5-氯-2,3-二氢苯并[b]呋喃-7-羧酸 | 108551-58-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 5-氯-2,3-二氢苯并[b]呋喃-7-羧酸
• 英文名称: 5-chloro-2,3-dihydrobenzo[b]furan-7-carboxylic acid
• 英文别名: 5-chloro-2,3-dihydro-benzo[b]furan-7-carboxylic acid；2,3-dihydro-5-chlorobenzofuran-7-carboxylic acid；2,3-diydro-5-chlorobenzofuran-7-carboxylic acid；5-chloro-2,3-dihydro-7-benzofurancarboxylic acid；5-chloro-2,3-dihydrobenzofuran-7-carboxylic acid；7-carboxy-5-chlorodihydrobenzofuran；5-Chloro-2,3-dihydro-1-benzofuran-7-carboxylic acid
• CAS: 108551-58-2
• 化学式: C₉H₇ClO₃
• mdl: MFCD20482622
• 分子量: 198.606
• InChiKey: SGPAPRPKRANLEF-UHFFFAOYSA-N

物化性质

• 熔点：
  226 °C
• 沸点：
  363.3±42.0 °C(Predicted)
• 密度：
  1.481±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.222
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-氯-2,3-二氢苯并[b]呋喃-7-羧酸 生成 N-(1-Cyclohexenylmethyl-2-pyrrolidinylmethyl)-5-chloro-2,3-dihydrobenzofuran-7-carboxamide
  参考文献：
  名称：

  FRANCESCHINI, J.;MARGARIT, JOSETTE

  摘要：

  DOI：

文献信息

• 4-(aminomethyl)-piperidine benzamides for treating gastrointestinal disorders
  申请人：Janssen Pharmaceutica, N.V.

  公开号：US06544997B1

  公开（公告）日：2003-04-08

  The present invention of compounds of formula (I) a stereochemically isomeric form thereof, an N-oxide form thereof or a pharmaceutically acceptable acid addition salt thereof, —R1—R2— is a bivalent radical of formula wherein in said bivalent radicals one or two hydrogen atoms may be substituted with C1-6alkyl or hydroxy; R3 is hydrogen or halo; R4 is hydrogen or C1-6alkyl; R5 is hydrogen or C1-6alkyl; L is C3-6cycloalkyl, oxoC5-6cycloalkyl, C2-6alkenyl, or L is a radical of formula —Alk—R6—, Alk—X—R7, —Alk—Y—C(═O)—R9, or —Alk—Y—C(═O)—NR11R12 wherein each Alk is C1-12alkanediyl; and R6 is hydrogen, amino, cyano, C1-6alkylsulfonylamino, C3-6cycloalkyl, oxoC5-6cycloalkyl, aryl or a heterocyclic ringsystem; R7 is hydrogen, C1-6alkyl, hydroxyC1-6alkyl, C3-6cycloalkyl, aryl or a heterocyclic ringsystem; X is O, S, SO2 or NR8; said R8 being hydrogen or C1-6alkyl; R9 is hydrogen, C1-6alkyl, C3-6cycloalkyl, C1-6alkyloxy, hydroxy or aryl; Y is a direct bond or NR10; said R10 being hydrogen, or C1-6alkyl; R11 and R12 each independently are hydrogen, C1-6alkyl, C3-6cycloalkyl, or R11 and R12 combined with the nitrogen atom may form an optionally substituted pyrrolidinyl, piperidinyl, piperazinyl or 4-morpholinyl ring. Processes for preparing said products, formulations comprising said products and their use as a medicine are disclosed, in particular for treating or preventing gastrointestinal disorders.

  本发明涉及化合物的公式(I)，其立体化学异构体形式，N-氧化物形式或药用可接受的酸加成盐形式，其中—R1—R2—是一个公式的双价基团，在所述双价基团中，一个或两个氢原子可以被C1-6烷基或羟基取代；R3为氢或卤素；R4为氢或C1-6烷基；R5为氢或C1-6烷基；L为C3-6环烷基，氧代C5-6环烷基，C2-6烯基，或L为公式—Alk—R6—、Alk—X—R7、—Alk—Y—C(═O)—R9或—Alk—Y—C(═O)—NR11R12的基团，其中每个Alk为C1-12烷二基；R6为氢、氨基、氰基、C1-6烷基磺酰氨基、C3-6环烷基、氧代C5-6环烷基、芳基或杂环体；R7为氢、C1-6烷基、羟基C1-6烷基、C3-6环烷基、芳基或杂环体；X为O、S、SO2或NR8；其中R8为氢或C1-6烷基；R9为氢、C1-6烷基、C3-6环烷基、C1-6烷氧基、羟基或芳基；Y为直接键或NR10；其中R10为氢或C1-6烷基；R11和R12各自独立地为氢、C1-6烷基、C3-6环烷基，或R11和R12与氮原子结合可形成选择性取代的吡咯烷基、哌啶基、哌嗪基或4-吗啉基环。公开了制备所述产品的方法、包含所述产品的配方以及它们作为药物的用途，特别用于治疗或预防胃肠道疾病。
• Substituted heteroaryl pyridopyrimidone derivatives
  申请人：Sanofi-Aventis

