7-(3-chloropropoxy)-3-methyl-chromen-4-one | 172739-43-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 7-(3-chloropropoxy)-3-methyl-chromen-4-one
• 英文别名: 7-(3-Chloropropoxy)-3-methylchromen-4-one
• CAS: 172739-43-4
• 化学式: C₁₃H₁₃ClO₃
• 分子量: 252.697
• InChiKey: JXCPTXQVLPJEPM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-氟-3-(哌啶-4-基)苯并[D]异恶唑 、 7-(3-chloropropoxy)-3-methyl-chromen-4-one 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以43%的产率得到7-(3-(4-(6-fluoro-1,2-benzisoxazole-3-yl)piperidin-1-yl)propoxy)-3-methyl-chromen-4-one
  参考文献：
  名称：

  7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics. 2. Pharmacological Profile of 7-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (Abaperidone, FI-8602)

  摘要：

  A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for Dp receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypical antipsychotics. Several agents also displayed a high potency in the climbing mice assay on oral administration, suggesting a potent antipsychotic effect as compared to reference standards. Compound 23 was selected for fur ther pharmacological evaluation. induction of catalepsy and inhibition of stereotypies weaker than standards, along with a lower increase in serum prolactin levels, were indicative of a potential atypical profile for this compound. From these results, 7-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (23, abaperidone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.

  DOI：

  10.1021/jm9810396
• 作为产物：
  描述：

  2,4-二羟基苯丙酮 在 高氯酸 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 7-(3-chloropropoxy)-3-methyl-chromen-4-one
  参考文献：
  名称：

  7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics. 2. Pharmacological Profile of 7-[3-[4-(6-Fluoro-1,2-benzisoxazol-3-yl)-piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (Abaperidone, FI-8602)

  摘要：

  A series of novel 7-[3-(1-piperidinyl)propoxy]chromenones was synthesized and tested as potential antipsychotics in several in vitro and in vivo assays. The compounds possessed good affinity for Dp receptors, together with a greater affinity for 5-HT2 receptors, a profile which has been proposed as a model for atypical antipsychotics. Several agents also displayed a high potency in the climbing mice assay on oral administration, suggesting a potent antipsychotic effect as compared to reference standards. Compound 23 was selected for fur ther pharmacological evaluation. induction of catalepsy and inhibition of stereotypies weaker than standards, along with a lower increase in serum prolactin levels, were indicative of a potential atypical profile for this compound. From these results, 7-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one (23, abaperidone) has been proposed for clinical evaluation in humans as a potential atypical antipsychotic.

  DOI：

  10.1021/jm9810396

文献信息

• 4-p-fluorobenzoyl-1-piperidinyl-propoxy-chromen-4-one derivatives, their
  申请人：Ferrer Internacional, S.A.

  公开号：US05643927A1

  公开（公告）日：1997-07-01

  The present invention relates to new chromene compounds of the general formula (I): ##STR1## wherein R.sub.1 and R.sub.2 are hydrogen, alkyl having from 1 to 4 carbon atoms, halogen, trifluoromethyl, optionally substituted phenyl, or hydroxymethyl, as well as their pharmaceutically acceptable addition salts. These compounds are useful in the treatment of psychosis and schizophrenia.

  本发明涉及一般式（I）的新的咔咯酮化合物：其中R₁和R₂为氢、具有1至4个碳原子的烷基、卤素、三氟甲基、可选取代的苯基或羟甲基，以及它们的药用可接受的加合物盐。这些化合物在治疗精神病和精神分裂症中有用。
• [EN] 4-(6-FLUORO-1,2-BENZISOXAZOLYL)-1-PIPERIDINYL-PROPOXY-CHROMEN-4-ONE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN THE TREATMENT OF PSYCHOSIS, SCHIZOPHRENIA AND ANXIETY<br/>[FR] DERIVES DE 4-(6-FLUORO-1,2-BENZISOXAZOLYL)-1-PIPERIDINYL-PROPOXY-CHROMEN-4-ONE, LEUR PREPARATION ET LEUR UTILISATION DANS LE TRAITEMENT DES PSYCHOSES, DE LA SCHIZOPHRENIE ET DE L'ANXIETE
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：WO1996032389A1

  公开（公告）日：1996-10-17

  (EN) The present invention relates to 4-(6-fluoro-1,2-benzisoxazolyl)-1-piperidinyl-propoxy-chromen-4-one derivatives having formula (I), wherein R is hydrogen or alkyl having 1 to 4 carbon atoms optionally substituted by hydroxyl, as well as their pharmaceutically acceptable addition salts, which are useful in the treatment of psychosis, schizophrenia and anxiety.(FR) La présente invention décrit des dérivés de 4-(6-fluoro-1,2-benzisoxazolyl)-1-pipéridinyl-propoxy-chromen-4-one de formule (I), dans laquelle R représente hydrogène ou alkyle ayant de 1 à 4 atomes de carbone facultativement substitués par hydroxyle, ainsi que leurs sels d'addition pharmaceutiquement acceptables, utilisés dans le traitement des psychoses, de la schizophrénie et de l'anxiété.

  本发明涉及具有式(I)的4-(6-氟-1,2-苯并异噁唑基)-1-哌啶基-丙氧基-香豆素衍生物，其中R为氢或烷基，烷基含有1至4个碳原子，可选择地被羟基取代，以及它们的药学上可接受的加合物盐，用于治疗精神病、精神分裂症和焦虑症。
• 7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics
  作者：Jordi Bolós、Santiago Gubert、Lluís Anglada、Josep M. Planas、Carme Burgarolas、Josep M. Castelló、Aurelio Sacristán、José A. Ortiz

  DOI：10.1021/jm950894b

  日期：1996.1.1

  Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)- a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.
• 4-P-FLUOROBENZOYL-1-PIPERIDINYL-PROPOXY-CHROMEN-4-ONE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN THE TREATMENT OF PSYCHOSIS AND SCHIZOPHRENIA
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：EP0699197A1

  公开（公告）日：1996-03-06
• 4-(6-FLUORO-1,2-BENZISOXAZOLYL)-1-PIPERIDINYL-PROPOXY-CHROMEN-4-ONE DERIVATIVES, THEIR PREPARATION AND THEIR USE IN THE TREATMENT OF PSYCHOSIS, SCHIZOPHRENIA AND ANXIETY
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：EP0765323A1

  公开（公告）日：1997-04-02