4-[5-(4,7-dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid | 196517-43-8

• 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-dimethylbenzofuran-2-yl)pyrrol-2-yl]benzoic acid
• 英文别名: Benzoic acid, 4-(5-(4,7-dimethyl-2-benzofuranyl)-1H-pyrrol-2-yl)-；4-[5-(4,7-dimethyl-1-benzofuran-2-yl)-1H-pyrrol-2-yl]benzoic acid
• CAS: 196517-43-8
• 化学式: C₂₁H₁₇NO₃
• 分子量: 331.371
• InChiKey: LSZNZLWBRQAWNH-UHFFFAOYSA-N

物化性质

• 熔点：
  177-178 °C
• 沸点：
  586.9±50.0 °C(Predicted)
• 密度：
  1.272±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 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：

  4,7-二甲基苯并呋喃 在 乙酸铵 、 sodium hydroxide 、 正丁基锂 、 3-苄基羟乙基甲基噻唑氯化锂 、 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 为溶剂， 反应 3.75h， 生成 4-[5-(4,7-dimethylbenzofuran-2-yl)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。
• MEMORY FIXATION ACCELERATOR
  申请人：Research Foundation Itsuu Laboratory

  公开号：EP1733722A1

  公开（公告）日：2006-12-20

  A medicament for promoting memory consolidation, which comprises, as an active ingredient, a non-natural retinoid, preferably a retinoid having a basic skeleton comprising an aromatic ring bound with an aromatic carboxylic acid or tropolone by means of a bridging group, more preferably 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid or 4-[(3,5-bis-trimethylsilylphenyl)-carboxamido]benzoic acid.

  一种促进记忆巩固的药物，其活性成分包括一种非天然维甲酸，最好是一种具有基本骨架的维甲酸，基本骨架包括一个芳香环，芳香环通过桥基与芳香族羧酸或四氢萘酮结合、更优选 4-[(5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基)氨基甲酰基]苯甲酸或 4-[(3,5-二三甲硅基苯基)-甲酰氨基]苯甲酸。
• PHARMACEUTICAL FOR USE IN PREVENTION AND/OR TREATMENT OF BOWEL DISEASE
  申请人：R & R Inc.

  公开号：EP1930001A1

  公开（公告）日：2008-06-11

  A medicament for preventive and/or therapeutic treatment of a bowel diseases such as inflammatory bowel diseases including Crohn's disease, which comprises as an active ingredient a retinoid such as, for example, 4-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]benzoic acid.

  一种用于预防和/或治疗肠道疾病（如炎症性肠病，包括克罗恩病）的药物，其活性成分包括维甲酸，例如 4-[(5,6,7,8-四氢-5,5,8,8-四甲基-2-萘基)氨基甲酰基]苯甲酸。