2-fluoro-4-(1H-pyrrol-1-yl)phenol | 1339084-93-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-fluoro-4-(1H-pyrrol-1-yl)phenol
• 英文别名: 2-fluoro-4-pyrrol-1-ylphenol
• CAS: 1339084-93-3
• 化学式: C₁₀H₈FNO
• 分子量: 177.178
• InChiKey: KKMFTFGRVDYTCN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-fluoro-4-(1H-pyrrol-1-yl)phenol 在 aluminum (III) chloride 、 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 1,2-二氯乙烷 为溶剂， 反应 48.25h， 生成 [1-(3-fluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone
  参考文献：
  名称：

  Decreasing acidity in a series of aldose reductase inhibitors: 2-Fluoro-4-(1H-pyrrol-1-yl)phenol as a scaffold for improved membrane permeation

  摘要：

  Targeting long-term diabetic complications, as well as inflammatory pathologies, aldose reductase inhibitors (ARIs) have been gaining attention over the years. In the present work, in order to address the poor membrane permeation of previously reported ARIs, derivatives of N-phenylpyrrole, bearing groups with putative pK(a) >= 7.4, were synthesized and evaluated for aldose reductase inhibitory activity. The 2-fluorophenol group proved the most promising moiety, and further modifications were explored. The most active compound (31), identified as a submicromolar inhibitor (IC50 = 0.443 mu M), was also selective against the homologous enzyme aldehyde reductase. Cross-docking revealed that 31 displays a peculiar interaction network that may be responsible for high affinity. Physicochemical profiling of 31 showed a pK(a) of 7.64, rendering it less than 50% ionized in the physiological pH range, with potentially favorable membrane permeation. The latter was supported from the successful inhibition of sorbitol formation in rat lenses and the ability to permeate rat jejunum. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.02.016
• 作为产物：
  描述：

  2-氟-4-硝基苯酚 在 盐酸 、 palladium 10% on activated carbon 、 烟酰胺 、 环己烯 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 8.0h， 生成 2-fluoro-4-(1H-pyrrol-1-yl)phenol
  参考文献：
  名称：

  Clauson–Kaas-Type Synthesis of Pyrrolyl-phenols, from the Hydrochlorides of Aminophenols, in the Presence of Nicotinamide

  摘要：

  A facile Clauson-Kaas-type pyrrolyl-phenol synthesis has been achieved in the presence of nicotinamide, which is inexpensive and nontoxic. The starting material is aminophenol hydrochloride. This is advantageous in certain cases because it is the only isolatable form of the corresponding aminophenol. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource: Full experimental and spectral details.]

  DOI：

  10.1080/00397911.2012.753460

文献信息

• [EN] MODULATORS OF THE GPR119 RECEPTOR AND THE TREATMENT OF DISORDERS RELATED THERETO<br/>[FR] MODULATEURS DU RÉCEPTEUR GPR119 ET TRAITEMENT DE TROUBLES LIÉS À CELUI-CI
  申请人：ARENA PHARM INC

  公开号：WO2012145361A1

  公开（公告）日：2012-10-26

  The present invention relates to compounds of Formula I and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of, for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及式I的化合物及其药学上可接受的盐、溶剂合物和水合物，这些化合物可作为单一药物代理或与一个或多个额外的药物代理结合使用，例如DPP-IV抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、美格列奈、噻唑烷二酮或抗糖尿病肽类似物，用于治疗例如从以下选择的疾病中选择的疾病：GPR119受体相关疾病；通过增加血液胰高血糖素水平改善的疾病；低骨量症状；神经系统疾病；与代谢相关的疾病；2型糖尿病；肥胖症；以及相关并发症。
• Modulators Of The GPR119 Receptor And The Treatment Of Disorders Related Thereto
  申请人：Jones Robert M.

  公开号：US20140066369A1

  公开（公告）日：2014-03-06

  The present invention relates to compounds of Formula I and pharmaceutically acceptable salts, solvates, and hydrates thereof, that are useful as single pharmaceutical agents or in combination with one or more additional pharmaceutical agents, such as, a DPP-IV inhibitor, a biguanide, an alpha-glucosidase inhibitor, an insulin analogue, a sulfonylurea, an SGLT2 inhibitor, a meglitinide, a thiazolidinedione, or an anti-diabetic peptide analogue, in the treatment of for example, a disorder selected from: a GPR119-receptor-related disorder; a condition ameliorated by increasing a blood incretin level; a condition characterized by low bone mass; a neurological disorder; a metabolic-related disorder; type 2 diabetes; obesity; and complications related thereto.

  本发明涉及式I化合物及其药学上可接受的盐、溶剂和水合物，它们可作为单一药物或与一个或多个其他药物联合使用，例如DPP-IV抑制剂、双胍类药物、α-葡萄糖苷酶抑制剂、胰岛素类似物、磺脲类药物、SGLT2抑制剂、噻唑烷二酮类药物或抗糖尿病肽类似物，用于治疗选择性疾病，例如GPR119受体相关疾病、通过增加血液肠促素水平改善的病症、低骨量的病症、神经系统疾病、代谢相关疾病、2型糖尿病、肥胖及其相关并发症。
• Decreasing acidity in a series of aldose reductase inhibitors: 2-Fluoro-4-(1H-pyrrol-1-yl)phenol as a scaffold for improved membrane permeation
  作者：Maria Chatzopoulou、Alexandros Patsilinakos、Theodosia Vallianatou、Marta Soltesova Prnova、Simon Žakelj、Rino Ragno、Milan Stefek、Albin Kristl、Anna Tsantili-Kakoulidou、Vassilis J. Demopoulos

  DOI：10.1016/j.bmc.2014.02.016

  日期：2014.4

  Targeting long-term diabetic complications, as well as inflammatory pathologies, aldose reductase inhibitors (ARIs) have been gaining attention over the years. In the present work, in order to address the poor membrane permeation of previously reported ARIs, derivatives of N-phenylpyrrole, bearing groups with putative pK(a) >= 7.4, were synthesized and evaluated for aldose reductase inhibitory activity. The 2-fluorophenol group proved the most promising moiety, and further modifications were explored. The most active compound (31), identified as a submicromolar inhibitor (IC50 = 0.443 mu M), was also selective against the homologous enzyme aldehyde reductase. Cross-docking revealed that 31 displays a peculiar interaction network that may be responsible for high affinity. Physicochemical profiling of 31 showed a pK(a) of 7.64, rendering it less than 50% ionized in the physiological pH range, with potentially favorable membrane permeation. The latter was supported from the successful inhibition of sorbitol formation in rat lenses and the ability to permeate rat jejunum. (C) 2014 Elsevier Ltd. All rights reserved.
• Clauson–Kaas-Type Synthesis of Pyrrolyl-phenols, from the Hydrochlorides of Aminophenols, in the Presence of Nicotinamide
  作者：Maria Chatzopoulou、Eleni Kotsampasakou、Vassilis J. Demopoulos

  DOI：10.1080/00397911.2012.753460

  日期：2013.11.2

  A facile Clauson-Kaas-type pyrrolyl-phenol synthesis has been achieved in the presence of nicotinamide, which is inexpensive and nontoxic. The starting material is aminophenol hydrochloride. This is advantageous in certain cases because it is the only isolatable form of the corresponding aminophenol. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource: Full experimental and spectral details.]