2,5-dichloro-4-hydroxybenzaldehyde | 27164-10-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,5-dichloro-4-hydroxybenzaldehyde
• 英文别名: 4-hydroxy-3,6-dichlorobenzaldehyde；Dichloro-2,5-hydroxy-4-benzaldehyd；4-Hydroxy-3,5-dichlor-benzaldehyd
• CAS: 27164-10-9
• 化学式: C₇H₄Cl₂O₂
• mdl: MFCD06656940
• 分子量: 191.014
• InChiKey: BUJHRHRKNMSZAW-UHFFFAOYSA-N

物化性质

• 保留指数：
  1435;1445;1449;1449;1449;1459;1464;1449

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,5-dichloro-4-hydroxybenzaldehyde 在 哌啶 、 吡啶 、 sodium hydroxide 、 草酰氯 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 甲苯 、 乙腈 、 苯 为溶剂， 反应 7.25h， 生成 1-{3-[2,5-Dichloro-4-(2-methoxy-phenylsulfanyl)-phenyl]-acryloyl}-piperidine-4-carboxylic acid
  参考文献：
  名称：

  Discovery of Novel p-Arylthio Cinnamides as Antagonists of Leukocyte Function-Associated Antigen-1/Intercellular Adhesion Molecule-1 Interaction. 4. Structure−Activity Relationship of Substituents on the Benzene Ring of the Cinnamide

  摘要：

  We have shown that p-arylthio cinnamides can inhibit the interaction of LFA-1 and ICAM-1, which is involved in cell adhesion and the inflammatory process. We now show that 2,3-disubstitution on the aryl portion of the cinnamide results in enhanced activity over mono substitution on the ring. The best 2,3-substituents were chlorine and trifluoromethyl groups. Compounds 39 and 40 which contain two CF3 groups have IC50 values of 0.5 and 0.1 nM, respectively, in inhibiting JY8 cells expressing LFA-1 on their surface, from adhering to ICAM-1. The structure-activity relationship (SAR) was examined using an NMR based model of the LFA-1 I domain/compound 31 complex. One of our compounds (38) was able to reduce cell migration in two different in vivo experiments.

  DOI：

  10.1021/jm0103108
• 作为产物：
  描述：

  2,5-二氯苯甲醚 在 四氯化钛 、 lithium chloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2,5-dichloro-4-hydroxybenzaldehyde
  参考文献：
  名称：

  G蛋白偶联的胆汁酸受体1（GPBAR1，TGR5）的肠限制噻唑烷激动剂的设计

  摘要：

  胃肠道中的胆汁酸信号和新陈代谢对全身性疾病具有广泛的影响。G蛋白偶联的胆汁酸受体1（GPBAR1，TGR5）是胆汁酸感测的主要效应器之一，已证明对代谢，炎症和增殖过程有影响。TGR5激动剂的药理作用受到全身靶标相关作用的限制，例如过多的胆囊填充和阻塞胆囊排空。但是，受肠道限制的TGR5激动剂有可能避免这些副作用，因此被开发成安全性可接受的药物。我们描述了一系列肠道受限的TGR5激动剂的发现和优化，这些激动剂在小鼠中引发了有效的反应，而胆囊相关的影响也最小。该系列包括12（TGR5 EC 50：人，143 nM；小鼠，1.2 nM），一种具有最小系统可用性的化合物，可能对2型糖尿病，非酒精性脂肪性肝炎或炎性肠病患者具有治疗价值。

  DOI：

  10.1021/acs.jmedchem.8b00308

文献信息

• [EN] NON-SYSTEMIC TGR5 AGONISTS<br/>[FR] AGONISTES DE TGR5 NON SYSTÉMIQUES
  申请人：ARDELYX INC

  公开号：WO2013096771A1

  公开（公告）日：2013-06-27

  Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.

  结构(I)的化合物，或其立体异构体、互变异构体、药学上可接受的盐或前药，其中R1、R2、R3、R4、R8、R9、R10、R11、R12、A1、A2、X、Y和Z如本文所定义。提供了这些化合物作为TGR5拮抗剂的用途，以及用于治疗各种适应症，包括II型糖尿病。
• Histamine-3 receptor antagonists
  申请人：Pfizer Inc.

  公开号：US07812040B2

  公开（公告）日：2010-10-12

  This invention is directed to a compound of the formula Ia or Ib, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I, a method of treatment of a disorder or condition that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), psychotic disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the GI tract, hyper and hypo motility and acidic secretion of the gastro-intestinal tract, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above.