  公开号：EP1939187A1

  公开（公告）日：2008-07-02

  A pyrimidone derivative represented by formula (I) or a salt thereof, or a solvate thereof or a hydrate thereof : wherein: Y represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom; Z represents a bond, an oxygen atom, a nitrogen atom, a sulphur atom, a methylene group optionally substituted by one or two groups chosen from a C1-6 alkyl group, a hydroxyl group, a C1-6 alkoxy group, a C1-2 perhalogenated alkyl group or an amino group; R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring; R2 represents a 4-15 membered heterocyclic group , R3 represents a hydrogen atom, a C1-6 alkyl group or a halogen atom; R4 and R5 represent, each independently, a hydrogen atom, a C1-6 alkyl group, optionally substituted by 1 to 4 substituents selected from a halogen atom, a phenyl group, a hydroxyl group or a C1-6 alkoxy group; R6 represents a hydrogen atom, a C1-6 alkyl group ; a cycloalkyl group, or a halogen atom; R7 represents a hydrogen atom or a C1-6 alkyl group; n represents 0 to 3; m represents 0 to 1; o represents 0 to 2; in the form of a free base or of an addition salt with an acid. The invention relates also to a medicament comprising the said derivative or a salt thereof as an active ingredient which is used for preventive and/or therapeutic treatment of a neurodegenerative disease caused by abnormal activity of GSK3β, such as Alzheimer disease.

  公式（I）表示的嘧啶酮衍生物或其盐，溶剂化合物或水合物：其中：Y代表两个氢原子、硫原子、氧原子或C1-2烷基基团和一个氢原子；Z代表键、氧原子、氮原子、硫原子、一个亚甲基基团，可选地由C1-6烷基基团、羟基、C1-6烷氧基、C1-2全卤代烷基或氨基中选择的一种或两种基团取代的亚甲基基团；R1代表2、3或4-吡啶环或2、4或5-嘧啶环；R2代表4-15成员的杂环基团，R3代表氢原子、C1-6烷基基团或卤原子；R4和R5分别代表氢原子、C1-6烷基基团，可选地取代1至4个取代基，所选取代基来自卤原子、苯基、羟基或C1-6烷氧基；R6代表氢原子、C1-6烷基基团；环烷基基团或卤原子；R7代表氢原子或C1-6烷基基团；n表示0到3；m表示0到1；o表示0到2；以自由碱或与酸的加成盐的形式存在。该发明还涉及一种药物，包括所述衍生物或其盐作为活性成分，用于预防和/或治疗由GSK3β异常活性引起的神经退行性疾病，如阿尔茨海默病。
• Synthesis and Structure−Affinity Relationships of Novel <i>N</i>-(1-Ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides with Potent Serotonin 5-HT₃ and Dopamine D₂ Receptor Antagonistic Activity
  作者：Yoshimi Hirokawa、Iwao Fujiwara、Kenji Suzuki、Hiroshi Harada、Takashi Yoshikawa、Naoyuki Yoshida、Shiro Kato

  DOI：10.1021/jm020270n

  日期：2003.2.1

  dopamine D(2) receptor while keeping a potent serotonin 5-HT(3) receptor binding affinity. As a result of structure-affinity relationships, the 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxamide 53 was selected as the most promising product showing a high binding affinity for both receptors. Compound 53 affinity for the dopamine D(2) and serotonin 5-HT(3) receptors was much more potent than that of

