1-[4-[3-[4-(5-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-[4-[3-[4-(5-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone
• 英文别名: [4-[3-[4-(5-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone；1-[4-[3-[4-(5-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanone
• 化学式: C₂₄H₂₇FN₂O₄
• 分子量: 426.488
• InChiKey: BNEJDVPNHDRBGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 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：

  4-（3-氯丙基氧基）-3-甲氧基苯乙酮 、 5-氟-3-(4-哌啶基)-1,2-苯并异噁唑 在 potassium carbonate 、 potassium iodide 作用下， 以 乙腈 为溶剂， 反应 8.0h， 以47%的产率得到1-[4-[3-[4-(5-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone
  参考文献：
  名称：

  3-[[(Aryloxy)alkyl]piperidinyl]-1,2-Benzisoxazoles as D2/5-HT2 Antagonists with Potential Atypical Antipsychotic Activity: Antipsychotic Profile of Iloperidone (HP 873)

  摘要：

  A series of 3-[[(aryloxy)alkyl]piperidinyl]-1,2-benzisoxazoles was synthesized and evaluated as potential antipsychotic D-2/5-HT2 antagonists. Most of these compounds showed potent antipsychotic-like activity in an apomorphine-induced climbing mouse paradigm, with many also showing preferential mesolimbic activity, as indicated by their weaker effects in an apomorphine-induced stereotypy model. In receptor binding assays, many displayed a moderate affinity for the D-2 receptor coupled with a significantly greater affinity for the 5-HT2 receptor. a property that has been suggested as necessary for atypicality. From this series, compound 45, 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone (iloperidone, HP 873), was further evaluated in a battery of in vivo and in vitro assays. This compound showed a 300-fold greater potency in inhibition of climbing than in inhibition of stereotypy or induction of catalepsy, and when evaluated chronically in an electrophysiological model, 45 caused a depolarization blockade of dopamine neurons in the A10 area of the rat brain but not in the A9 area. Additionally, it showed positive activity in a social interaction paradigm, suggesting potential efficacy;against asociality, a component of the negative symptoms of schizophrenia. In chronic ex vivo studies, 45, similar to clozapine, caused a down regulation of 5-HT2 receptors but had no effect on the number of D-2 receptors. Compound 45 is currently undergoing clinical evaluation.

  DOI：

  10.1021/jm00007a009

文献信息

• 1-(arylthioalkyl, arylaminoalkyl or arylmethylenealkyl)-4-(heteroaryl)
  申请人：Hoechst Roussel Pharmaceuticals, Inc.

  公开号：US05605913A1

  公开（公告）日：1997-02-25

  Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. the compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. Depot derivatives of the compounds are useful for providing long acting effects of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.

  杂芳基哌啶、吡咯烷和哌嗪作为抗精神病和镇痛剂是有用的。这些化合物特别适用于通过向哺乳动物施用治疗精神病有效量的其中一种化合物来治疗精神病。这些化合物的长效衍生物对于提供这些化合物的长期作用是有用的。通过向哺乳动物施用镇痛有效量的其中一种化合物，这些化合物也作为镇痛剂有用。
• Heteroarylpiperidines, pyrrolidines and piperazines and their use as
  申请人：Hoechst-Roussel Pharmaceuticals, Inc.

  公开号：US05364866A1

  公开（公告）日：1994-11-15

  Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. The compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.

  吡啶基哌啶、吡咯烷和哌嗪等杂环哌啶类化合物可用作抗精神病和镇痛剂。这些化合物特别适用于通过向哺乳动物施用其中一种化合物的抗精神病有效量来治疗精神病。这些化合物也可通过向哺乳动物施用其中一种化合物的镇痛有效量来用作镇痛剂。
• [EN] HETEROARYLPIPERIDINES, PYRROLIDINES AND PIPERAZINES AND THEIR USE AS ANTIPSYCHOTICS AND ANALGETICS
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS, INC.

  公开号：WO1993009102A1

  公开（公告）日：1993-05-13

  (EN) Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. The compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.(FR) Des hétéroarylpiperidines, pyrrolidines et piperazines sont utiles comme agents neuroleptiques et analgésiques. Les composés sont particulièrement utiles dans le traitement de psychoses par administration à un mammifère d'une dose efficace de traitement de psychose d'un des composés. Les composés sont également utiles en tant qu'analgésiques par administration à un mammifère d'une dose efficace calmant la douleur d'un des composés.

  (中文) 杂环芳基哌啶、吡咯烷和哌嗪是作为抗精神病和镇痛剂的有用化合物。这些化合物特别适用于通过向哺乳动物施用其中一种化合物的精神病治疗有效剂量来治疗精神病。这些化合物也可以通过向哺乳动物施用其中一种化合物的止痛有效剂量来作为镇痛剂使用。
• Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analgetics.
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP1052255A1

  公开（公告）日：2000-11-15

  Heteroarylpiperidines, pyrrolidines, and piperazines are useful as antipsychotic and analgesic agents. The compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.

  杂环芳基哌啶、吡咯烷和哌嗪可用作抗精神病和镇痛剂。这些化合物尤其适用于通过向哺乳动物投与化合物的精神病治疗有效量来治疗精神病。这些化合物也可通过向哺乳动物投与化合物的镇痛有效量来用作镇痛剂。
• Heteroarylpiperidines, pyrrolidines and piperazines and their use as antipsychotics and analgetics
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP2311824A1

  公开（公告）日：2011-04-20

  Heteroarylpiperidines, pyrrolidines, and piperazines of the formula wherein X is -O-, -S-, -NH-, or -N(R2)- R2 is selected from the group consisting of lower alkyl, aryl lower alkyl, aryl, cycloalkyl, aroyl, alkanoyl, alkoxycarbonyl and phenylsulfonyl groups; p is 1 or 2 Y is hydrogen, lower alkyl, hydroxy, chlorine, fluorine, bromine, iodine, lower alkoxy, trifluoromethyl, nitro, or amino; Q1 is selected from the group consisting of: and where Z is are useful as antipsychotic and analgesic agents. The compounds are especially useful for treating psychoses by administering to a mammal a psychoses-treating effective amount of one of the compounds. Depot derivatives of the compounds are useful for providing long acting effects of the compounds. The compounds are also useful as analgesics by administering a pain-relieving effective amount of one of the compounds to a mammal.

  式中X为-O-，-S-，-NH-或-N（R2）-，R2选自下列组：低烷基，芳基低烷基，芳基，环烷基，芳香酰基，烷酰基，烷氧羰基和苯基磺酰基基团；p为1或2；Y为氢，低烷基，羟基，氯，氟，溴，碘，低烷氧基，三氟甲基，硝基或氨基；Q1选自下列组：其中Z为，本发明化合物作为抗精神病和镇痛剂具有应用价值。该化合物特别适用于通过向哺乳动物施用化合物的精神病治疗有效量来治疗精神病。该化合物的沉积物衍生物可用于提供化合物的长效作用。该化合物也可通过向哺乳动物施用缓解疼痛的有效量的化合物来用作镇痛剂。