2-acetoxymethyl-4,7-difluoro-2,3-dihydrobenzofuran | 196519-73-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 香豆素
• 英文名称: 2-acetoxymethyl-4,7-difluoro-2,3-dihydrobenzofuran
• 英文别名: (4,7-difluoro-2,3-dihydro-1-benzofuran-2-yl)methyl acetate
• CAS: 196519-73-0
• 化学式: C₁₁H₁₀F₂O₃
• 分子量: 228.195
• InChiKey: JTRJGPMAXXXWNC-UHFFFAOYSA-N

物化性质

• 沸点：
  276.9±40.0 °C(Predicted)
• 密度：
  1.299±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-acetoxymethyl-4,7-difluoro-2,3-dihydrobenzofuran 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 potassium tert-butylate 作用下， 以 四氯化碳 、 叔丁醇 为溶剂， 反应 3.25h， 生成 (E) 2-Acetoxymethyl-4,7-difluorobenzofuran
  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
• 作为产物：
  描述：

  2,5-二氟苯酚 在 吡啶 、 氢氧化钾 、 potassium carbonate 、 N,N-二甲基苯胺 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 2-acetoxymethyl-4,7-difluoro-2,3-dihydrobenzofuran
  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

• Carboxylic acid derivatives having fused rings
  申请人：Eisai Co., Ltd.

  公开号：US06110959A1

  公开（公告）日：2000-08-29

  The present invention provides a medicament exhibiting excellent retinoic acid receptor agonism. A Carboxylic acid derivative having a fused ring which is represented by the following formula or a pharmacologically acceptable salt thereof: ##STR1## wherein the symbol ##STR2## represents a single bond or a double bond; X, Y, Z, P, Q, U, V and W are each a group represented by the formula: --O-- or --S--, or a group represented by the formula: ##STR3## [wherein R.sup.k (k: 1 to 8) is hydrogen, halogeno, optionally substituted lower alkyl or the like, with either of R.sup.7 and R.sup.8 being a group represented by the formula: ##STR4## (wherein A and B are each independently an optionally substituted aromatic hydrocarbon ring or an optionally substituted unsaturated heterocycle; and D is optionally protected carboxyl)]}.

  本发明提供了一种表现出优异的视黄酸受体激动作用的药物。具有以下式子所代表的融合环的羧酸衍生物或其药理学上可接受的盐：##STR1## 其中符号##STR2##代表单键或双键；X、Y、Z、P、Q、U、V和W分别是由式子表示的基团：--O--或--S--，或由式子表示的基团：##STR3## [其中R.sup.k（k：1至8）是氢、卤代、可选择取代的较低烷基或类似物，R.sup.7和R.sup.8中的任一者是由式子表示的基团：##STR4##（其中A和B各自独立地是可选择取代的芳香烃环或可选择取代的不饱和杂环；D是可选择保护的羧基）}。
• 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：US06258811B1

  公开（公告）日：2001-07-10

  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.

  该发明提供了用作移植物抗宿主病（GVHD）和器官移植中移植排斥反应的药物，其包括视黄酸受体（RAR）激动剂作为活性成分。其主要示例包括9-（4-甲氧基-2,3,6-三甲基苯基）-7,8-二甲基壬-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：US06355669B1

  公开（公告）日：2002-03-12

  The present invention provides a therapeutic or prophylactic agent as a substitute for conventional steroids or immunosuppressive agents to treat or prevent systemic erythematosus, glomerulonephritis, lupus nephritis, idiopathic thrombocytopenic purpura or autoimmune anemia. The agent comprises a retinoic acid receptor agonist, specifically a retinoic acid receptor subtype &agr; (RAR&agr;) agonist, including for example: (1) carboxylic acid compounds having condensed rings represented by the following formula:  (wherein the rings L and M are condensed, are the same as or different from each other, and represent an aromatic hydrocarbon which may have a substituent group or a heterocycle which may have a substituent group; the rings A and B are independent of each other and represent an aromatic hydrocarbon ring or heterocycle which may have a substituent group; and D represents a carboxyl group which may have a protective group), (2) 4-{[(3,5-bistrimethylsilylphenyl)carbonyl]amino}benzoic acid, 4-{2-[5-(3-methoxymethyl-5,6,7,8-tetrahydro-5,5,8,8-tetramethylnaphthalene-2-yl)pyrrolyl]}benzoic acid, etc.

  本发明提供了一种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替代传统类固醇或免疫抑制剂的治疗或预防剂。该剂包括一种视黄酸受体激动剂，特别是视黄酸受体亚型α（RARα）激动剂，例如：（1）具有以下结构的环状羧酸化合物：（其中环L和M为缩合环，与彼此相同或不同，并表示可能具有取代基的芳香族碳氢化合物或可能具有取代基的杂环；环A和B彼此独立，表示可能具有取代基的芳香族碳氢环或杂环；D表示可能具有保护基的羧基），（2）4-【（3,5-双三甲基硅基苯基）甲酰基】氨基苯甲酸、4-【2-（5-（3-甲氧甲基-5,6,7,8-四氢-5,5,8,8-四甲基萘-2-基）吡咯基）】苯甲酸等。
• 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。