  制备了由相应的苯甲酰胺5衍生的N-（1-乙基-4-甲基六氢-1,4-二氮杂-6-6-基）吡啶-3-甲酰胺的结构原始系列，并评估了其对多巴胺D（ 2）和分别使用大鼠纹状体和大鼠皮质膜的血清素5-HT（3）受体。许多合成的吡啶-3-羧酰胺对5-羟色胺5-HT（3）受体具有纳摩尔结合亲和力，对多巴胺D（2）受体具有中等至高结合亲和力。在吡啶环的5-位和6-位上分别引入更具亲脂性的溴原子和甲基氨基，增强了对多巴胺D（2）受体的亲和力，同时保持了强大的5-羟色胺5-HT（3）受体结合亲和力。由于结构相似性关系，选择5-溴-2-甲氧基-6-甲基氨基吡啶-3-羧酰胺53作为最有前途的产品，该产品对两种受体都具有高结合亲和力。化合物53对多巴胺D（2）和5-羟色胺5-HT（3）受体的亲和力比甲氧氯普胺（多巴胺D（2）受体； 23.3 nM对444 nM，5-羟色胺5-HT（3）受体的亲和力强得多。 0.97
• Dihydrobenzofuran- and chroman-carboxamide derivatives, processes for
  申请人：Laboratoires Delagrange

  公开号：US05006570A1

  公开（公告）日：1991-04-09

  The invention relates to new dihydrobenzofuran- and chroman-carboxamide derivatives of the general formula: ##STR1## in which R and R' are each hydrogen or methyl; n is 1 or 2; m is 1 or 2; Z is either ##STR2## wherein R.sub.1 and R.sub.2 are lower alkyl, or ##STR3## wherein R.sub.3 is alkyl, alkenyl, cycloalkyl-alkyl, cycloalkenyl-alkyl, X is H, NH.sub.2, methoxy, or methyl and Y is H, Cl, cycloalkylmethylsulfonyl, alkylsulfamoyl or alkylsulfonyl and to their pharmacologically acceptable acid addition salts and their optical isomers, to the processes for the preparation thereof and to the use thereof as medicaments, especially as neuroleptics.

  该发明涉及一般式的新二氢苯并呋喃和色苷-羧酰胺衍生物：其中R和R'分别为氢或甲基；n为1或2；m为1或2；Z为或其中R1和R2为较低烷基，或其中R3为烷基、烯基、环烷烷基、环烯烷基，X为H、NH2、甲氧基或甲基，Y为H、Cl、环烷基甲磺酰基、烷基磺酰胺基或烷基磺酰基，以及它们的药理学可接受的酸加盐和光学异构体，以及其制备方法和作为药物的用途，特别是作为神经阻滞药。
• Synthesis and Structure-Activity Relationships of 2,3-Dihydrobenzofuran-7-carboxamide Derivatives as Potent Serotonin-3 (5-HT3) Receptor Antagonists.
  作者：Takanobu KUROITA、Mitsuyoshi YASUMOTO、Kenichi INABA、Masamitsu SAKAMORI、Shuzo TAKEHARA、Takeshi KAWAKITA

  DOI：10.1248/cpb.42.95

  日期：——

  mide derivatives were synthesized and evaluated for serotonin-3 (5-HT3) receptor antagonistic activities assessed by 5-HT3 receptor binding (in vitro) and by the ability to antagonize the von Bezold-Jarisch reflex in rats (in vivo). In these compounds, 1-azabicyclo[2.2.2]oct-3-yl derivatives were more potent than 8-methyl-8-azabicyclo[3.2.1]oct-3-yl derivatives for 5-HT3 receptor antagonistic activities

  合成了一系列N-（氮杂双环-3-基）-2,3-二氢苯并呋喃-7-羧酰胺衍生物，并通过5-HT3受体结合评估了5-羟色胺3（5-HT3）受体拮抗活性（体外）。并具有拮抗大鼠体内von Bezold-Jarisch反射的能力（体内）。在这些化合物中，1-氮杂双环[2.2.2]辛-3-基衍生物对5-HT3受体的拮抗作用比8-甲基-8氮杂双环[3.2.1]辛-3-基衍生物更有效。在二氢苯并呋喃环的2位上引入甲基可提高药理活性（二甲基>单甲基>二氢）。此外，制备了二甲基，单甲基和二氢苯并呋喃衍生物的立体异构体，以评估其5-HT 3受体结合亲和力的立体选择性。关于基本部分，具有（S）-1-氮杂双环[2.2.2] octan-3-基部分的化合物比其对应物更有效。关于二氢苯并呋喃环的2位上的甲基取代基，效力的等级顺序为二甲基＞或＝（2S）-甲基＞（2R）-甲基＞二氢。这些结果表明，二氢苯并呋喃部分的（2S