7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-8-chloro-2,3-dihydro-1H-cyclopenta[c]benzopyran-4-one | 1352122-59-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-8-chloro-2,3-dihydro-1H-cyclopenta[c]benzopyran-4-one
• 英文别名: 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-8-chloro-2,3-dihydrocyclopenta[c]chromen-4(1H)-one；7-{4-[4-(3-(6-fluorobenzisoxazole)-1-piperidyl)butoxy]}-8-chloro-2,3-dihydro-1H-cyclopentene[c]benzopyran-4-one；8-chloro-7-[4-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]butoxy]-2,3-dihydro-1H-cyclopenta[c]chromen-4-one
• CAS: 1352122-59-8
• 化学式: C₂₈H₂₈ClFN₂O₄
• 分子量: 510.993
• InChiKey: SNVSEFAOXLDCIZ-UHFFFAOYSA-N

物化性质

• 熔点：
  128-130 °C
• 沸点：
  692.7±55.0 °C(predicted)
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  64.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  己二酸二甲酯 在 aluminum (III) chloride 、 bismuth (III) nitrate pentahydrate 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 生成 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl)piperidin-1-yl)butoxy)-8-chloro-2,3-dihydro-1H-cyclopenta[c]benzopyran-4-one
  参考文献：
  名称：

  Synthesis and evaluation of new coumarin derivatives as potential atypical antipsychotics

  摘要：

  In this paper, we report the synthesis of novel, potential antipsychotic coumarin derivatives combining potent dopamine D-2, D-3 and serotonin 5-HT1A 5-HT(2)A receptors properties. We describe the structure activity relationship that leads us to the promising derivative: 7-(4-(4-(6-fluorobenzo[d]isoxazol-3-yl) piperidin-1-yl)butoxy)-6-methyl-2,3-dihydrocyclopenta[c]chromen-4(1H)-one 27. The unique pharmacological features of compound 27 are a high affinity for dopamine D-2, D-3 and serotonin 5-HT1A, 5-HT2A receptors, together with a low affinity for H-1 receptor (to reduce the risk of obesity under chronic treatment). In animal models, compound 27 inhibited apomorphine-induced climbing and MK-801-induced hyperactivity without observable catalepsy at the highest dose tested. In particular, compound 27 was more potent than clozapine. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.012

文献信息

• ALICYCLIC[C] BENZOPYRONE DERIVATIVES AND USES THEREOF
  申请人：Zhang Guisen

  公开号：US20140171442A1

  公开（公告）日：2014-06-19

  Disclosed are alicyclic[c]benzopyrone derivatives and use thereof. The alicyclic[c]benzopyrone derivatives are compounds represented by formula I or their salts. The present compounds not only significantly improve high activity induced by MK-801, but also effectively improve clambering symptom induced by Apomorphine and do not cause EPS within effective dose. These in vitro targets and in vivo pharmacological models are closely related to diseases of the nervous system caused by dopamine dysfunction, especially schizophrenia. Therefore the present compounds can be used for the treatment of central nervous system diseases, especially schizophrenia. ED 50 is lower and effect is stronger in two animal models i.e. high activity induced by MK-801 and clambering symptom induced by Apomorphine, while ED 50 is higher and therapeutic index is greater in animal models of catalepsy.

  本发明涉及螺环[c]苯并吡喃衍生物及其用途。螺环[c]苯并吡喃衍生物是由式I所表示的化合物或其盐。本化合物不仅显著改善了MK-801引起的高活性，而且有效地改善了阿泼吗啉引起的攀爬症状，并且在有效剂量范围内不会引起EPS。这些体外靶点和体内药理模型与因多巴胺功能障碍引起的神经系统疾病密切相关，特别是精神分裂症。因此，本化合物可用于治疗中枢神经系统疾病，特别是精神分裂症。在两种动物模型即MK-801引起的高活性和阿泼吗啉引起的攀爬症状中，ED50更低，效果更强，而在病理模型的动物模型中，ED50更高，治疗指数更大。
• ALICYCLIC[C]BENZOPYRONE DERIVATIVES AND USES THEREOF
  申请人：Huazhong University of Science and Technology

  公开号：EP2746269A1

  公开（公告）日：2014-06-25

  Disclosed are alicyclic[c]benzopyrone derivatives and use thereof. The alicyclic[c]benzopyrone derivatives are compounds represented by formula I or their salts. The present compounds not only significantly improve high activity induced by MK-801, but also effectively improve clambering symptom induced by Apomorphine and do not cause EPS within effective dose. These in vitro targets and in vivo pharmacological models are closely related to diseases of the nervous system caused by dopamine dysfunction, especially schizophrenia. Therefore the present compounds can be used for the treatment of central nervous system diseases, especially schizophrenia. ED50 is lower and effect is stronger in two animal models i.e. high activity induced by MK-801 and clambering symptom induced by Apomorphine, while ED50 is higher and therapeutic index is greater in animal models of catalepsy.

  公开了脂环族[c]苯并吡喃酮衍生物及其用途。脂环族[c]苯并吡喃酮衍生物为式 I 所代表的化合物或其盐类。本化合物不仅能明显改善 MK-801 诱导的高活性，还能有效改善阿朴吗啡诱发的攀爬症状，并且在有效剂量内不会引起 EPS。这些体外靶点和体内药理模型与多巴胺功能障碍引起的神经系统疾病，尤其是精神分裂症密切相关。因此，本化合物可用于治疗中枢神经系统疾病，尤其是精神分裂症。在两种动物模型（即 MK-801 诱导的高活性和阿朴吗啡诱发的攀爬症状）中，ED50 较低，效果较强；而在催眠动物模型中，ED50 较高，治疗指数较大。
• [EN] ALICYCLIC[C] BENZOPYRONE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE BENZOPYRONE ET DE COMPOSÉS ALICYCLIQUES [C] ET LEURS UTILISATIONS
  申请人：UNIV HUAZHONG SCIENCE TECH

  公开号：WO2013017071A1

  公开（公告）日：2013-02-07

  本发明公开了一种脂环并[c]苯并吡喃酮衍生物及其应用，脂环并[c]苯并吡喃酮衍生物，为式I所示的化合物或其盐。本发明的化合物，既能明显改善MK-801诱导的高活动性，又能有效改善阿扑吗啡诱导的攀爬症状，并且在有效剂量下不引起EPS。由于这些体外作用靶点和体内药理模型与多巴胺功能紊乱导致的神经系统疾病，特别是精神分裂症密切相关，因此本发明涉及的化合物具有治疗中枢神经系统疾病的作用，尤其对精神分裂症有治疗作用。在MK-801诱导高活动性和阿朴吗啡诱导的攀爬的两个动物模型中ED50更小，作用更强，而且在动物僵住症的模型中ED50更大，治疗指数更大。
• ALICYCLIC [C]BENZOPYRONE DERIVATIVES AND USES THEREOF
  申请人：Huazhong University of Science and Technology

  公开号：EP2746269B1

  公开（公告）日：2016-01-20
• US9018213B2
  申请人：——

  公开号：US9018213B2

  公开（公告）日：2015-04-28