation. It may be used in a method of managing post-surgical ocular pain such that it has lower risk of eliciting adverse side effects seen with other therapeutic agents.

  用于治疗、控制、减轻或改善炎症性疼痛的组合物包括解离型糖皮质激素受体激动剂（“DIGRA”）、其前药、其药学上可接受的盐或其药学上可接受的酯。该组合物可以包含额外的抗炎药物，并可制成局部应用、注射或植入剂。它可以用于管理术后眼部疼痛的方法，从而降低与其他治疗剂产生的不良副作用风险。
• Compositions and methods for treating, controlling, reducing, or ameliorating infections and sequelae thereof
  申请人：BAUSCH & LOMB INCORPORATED

  公开号：EP2364707A2

  公开（公告）日：2011-09-14

  A composition for treating, controlling, reducing, ameliorating, or alleviating infections and their inflammatory sequelae comprises a dissociated glucocorticoid receptor agonist ('DIGRA') and an anti-infective agent, such as an antibacterial, antiviral, antifungal, antiprotozoal agent, or a combination thereof. The composition can be formulated for topical application, injection, or implantation.

  一种用于治疗、控制、减少、改善或减轻感染及其炎症后遗症的组合物包含一种解离糖皮质激素受体激动剂（"DIGRA"）和一种抗感染剂，如抗菌剂、抗病毒剂、抗真菌剂、抗原虫剂或其组合。该组合物可配制成外用、注射或植入剂。
• 1,1,1- TRIFLUORO-4-PHENYL-4-METHYL-2-(1H-PYRROLO¬2,3-C|PYRIDIN-2-YLMETHYL)PENTAN-2-OL DERIVATIVES AND RELATED COMPOUNDS AS GLUCOCORTICOID LIGANDS FOR THE TREATMENT OF INFLAMMATORY DISEASES AND DIABETES
  申请人：Boehringer Ingelheim Pharmaceuticals Inc.

  公开号：EP1673088A1

  公开（公告）日：2006-06-28