3-bromo-4-chloro-5-fluorophenol | 1805015-17-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: 3-bromo-4-chloro-5-fluorophenol
• CAS: 1805015-17-1
• 化学式: C₆H₃BrClFO
• 分子量: 225.445
• InChiKey: JLHNWRBZQQAWRC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  20.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-bromo-4-chloro-5-fluorophenol 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 50.0h， 生成 2-(3-bromo-4-chloro-5-fluorophenoxy)acetic acid
  参考文献：
  名称：

  [EN] MODULATORS OF THE INTEGRATED STRESS PATHWAY
  [FR] MODULATEURS DE LA VOIE DE RÉPONSE INTÉGRÉE AU STRESS

  摘要：

  本文提供了一些化合物、组合物和方法，用于调节综合应激反应（ISR）和治疗相关疾病、疾患和病况。

  公开号：

  WO2022094244A1

文献信息

• [EN] NEW PYRROLIDINE-2-CARBOXYLIC ACID DERIVATIVES FOR TREATING PAIN AND PAIN RELATED CONDITIONS<br/>[FR] NOUVEAUX DÉRIVÉS D'ACIDE PYRROLIDINE-2-CARBOXYLIQUE POUR LE TRAITEMENT DE LA DOULEUR ET D'ÉTATS PATHOLOGIQUES ASSOCIÉS À LA DOULEUR
  申请人：ESTEVE PHARMACEUTICALS SA

  公开号：WO2020120539A1

  公开（公告）日：2020-06-18

  The present invention relates to new compounds that show pharmacological dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels, and the µ-opiod receptor (MOR or mu-opioid). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments (formula (I)).

  本发明涉及显示对电压门控钙通道（VGCC）的α2δ亚基，特别是电压门控钙通道的α2δ-1亚基，以及µ-阿片受体（MOR或μ-阿片）具有药理双重活性的新化合物。该发明还涉及所述化合物的制备过程，以及包含它们的组合物，以及它们作为药物的用途（公式（I））。
• Towards multitargeted ligands as pain therapeutics: Dual ligands of the Ca_vα2δ‐1 subunit of voltage‐gated calcium channel and the μ‐opioid receptor
  作者：Anita Wegert、Menno Monnee、Wouter de Graaf、Frank van Holst、Giovanni Bolcato、José Luis Díaz、Albert Dordal、Enrique Portillo‐Salido、Raquel F. Reinoso、Sandra Yeste、Antoni Torrens、Carmen Almansa

  DOI：10.1002/cmdc.202300473

  日期：——

  The synthesis and pharmacological activity of a new series of dual ligands combining activities towards the α2δ‐1 subunit of voltage‐gated calcium channels (Ca_vα2δ‐1) and the μ‐opioid receptor (MOR) as novel pain therapeutics are reported. A careful exploration of the pharmacophores related to both targets, which in principle had few common characteristics, led to the design of novel compounds exhibiting both activities. The construction of the dual ligands started from published Ca_vα2δ‐1 ligands, onto which MOR ligand pharmacophoric elements were added. This exercise led to new amino‐acidic substances with good affinities on both targets as well as good metabolic and physicochemical profiles and low potential for drug‐drug interactions. A representative compound, (2S,4S)‐4‐(4‐chloro‐3‐(((cis)‐4‐(dimethylamino)‐4‐phenylcyclohexyl)methyl)‐5‐fluorophenoxy)pyrrolidine‐2‐carboxylic acid, displayed promising analgesic activities in several in vivo pain models as well as a reduced side‐effect profile in relation to morphine.

  摘要 报告了一系列新的双重配体的合成和药理活性，这些配体对电压门控钙通道（Cavα2δ-1）的α2δ-1亚基和μ-阿片受体（MOR）具有双重活性，可作为新型疼痛治疗药物。这两个靶点原则上几乎没有共同特征，通过对与之相关的药理作用的仔细探索，设计出了同时具有这两种活性的新型化合物。双配体的构建始于已发表的 Cavα2δ-1 配体，并在其上添加了 MOR 配体药效元素。通过这项工作，我们获得了对两个靶点都具有良好亲和力、代谢和理化特性良好、药物间相互作用可能性低的新型氨基酸物质。一个具有代表性的化合物是 (2S,4S)-4-(4-氯-3-(((顺式)-4-(二甲基氨基)-4-苯基环己基)甲基)-5-氟苯氧基)吡咯烷-2-羧酸，它在多个体内疼痛模型中显示出良好的镇痛活性，而且与吗啡相比，副作用更小。
• ACYLAMINO BRIDGED HETEROCYCLIC COMPOUND, AND COMPOSITION AND APPLICATION THEREOF
  申请人：Beijing Scitech-MQ Pharmaceuticals Limited

  公开号：EP3901147A1

  公开（公告）日：2021-10-27

  Provided are an acylamino bridged heterocyclic compound of formula (I) or a pharmaceutically acceptable salt, an isomer, a solvate, a crystal, or a prodrug thereof, and a pharmaceutical composition comprising the compound, and an application of the compound or composition in drug preparation. The compound and the pharmaceutically acceptable salt, the isomer, the solvate, the crystal, or the prodrug thereof and the like can be used for treatment or prevention of autoimmune diseases, tumors, and neurodegenerative diseases related to receptor-interacting protein kinase-1 (RIPK1).

  本发明提供了一种式(I)的酰氨基桥杂环化合物或其药学上可接受的盐、异构体、溶解物、晶体或原药，以及包含该化合物的药物组合物，以及该化合物或组合物在药物制剂中的应用。 该化合物及其药学上可接受的盐、异构体、溶物、晶体或原药等可用于治疗或预防与受体相互作用蛋白激酶-1（RIPK1）有关的自身免疫性疾病、肿瘤和神经退行性疾病。