4-[5-(4,7-dichloro-1-benzofuran-2-yl)-1H-pyrrol-2-yl]benzoic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-[5-(4,7-dichloro-1-benzofuran-2-yl)-1H-pyrrol-2-yl]benzoic acid
• 化学式: C₁₉H₁₁Cl₂NO₃
• 分子量: 372.207
• InChiKey: WEETWSJXNUQHMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2,5-二氯苯酚 在 乙酸铵 、 sodium hydroxide 、 正丁基锂 、 PPA 、 3-苄基羟乙基甲基噻唑氯化锂 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 7.25h， 生成 4-[5-(4,7-dichloro-1-benzofuran-2-yl)-1H-pyrrol-2-yl]benzoic acid
  参考文献：
  名称：

  Discovery of Novel and Potent Retinoic Acid Receptor α Agonists:  Syntheses and Evaluation of Benzofuranyl-pyrrole and Benzothiophenyl-pyrrole Derivatives

  摘要：

  In the course of our studies on retinoic acid receptor (RAR) agonists, we have designed and synthesized a series of benzofuran and benzothiophene derivatives. Some of these compounds (1a,b,e,f,j) markedly inhibited LPS-induced B-lymphocyte proliferation and exerted RAR alpha selectivity. One of them, 4-[5-(4,7-dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid (1b), when orally administered significantly inhibited mouse antibody production and delayed type hypersensitivity (DTH) responses from a dose of 0.1 mg/kg.

  DOI：

  10.1021/jm000098s

文献信息

• FUSED-RING CARBOXYLIC ACID DERIVATIVES
  申请人：Eisai Co., Ltd.

  公开号：EP0889032A1

  公开（公告）日：1999-01-07

  Fused-ring carboxylic acid derivatives represented by general formula (A) and pharmacologically acceptable salts thereof, which can provide medicines excellent in retinoic acid receptor agonist activities, wherein the symbolrepresents a single or double bond; and each of X, Y, Z, P, Q, U, V and W represents -O-, -S- or a group represented by formula (a), wherein Rk (k:1-8) represents hydrogen, halogeno, optionally substituted lower alkyl, etc., and either R7 or R8 represents a group represented by formula (b), wherein rings A and B represent each independently an optionally substituted aromatic hydrocarbon or unsaturated heterocyclic ring; and D represents an optionally protected carboxyl group.

  通式(A)代表的融合环羧酸衍生物及其药理学上可接受的盐，可提供维甲酸受体激动剂活性极佳的药物，其中符号代表单键或双键；X、Y、Z、P、Q、U、V 和 W 各自代表-O-、-S- 或式(a)代表的基团，其中 Rk (k:1-8) 代表氢、卤素、任选取代的低级烷基等、以及 R7 或 R8 代表由式（b）表示的基团，其中环 A 和 B 各自独立地代表任选取代的芳香烃或不饱和杂环；以及 D 代表任选保护的羧基。
• METHODS FOR PREVENTING, INHIBITING OR TREATING GRAFT REJECTION REACTIONS IN GRAFT-VERSUS-HOST DISEASE (GVHD) AND ORGAN TRANSPLANTATION
  申请人：Eisai Co., Ltd.

  公开号：EP0930075A1

  公开（公告）日：1999-07-21

  The present invention provides remedies for graft-versus-host disease (GVHD) and graft rejection reactions in organ transplantation which comprise retinoic acid receptor (RAR) agonists as an active ingredient. Main examples thereof include 9-(4-methoxy-2,3,6-trimethylphenyl)-7,8-dimethylnona-2,4,6,8-tetraen-1-oic acid, 4-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalen-2-yl)propenyl]benzoic acid, 4-2-[5-(4,7-dimethylbenzofuran-2-yl)pyrroyl]}benzoic acid, 4-2-[5-(5-chloro-7-ethylbenzofuran-2-yl)pyrrolyl]}benzoic acid and 4-2-[5-(4,7-dimethylbenzothiophen-2-yl)pyrrolyl]}benzoic acid.

  本发明提供了治疗器官移植中移植物抗宿主病（GVHD）和移植物排斥反应的药物，其活性成分包括视黄酸受体（RAR）激动剂。其主要例子包括 9-(4-甲氧基-2,3,6-三甲基苯基)-7,8-二甲基萘-2,4,6,8-四烯-1-酸、4-[(E)-2-(5,6,7,8-四氢-5,5,8,8-四甲基萘-2-基)丙烯基]苯甲酸、4-2-[5-(4,7-二甲基苯并呋喃-2-基)吡咯基]}苯甲酸、4-2-[5-(5-氯-7-乙基苯并呋喃-2-基)吡咯基]}苯甲酸和 4-2-[5-(4,7-二甲基苯并噻吩-2-基)吡咯基]}苯甲酸。
• RETINOIC ACID AGONISTS AS PREVENTIVE AND THERAPEUTIC AGENTS FOR NEPHRITIS
  申请人：Eisai Co., Ltd.

  公开号：EP1025857A1

  公开（公告）日：2000-08-09

  Therapeutic or preventive agents for system lupus erythematosus, glomerulonephritis, lupus nephritis, idiopathic thrombocytopenic purpura or autoimmune anemia, which can be substituted for conventional steroid preparations or immunosuppressive agents. The active ingredients of the therapeutic or preventive agents are agonists for retinoic acid receptors, particularly retinoic receptor, subtype α (i.e., RAR α), and examples of the agonists include (1) carboxylic acid derivatives bearing fused rings as represented by general formula (I) wherein rings L and M are fused with each other, and are each independently an optionally substituted aromatic hydrocarbon ring or an optimally substituted heterocycle; rings A and B are each independently an optionally substituted aromatic hydrocarbon ring or a heterocycle; and D is optionally protected carboxyl, and (2) 4-[(3,5-bistrimethylsilylphenyl)carbonyl]amino}benzoic acid and 42-[5-(3-methoxymethyl-5,6,7,8-tetrahydro-5,5,8,8,-tetramethylnaphthalen-2-yl)-pyrrolyl]}benzoic acid.

  治疗或预防系统性红斑狼疮、肾小球肾炎、狼疮性肾炎、特发性血小板减少性紫癜或自身免疫性贫血的药物，可替代传统的类固醇制剂或免疫抑制剂。治疗剂或预防剂的有效成分是视黄酸受体激动剂，特别是视黄酸受体α亚型（即 RAR α、RAR β 和 RAR β 例子）、RAR α）的激动剂，激动剂的例子包括 (1) 如通式（I）所示的带有融合环的羧酸衍生物，其中环 L 和 M 相互融合，且各自独立地为任选取代的芳香烃环或最佳取代的杂环；(2) 4-[(3,5-二甲基硅基苯基)羰基]氨基}苯甲酸和 42-[5-(3-甲氧基甲基-5,6,7,8-四氢-5,5,8,8,-四甲基萘-2-基)-吡咯基]}苯甲酸。
• 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。
• Bicycloheteroaryl-Heteroaryl-Benzoic Acid Compounds as Retinoic Acid Receptor Beta (RARBeta) Agonists
  申请人：King's College London

  公开号：US20170327489A1

  公开（公告）日：2017-11-16

  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.