2-(1-pyrryl)benzofuran | 1613031-37-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: 2-(1-pyrryl)benzofuran
• 英文别名: 1-(1-Benzofuran-2-yl)pyrrole
• CAS: 1613031-37-0
• 化学式: C₁₂H₉NO
• 分子量: 183.21
• InChiKey: XOIBHGWNXBQIJK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  18.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  水杨醛 在 potassium phosphate 、 copper(l) iodide 、 1,10-菲罗啉 、 三苯基膦 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 26.25h， 生成 2-(1-pyrryl)benzofuran
  参考文献：
  名称：

  铜催化邻羟基宝石-(二溴乙烯基)苯和N-杂芳烃合成1-(2-苯并呋喃基)-N-杂芳烃

  摘要：

  一种有效的合成 1-(2-苯并呋喃基)-N-杂芳烃的方法是在铜催化的串联反应条件下由邻羟基宝石-(二溴乙烯基)苯和 N-杂芳烃开发的。该方法在制备各种 1-(2-苯并呋喃基)-N-杂芳烃时表现出广泛的底物范围和高产率。此外，1-(2-苯并呋喃基)-N-杂芳烃也被应用于在钯催化脱氢偶联条件下合成多环苯并呋喃-吲哚-吡啶支架。总体而言，目前的串联方法是通用的，综合优势，避免空气敏感试剂。

  DOI：

  10.1039/d1ob01765a

文献信息

• Synthesis of C,N′-linked bis-heterocycles using a deprotometalation–iodination–N-arylation sequence and evaluation of their antiproliferative activity in melanoma cells
  作者：Madani Hedidi、Ghenia Bentabed-Ababsa、Aïcha Derdour、Thierry Roisnel、Vincent Dorcet、Floris Chevallier、Laurent Picot、Valérie Thiéry、Florence Mongin

  DOI：10.1016/j.bmc.2014.04.028

  日期：2014.7

  crude iodides were involved in the N-arylation of pyrrole, indole, carbazole, pyrazole, indazole, imidazole and benzimidazole in the presence of Cu (0.2 equiv) and Cs2CO3 (2 equiv), and using acetonitrile as solvent (no other ligand) to provide after 24 h reflux the expected N-arylated azoles in yields ranging from 33% to 81%. Using benzotriazole also led to N-arylation products, but in lower 34%, 39%

  苯并噻吩，苯并呋喃，苯并噻唑和苯并恶唑是使用由ZnCl 2 ·TMEDA（TMEDA =  N，N，N '，N'-四甲基乙二胺，1当量）和2,2,6,6-四甲基哌啶锂制备的锂-锌组合脱金属金属盐的。（LiTMP，3当量）。随后使用碘作为亲电试剂拦截2-金属化衍生物，碘化物的收率分别为81％，82％，67％和42％。与使用ZnCl 2获得的产率相比，这些产率更高（提高了10％）·TMEDA（0.5当量）和LiTMP（1.5当量），但苯并恶唑（少10％）的情况除外。在Cu（0.2当量）和Cs 2 CO 3存在下，粗碘化物参与吡咯，吲哚，咔唑，吡唑，吲唑，咪唑和苯并咪唑的N-芳基化反应（2当量），并使用乙腈作为溶剂（无其他配体），在回流24小时后提供预期的N-芳基化吡咯，产率为33％至81％。使用苯并三唑还可以产生N-芳基化产物，但产率分别较低，分别为34％，39％，36％和6％。对该唑的进一步研究证明了2
• [EN] BICYCLOHETEROARYL-HETEROARYL-BENZOIC ACID COMPOUNDS AS RETINOIC ACID RECEPTOR BETA (RARβ) AGONISTS<br/>[FR] COMPOSÉS DE TYPE ACIDE BICYCLOHÉTÉROARYL-HÉTÉROARYL-BENZOÏQUE UTILISÉS COMME AGONISTES DE RÉCEPTEURS BÊTA DE L'ACIDE RÉTINOÏQUE (RARΒ)
  申请人：KING S COLLEGE LONDON

  公开号：WO2016097004A1

  公开（公告）日：2016-06-23

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds of the following formula (for convenience, collectively referred to herein as "BHBA compounds"), which, inter alia, are (selective) retinoic acid receptor beta (RARβ) (e.g., RARβ2) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARβ (e.g., RARβ2), to cause or promote neurite development, neurite outgrowth, and/or neurite regeneration, and in the treatment of diseases and conditions that are mediated by RARβ (e.g., RARβ2), that are ameliorated by the activation of RARβ (e.g., RARβ2), etc., including, e.g., neurological injuries such as spinal cord injuries.

