7-(3-chloropropoxy)-2-(hydroxymethyl)chromen-4-one | 220077-05-4

• 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)-2-(hydroxymethyl)chromen-4-one
• 英文别名: 7-(3-chloropropoxy)-2-(hydroxymethyl)-chromen-4-one
• CAS: 220077-05-4
• 化学式: C₁₃H₁₃ClO₄
• 分子量: 268.697
• InChiKey: RGQYWTDKCKZQHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 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)-2-(hydroxymethyl)chromen-4-one 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 18.0h， 以28%的产率得到7-[3-[4-(6-fluorobenzo[d]isoxazole-3-yl)piperidin-1-yl]propoxy]-2-(hydroxymethyl)-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：

  2,4-二羟基苯乙酮 在 盐酸 、 sodium ethanolate 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 生成 7-(3-chloropropoxy)-2-(hydroxymethyl)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

• 7-[(Piperidin-1-YL)-Propoxy]-chromen-4-one derivatives, their preparation and their pharmaceutical use
  申请人：Ferrer Internacional, S.A.

  公开号：US06187793B1

  公开（公告）日：2001-02-13

  7-[3-[4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl]propoxy]-chromen-4-one derivatives having the formula (I): wherein R is hydrogen, CHO, CH2OR2 or COOH; R1 is hydrogen or CH2OH; and R2 is alkyl having 1 to 4 carbon atoms with the proviso that one of substituents R and R1 should be hydrogen, as well as their pharmaceutically acceptable salts. The process for their preparation and the pharmaceutical compositions containing them are also described. The compounds are new and are useful in the treatment of psychosis, schizophrenia and allergy.

  7- [3- [4- (6-氟苯并异噁唑-3-基)哌啶-1-基]丙氧基] -香豆素-4-酮衍生物的化学式（I）：其中R为氢，CHO，CH2OR2或COOH; R1为氢或CH2OH; R2为1至4个碳原子的烷基，但要求取代基R和R1中的一个应为氢，以及它们的药学上可接受的盐。还描述了它们的制备过程和含有它们的药物组合物。这些化合物是新的，可用于治疗精神病、精神分裂症和过敏症。
• [EN] 7-[(PIPERIDIN-1-YL)-PROPOXY]-CHROMEN-4-ONE DERIVATIVES, THEIR PREPARATION AND THEIR PHARMACEUTICAL USE<br/>[FR] DERIVES 7-[(PIPERIDINE-1-YL)-PROPOXY]-CHROMENE-4-ONE, LEUR PREPARATION ET LEUR UTILISATION PHARMACEUTIQUE
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：WO1999035144A1

  公开（公告）日：1999-07-15

  (EN) 7-[3-[4-(6-Fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl]propoxy]-chromen-4-one derivatives having formula (I) wherein R is hydrogen, CHO, CH2OR2 or COOH; R1 is hydrogen or CH2OH; and R2 is alkyl having 1 to 4 carbon atoms with the proviso that one of substituents R and R1 should be hydrogen, as well as their pharmaceutically acceptable salts. The process for their preparation and the pharmaceutical compositions containing them are also described. The compounds are new and are useful in the treatment of psychosis, schizophrenia and allergy.(FR) L'invention concerne des dérivés 7-[3-[4-(6-fluorobenzo[d]isoxazol-3-yl(pipéridine-1-yl)-propoxy]-chromène-4-one, de formule (I), dans laquelle R est hydrogène, CHO, CH2OR2 ou COOH; R1 est hydrogène ou CH2OH; et R2 est alkyle renfermant 1 à 4 atomes de carbone, à condition que R ou R1 soit hydrogène; ainsi que leurs sels pharmaceutiquement acceptables. L'invention concerne également un procédé permettant de les préparer et des compositions pharmaceutiques les contenant. Ces composés sont nouveaux et utiles pour le traitement des psychoses, de la schizophrénie et de l'allergie.

  本发明涉及以下具有以下公式的7-[3-[4-(6-氟苯并吡咯-3-yl)吡啶-1-yl]甲氧基]-二assingene-4-one衍生物，称其为化合物I，其中R为氢、甲基氧、CH2OR2或乙酸根离子；R1为氢或甲氧乙基；R2为1到4个碳原子组成的烷基，其中R和R1中至少一个必须为氢，以及它们的药用可接受的盐。本发明还涉及制备它们的方法以及包含它们的制药组合物。这些化合物是新的且可用于精神分裂症、双相情感障碍和过敏的治疗。
• 7-[(PIPERIDIN-1-YL)- PROPOXY]-CHROMEN-4-ONE DERIVATIVES, THEIR PREPARATION AND THEIR PHARMACEUTICAL USE
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：EP0970076A1

  公开（公告）日：2000-01-12
• US6187793B1
  申请人：——

  公开号：US6187793B1

  公开（公告）日：2001-02-13
• 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)
  作者：Jordi Bolós、Lluís Anglada、Santiago Gubert、Josep M. Planas、Julián Agut、Marta Príncep、Àngels De la Fuente、Aurelio Sacristán、José A. Ortiz

  DOI：10.1021/jm9810396

  日期：1998.12.1

  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.