4-amino-5-chloro-2,2-dimethyl-2,3-dihydrobenzo[b]furan-7-carboxylic acid | 132976-67-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-amino-5-chloro-2,2-dimethyl-2,3-dihydrobenzo[b]furan-7-carboxylic acid
• 英文别名: 4-amino-5-chloro-2,2-dimethyl-2,3-dihydro-7-benzofurancarboxylic acid；4-amino-5-chloro-2,3-dihydro-2,2-dimethyl-7-benzofurancarboxylic acid；4-amino-5-chloro-2,2-dimethyl-3H-1-benzofuran-7-carboxylic acid
• CAS: 132976-67-1
• 化学式: C₁₁H₁₂ClNO₃
• 分子量: 241.674
• InChiKey: ALEHRPIPWUVBHE-UHFFFAOYSA-N

物化性质

• 沸点：
  393.1±42.0 °C(Predicted)
• 密度：
  1.383±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  72.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-5-chloro-2,2-dimethyl-2,3-dihydrobenzo[b]furan-7-carboxylic acid 生成 4-Amino-N-[2-(1-azabicyclo[3.3.0]octan-5-yl)ethyl]-5-chloro-2,2-dimethyl-2,3-dihydrobenzo[b]furan-7-carboxamide
  参考文献：
  名称：

  Benzo[B]Furancarboxamide derivatives, process for the preparation of

  摘要：

  公开了一种苯并[b]呋喃羧酰胺衍生物，其化学式为##STR1##其中R.sup.a，R.sup.b，R.sup.c和R.sup.d分别是氢原子或较低的烷基基团；R.sup.e是氢原子，氨基基团，较低的烷基氨基基团或酰胺基团；X是氢原子或卤原子；n是1-5的整数，包括外消旋化合物和立体异构体，化合物和盐的制备过程以及用于改善过度活动症的用途。

  公开号：

  US05442077A1
• 作为产物：
  描述：

  methyl 4-(acetylamino)-2-[(2-methyl-2-propenyl)oxy]benzoate 在 N-甲基吡咯烷酮 、 sodium hydroxide 、 N-氯代丁二酰亚胺 、 硫酸 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 4-amino-5-chloro-2,2-dimethyl-2,3-dihydrobenzo[b]furan-7-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationship of 3-Substituted Benzamide, Benzo(b)furan-7-carboxamide, 2,3-Dihydrobenzo(b)furan-7-carboxamide, and Indole-5-carboxamide Derivatives as Selective Serotonin 5-HT4 Receptor Agonits.

  摘要：

  标题化合物（6-9）已被合成并在体外测试中评估其对血清素5-HT4的激动活性。在苯酰胺的3位引入丙基或烯丙基仅导致激动活性的轻微增强。而构建苯并[b]呱骨架和2,3-二氢苯并[b]呱骨架则显著增强了活性。4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2-甲基苯并[b]呱-7-羧酰胺（7b）半富马酸盐的效力与西沙必利相当。4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2,3-二氢-2-甲基苯并[b]呱-7-羧酰胺（8a）半富马酸盐，4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2,3-二氢-2-乙基苯并[b]呱-7-羧酰胺（8c）半富马酸盐，以及4-氨基-N-[2-(1-叠氮环[3.3.0]八烷-5-基)乙基]-5-氯-2,3-二氢-2,3-二甲基苯并[b]呱-7-羧酰胺（8d）半富马酸盐的效力均优于西沙必利。此外，8a半富马酸盐在体外测试中未表现出对多巴胺D1、D2、血清素5-HT1、5-HT2及毒蕈碱M1、M2受体的结合活性。另一方面，构建吲哚骨架则导致活性显著降低。

  DOI：

  10.1248/cpb.46.42

文献信息

• Esters of 3-hydroxy-piperidinemethanol derivatives
  申请人：Janssen Pharmaceutica N.V.

