7-(3-chloropropoxy)-3-(hydroxymethyl)chromen-4-one | 172739-49-0

• 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-(hydroxymethyl)chromen-4-one
• CAS: 172739-49-0
• 化学式: C₁₃H₁₃ClO₄
• 分子量: 268.697
• InChiKey: DSIBXRJGMYMHBC-UHFFFAOYSA-N

物化性质

• 沸点：
  467.1±45.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

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-(hydroxymethyl)chromen-4-one 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以37%的产率得到阿巴哌酮
  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：

  1-[4-(3-氯丙氧基)-2-羟基苯基]乙酮 在 sodium methylate 、 sodium acetate 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 2.5h， 生成 7-(3-chloropropoxy)-3-(hydroxymethyl)chromen-4-one
  参考文献：
  名称：

  3-（羟甲基）-4 H -chromen-4-ones的高效合成新方法

  摘要：

  报道了各种取代的3-（羟甲基）-4 H-铬烯-4-酮的有效和通用的合成。通过将前体2-羟基-4-二氢呋喃酮进行羟甲基化，然后进行酸脱水来制备化合物。

  DOI：

  10.1002/jhet.5570370529

文献信息

• 4-(6-fluoro-1,2-benzisoxazolyl)-1
  申请人：Ferrer Internacional, S.A.

  公开号：US05736558A1

  公开（公告）日：1998-04-07

  The present invention relates to 4-(6-fluoro-1,2-benzisoxazolyl)-1-piperidinyl-propoxy-chromen-4-one derivatives having the formula (I): ##STR1## 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.

  本发明涉及具有以下结构的4-(6-氟-1,2-苯并异噁唑基)-1-哌啶基-丙氧基-香豆素-4-酮衍生物（I）：##STR1## 其中R是氢或1至4个碳原子的烷基，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。
• [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.
• J. Med. Chem. 1996, 39, 2962-2970
  作者：

  DOI：——

  日期：——
• J. Med. Chem. 1998, 41, 5402-5409
  作者：

  DOI：——

  日期：——