  本发明涉及公式Ia或Ib的化合物，如本文所定义，或其药学上可接受的盐；含有公式I化合物的制药组合物；一种治疗通过拮抗组胺H3受体可治疗的紊乱或疾病的方法，该方法包括向需要该治疗的哺乳动物给予上述的公式I化合物；以及一种治疗从以下组中选择的紊乱或疾病的方法，该组包括抑郁症、情绪障碍、精神分裂症、焦虑症、阿尔茨海默病、注意力缺陷障碍（ADD）、注意力缺陷/多动障碍（ADHD）、精神障碍、睡眠障碍、肥胖症、头晕、癫痫、晕动病、呼吸系统疾病、过敏、过敏引起的气道反应、过敏性鼻炎、鼻塞、过敏性充血、充血、低血压、心血管疾病、胃肠道疾病、胃肠道高低运动和酸性分泌的方法，该方法包括向需要该治疗的哺乳动物给予上述的公式I化合物。
• NON-SYSTEMIC TGR5 AGONISTS
  申请人：Ardelyx, Inc.

  公开号：US20150148311A1

  公开（公告）日：2015-05-28

  Compounds having the following structure (I): or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R 1 , R 2 , R 3 , R 4 , R 8 , R 9 , R 10 , R 11 , R 12 , A 1 , A 2 , X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.

  具有以下结构（I）或其立体异构体，互变异构体，药学上可接受的盐或前药的化合物，其中R1、R2、R3、R4、R8、R9、R10、R11、R12、A1、A2、X、Y和Z如本文所定义。本文还提供了这种化合物作为TGR5拮抗剂和治疗各种症状，包括II型糖尿病的用途。
• HISTAMINE-3 RECEPTOR ANTAGONISTS
  申请人：Wager Travis T.

  公开号：US20090131433A1

  公开（公告）日：2009-05-21

  This invention is directed to a compound of the formula Ia or Ib, as defined herein, or a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing a compound of formula I, a method of treatment of a disorder or condition that may be treated by antagonizing histamine H3 receptors, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above, and a method of treatment of a disorder or condition selected from the group consisting of depression, mood disorders, schizophrenia, anxiety disorders, Alzheimer's disease, attention-deficit disorder (ADD), attention-deficit hyperactivity disorder (ADHD), psychotic disorders, sleep disorders, obesity, dizziness, epilepsy, motion sickness, respiratory diseases, allergy, allergy-induced airway responses, allergic rhinitis, nasal congestion, allergic congestion, congestion, hypotension, cardiovascular disease, diseases of the GI tract, hyper and hypo motility and acidic secretion of the gastro-intestinal tract, the method comprising administering to a mammal in need of such treatment a compound of formula I as described above.

  本发明涉及公式Ia或Ib的化合物，如本文所定义，或其药学上可接受的盐; 包含公式I化合物的制药组合物; 一种治疗通过拮抗组胺H3受体可以治疗的疾病或症状的方法，该方法包括向需要此类治疗的哺乳动物注射上述的公式I化合物; 以及一种治疗选择自抑郁症、情绪障碍、精神分裂症、焦虑症、阿尔茨海默病、注意力缺陷障碍（ADD）、注意力缺陷多动障碍（ADHD）、精神障碍、睡眠障碍、肥胖症、头晕、癫痫、晕动病、呼吸系统疾病、过敏、过敏引起的气道反应、过敏性鼻炎、鼻塞、过敏性充血、充血、低血压、心血管疾病、胃肠道疾病、胃肠道高低运动性和酸性分泌的方法，该方法包括向需要此类治疗的哺乳动物注射上述的公式I化合物。
• Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists
  申请人：Ardelyx, Inc.

  公开号：US10392413B2

  公开（公告）日：2019-08-27

  The invention relates to non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition especially during short bowel syndrome, and irritable bowel syndrome (IBS), and other TGR5 associated diseases and disorders, having the Formula: where R1, R2, R2′, R3, R4, X1, X2, X3, X4, Q, and n are described herein.

  本发明涉及可用于治疗化疗引起的腹泻、糖尿病、II 型糖尿病、妊娠糖尿病、空腹血糖受损、糖耐量受损、胰岛素抵抗、高血糖、肥胖、代谢综合征、溃疡性结肠炎、克罗恩病、肠外营养相关疾病，尤其是短肠综合征和肠易激综合征（IBS），以及其他与 TGR5 相关的疾病和失调的非系统性 TGR5 激动剂，其配方如下： 其中 R1、R2、R2′、R3、R4、X1、X2、X3、X4、Q 和 n 如本文所述。