  公开号：US06096761A1

  公开（公告）日：2000-08-01

  The present invention of compounds of formula (I), ##STR1## a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, R.sup.1 is C.sub.1-6 alkyloxy, C.sub.2-6 alkenyloxy or C.sub.2-6 alkynyloxy; R.sup.2 is hydrogen or C.sub.1-6 alkyloxy, or when taken together R.sup.1 and R.sup.2 may form a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C.sub.1-6 alkyl; R.sup.3 is hydrogen or halo; R.sup.4 is hydrogen or C.sub.1-6 alkyl; L is C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, C.sub.2-6 alkenyl optionally substituted with aryl, or L is a radical of formula -Alk-R.sup.5 -, Alk-X--R.sup.6, -Alk-Y--C(.dbd.O)--R.sup.8, or -Alk-Y--C(.dbd.O)--NR.sup.10 R.sup.11 wherein each Alk is C.sub.1-12 alkanediyl; and R.sup.5 is hydrogen, cyano, C.sub.1-6 alkylsulfonylamino, C.sub.3-6 cycloalkyl, C.sub.5-6 cycloalkanone, aryl, di(aryl)methyl or a heterocyclic ringsystem; R.sup.6 is hydrogen, C.sub.1-6 alkyl, hydroxyC.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl or heterocyclic ringsystem; X is O, S, SO.sub.2 or NR.sup.7 ; said R.sub.7 being hydrogen, C.sub.1-6 alkyl or aryl; R.sup.8 is hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl, arylC.sub.1-6 alkyl, di(aryl)methyl, C.sub.1-6 alkyloxy or hydroxy; Y is NR.sup.9 or a direct bond; said R.sup.9 being hydrogen, C.sub.1-6 alkyl or aryl R.sup.10 and R.sup.11 each independently are hydrogen, C.sub.1-6 alkyl, C.sub.3-6 cycloalkyl, aryl or arylC.sub.1-6 alkyl, or R.sup.10 and R.sup.11 combined with the nitrogen atom bearing R.sup.10 and R.sup.11 may form a pyrrolidinyl or piperidinyl ring both being optionally substituted with C.sub.1-6 alkyl, amino or mono or di(C.sub.1-6 alkyl)amino, or said R.sup.10 and R.sup.11 combined with the nitrogen bearing R.sup.10 and R.sup.11 may form a piperazinyl or 4-morpholinyl radical both being optionally substituted with C.sub.1-6 alkyl. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating conditions which are related to impairment of gastric emptying.

  本发明涉及化合物的公式（I），其立体化学异构体，N-氧化物形式或其药学上可接受的酸盐，其中R.sup.1为C.sub.1-6烷氧基，C.sub.2-6烯氧基或C.sub.2-6炔基氧基；R.sup.2为氢或C.sub.1-6烷氧基，或当R.sup.1和R.sup.2结合在一起时，可以形成一个具有以下结构的二价基团，其中在所述的二价基团中，一个或两个氢原子可以被C.sub.1-6烷基取代；R.sup.3为氢或卤素；R.sup.4为氢或C.sub.1-6烷基；L为C.sub.3-6环烷基，C.sub.5-6环戊酮，C.sub.2-6烯基，可选地取代芳基，或L为以下结构的基团-Alk-R.sup.5-，Alk-X--R.sup.6，-Alk-Y--C(.dbd.O)--R.sup.8或-Alk-Y--C(.dbd.O)--NR.sup.10R.sup.11，其中每个Alk为C.sub.1-12烷二基；R.sup.5为氢，氰基，C.sub.1-6烷基磺酰氨基，C.sub.3-6环烷基，C.sub.5-6环戊酮，芳基，二(芳基)甲基或杂环戒系统；R.sup.6为氢，C.sub.1-6烷基，羟基C.sub.1-6烷基，C.sub.3-6环烷基，芳基或杂环戒系统；X为O，S，SO.sub.2或NR.sup.7；其中R.sub.7为氢，C.sub.1-6烷基或芳基；R.sup.8为氢，C.sub.1-6烷基，C.sub.3-6环烷基，芳基，芳基C.sub.1-6烷基，二(芳基)甲基，C.sub.1-6烷氧基或羟基；Y为NR.sup.9或直接键；其中R.sup.9为氢，C.sub.1-6烷基或芳基，R.sup.10和R.sup.11各自独立地为氢，C.sub.1-6烷基，C.sub.3-6环烷基，芳基或芳基C.sub.1-6烷基，或R.sup.10和R.sup.11与携带R.sup.10和R.sup.11的氮原子结合，可以形成一个取代有C.sub.1-6烷基，氨基或单或二(C.sub.1-6烷基)氨基的吡咯烷基或哌啶烷基环，或R.sup.10和R.sup.11与携带R.sup.10和R.sup.11的氮原子结合，可以形成一个取代有C.sub.1-6烷基的哌嗪基或4-吗啉基基团。公开了制备所述产品的方法，包括所述产品的配方以及它们作为药物的用途，特别是用于治疗与胃排空障碍相关的疾病。
• Dimethylbenzofuran and dimethylbenzopyran derivatives and their use as
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05674868A1