  本发明涉及治疗化合物领域，更具体地涉及以下公式的某些双环杂环芳基-杂环芳基-苯甲酸化合物（为方便起见，统称为“BHBA化合物”），它们是（选择性）视黄酸受体β（RARβ）（例如，RARβ2）激动剂。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物在体内外（选择性）激活RARβ（例如，RARβ2），导致或促进神经突起发育、神经突起和/或神经再生，以及治疗由RARβ（例如，RARβ2）介导的疾病和症状，通过RARβ（例如，RARβ2）激活而得到改善等，包括神经损伤如脊髓损伤。
• [EN] CRYSTALLINE FORMS OF 4-(5-(4,7-DIMETHYLBENZOFURAN-2-YL)-1,2,4-OXADIAZOL-3-YL)BENZOIC ACID AND PROCESSES FOR THEIR PREPARATION<br/>[FR] FORMES CRISTALLINES DE L'ACIDE 4-(5-(4,7-DIMÉTHYLBENZOFURAN-2-YL)-1,2,4-OXADIAZOL-3-YL) BENZOÏQUE ET LEURS PROCÉDÉS DE PRÉPARATION
  申请人：KING'S COLLEGE LONDON

  公开号：WO2017220446A1

  公开（公告）日：2017-12-28

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to crystalline forms of 4-(5-(4,7-dimethylbenzofuran-2-yl)-1,2,4-oxadiazol-3-yl)benzoic acid (referred to herein as "BHBA-001"), which, inter alia, is a (selective) retinoic acid receptor beta (RARβ) (e.g., RARβ2) agonist. The present invention also pertains to pharmaceutical compositions comprising such crystalline forms, and the use of such crystalline forms and compositions, both in vitro and in vivo, to (selectively) activate RARβ (e.g., RARβ2), to cause or promote neurite development, neurite outgrowth, and/or neurite regeneration, and in the treatment of diseases and conditions that are mediated by RARβ (e.g., RARβ2), that are ameliorated by the activation of RARβ (e.g., RARβ2), etc., including, e.g., neurological injuries such as spinal cord injuries.

  本发明一般涉及治疗化合物领域，更具体地涉及4-(5-(4,7-二甲基苯并呋喃-2-基)-1,2,4-噁二唑-3-基)苯甲酸的结晶形式（以下简称为"BHBA-001"），该化合物是一种（选择性）视黄酸受体β（RARβ）（例如RARβ2）激动剂。本发明还涉及包含这种结晶形式的药物组合物，以及利用这种结晶形式和组合物在体内外（选择性地）激活RARβ（例如RARβ2），促进神经元发育、神经元生长和/或神经元再生，以及治疗通过RARβ（例如RARβ2）介导的疾病和症状，通过激活RARβ（例如RARβ2）得到改善等。这些疾病和症状包括神经系统损伤如脊髓损伤。
• Bicycloheteroaryl-heteroaryl-benzoic acid compounds as retinoic acid receptor beta (RARβ) agonists
  申请人：King's College London

  公开号：US10385044B2

  公开（公告）日：2019-08-20

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain bicycloheteroaryl-heteroaryl-benzoic acid compounds of the following formula (for convenience, collectively referred to herein as “BHBA compounds”), which, inter alia, are (selective) retinoic acid receptor beta (RARβ) (e.g., RARβ2) agonists. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to (selectively) activate RARβ (e.g., RARPβ2), to cause or promote neurite development, neurite outgrowth, and/or neurite regeneration, and in the treatment of diseases and conditions that are mediated by RARβ (e.g., RARβ2), that are ameliorated by the activation of RARβ (e.g., RARβ2), etc., including, e.g., neurological injuries such as spinal cord injuries.

  本发明一般涉及治疗化合物领域，更具体地说，涉及下式的某些双环杂芳基-杂芳基苯甲酸化合物（为方便起见，本文统称为 "BHBA化合物"），它们是（选择性）视黄酸受体β（RARβ）（如RARβ2）激动剂。本发明还涉及包含此类化合物的药物组合物，以及在体外和体内使用此类化合物和组合物来（选择性地）激活 RARβ（如 RARPβ2）、RARPβ2），引起或促进神经元发育、神经元生长和/或神经元再生，以及治疗由 RARβ（如 RARβ2）介导的、通过激活 RARβ（如 RARβ2）而改善的疾病和病症等，包括神经损伤，如脊髓损伤。
• Crystalline forms of 4-(5-(4,7-dimethylbenzofuran-2-yl)-l,2,4-oxadiazol-3-yl)benzoic acid and processes for their preparation
  申请人：King's College London

  公开号：US10870644B2

  公开（公告）日：2020-12-22

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to crystalline forms of 4-(5-(4,7-dimethylbenzofuran-2-yl)-1,2,4-oxadiazol-3-yl)benzoic acid (referred to herein as “BHBA-001”), which, inter alia, is a (selective) retinoic acid receptor beta (RARβ) (e.g., RARβ2) agonist. The present invention also pertains to pharmaceutical compositions comprising such crystalline forms, and the use of such crystalline forms and compositions, both in vitro and in vivo, to (selectively) activate RARβ (e.g., RARβ2), to cause or promote neurite development, neurite outgrowth, and/or neurite regeneration, and in the treatment of diseases and conditions that are mediated by RARβ(e.g., RARβ2), that are ameliorated by the activation of RARβ (e.g., RARβ2), etc., including, e.g., neurological injuries such as spinal cord injuries.

  本发明一般涉及治疗化合物领域，更具体地说，涉及 4-(5-(4,7-二甲基苯并呋喃-2-基)-1,2,4-恶二唑-3-基)苯甲酸的结晶形式（本文称为 "BHBA-001"），它是一种（选择性）维甲酸受体 beta（RARβ）（例如 RARβ2）激动剂。本发明还涉及包含这种结晶形式的药物组合物，以及在体外和体内使用这种结晶形式和组合物来（选择性地）激活 RARβ（如 RARβ2）、RARβ2），引起或促进神经元发育、神经元生长和/或神经元再生，以及治疗由 RARβ（如 RARβ2）介导的、通过激活 RARβ（如 RARβ2）而改善的疾病和病症等，包括神经损伤，如脊髓损伤。