  公开（公告）日：1997-10-07

  Method of treating 5-HT.sub.3 -mediated disorders, which comprises systemic administration of an effective amount of a compound of formula (I) ##STR1## the pharmaceutically acceptable acid addition salt forms and the stereochemically isomeric forms thereof, wherein R.sup.1 and R.sup.2 represent hydrogen, or R.sup.1 and R.sup.2 taken together form a bivalent radical of formula --CH.dbd.CH--CH.dbd.CH-- (a), --CH.dbd.C(Cl)--CH.dbd.CH-- (b) or --CH.dbd.CH--C(Cl).dbd.CH-- (c); n represents 2, 3 or 4; R.sup.3 represents hydrogen or methoxy; m represents 1 or 2; R.sup.4 represents hydrogen, amino or C.sub.1-3 -alkylcarbonylamino; and R.sup.5 represents hydrogen or halo; novel compounds; compositions; processes for preparing novel compounds and intermediates.

  治疗5-HT.sub.3介导的疾病的方法，包括系统给药有效量的式(I)化合物 ##STR1## 其药学上可接受的酸加成盐形式及其立体化学异构体形式，其中R.sup.1和R.sup.2代表氢，或者R.sup.1和R.sup.2一起形成式--CH.dbd.CH--CH.dbd.CH-- (a)、--CH.dbd.C(Cl)--CH.dbd.CH-- (b)或--CH.dbd.CH--C(Cl).dbd.CH-- (c)的二价基团；n代表2、3或4；R.sup.3代表氢或甲氧基；m代表1或2；R.sup.4代表氢、氨基或C.sub.1-3 -烷基羰基氨基；R.sup.5代表氢或卤素；新化合物；组合物；制备新化合物及其中间体的方法。
• N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05374637A1

  公开（公告）日：1994-12-20

  N-(3-hydroxy-4-piperidinyl)(dihydrobenzofuran, dihydro-2H-benzopyran or dihydrobenzodioxin)carboxamide derivatives, their N-oxide forms and pharmaceutically acceptable salts having gastrointestinal motility stimulating properties, compositions containing these compounds as active ingredient and methods of treating warm-blooded animals suffering from the decreased peristalsis of the gastrointestinal system.

  N-(3-羟基-4-哌啶基)(二氢苯并呋喃、二氢-2H-苯并吡喃或二氢苯并二氧杂环)羧酰胺衍生物，其N-氧化物形式和具有促进胃肠道蠕动性能的药用可接受盐，包含这些化合物作为活性成分的组合物以及治疗患有胃肠系统蠕动减弱的温血动物的方法。
• Benzo[b]furancarboxamide derivatives, process for their preparation and their use as gastrointestinal mobility-enhancing agents
  申请人：SANWA KAGAKU KENKYUSHO CO., LTD.

  公开号：EP0640602A1

  公开（公告）日：1995-03-01

  There are disclosed a benzo[b]furancarboxamide derivative of the formula    wherein Ra, Rb, Rc and Rd are a hydrogen atom or lower alkyl group, respectively; Re is a hydrogen atom, amino radical, lower alkylamino group or acylamino group; X is a hydrogen atom or halogen atom; and n is an integer of 1 - 5, and including racemic compounds and stereo-isomers thereof, a salt of the compounds, a process for the preparation of the compounds and salts as well as their use as gastrointestinal motility-enhancing agents.

  本发明涉及一种苯并[b]呋喃羧酰胺衍生物，其化学式为   其中，Ra、Rb、Rc和Rd分别为氢原子或较低的烷基基团；Re为氢原子、氨基基团、较低的烷基氨基基团或酰基氨基基团；X为氢原子或卤原子；n为1-5的整数，并包括其外消旋化合物和立体异构体、化合物的盐、制备化合物和盐的方法以及它们作为胃肠动力增强剂的用途。
• 5-halo-2,3-dihydro-2,2-dimethylbenzofuran-7-carboxylic acids useful as
  申请人：Eli Lilly and Company

  公开号：US04921982A1

  公开（公告）日：1990-05-01

  This invention provides bicyclic carboxylic esters and amides, their pharmaceutical formulations, and a method for their use in treating migraine, emesis, gastrointestinal disorders, schizophrenia, or anxiety in mammals.

  本发明提供了双环羧酸酯和酰胺、它们的药物配方以及一种用于治疗哺乳动物偏头痛、呕吐、胃肠道疾病、精神分裂症或焦虑症的方法。