羟基伊洛哌酮 | 133454-55-4

• 物质功能分类: 有机原料 - 酮类化合物
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并异恶唑
• 中文名称: 羟基伊洛哌酮
• 中文别名: P88 伊潘立酮代谢物
• 英文名称: 4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-propoxy]-3-methoxy-α-methylbenzenemethanol
• 英文别名: 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanol；4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-α-methylbenzenemethanol；1-(4-{3-[4-(6-fluoro-benzo[d]isoxazol-3-yl)-piperidin-1-yl]-propoxy}-3-methoxy-phenyl)-ethanol；Hydroxy Iloperidone；1-[4-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-methoxyphenyl]ethanol
• CAS: 133454-55-4
• 化学式: C₂₄H₂₉FN₂O₄
• 分子量: 428.504
• InChiKey: SBKZGLWZGZQVHA-UHFFFAOYSA-N

物化性质

• 闪点：
  9℃
• 溶解度：
  氯仿：微溶；甲醇：微溶

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  68
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

代谢

4-[3-[4-(6-氟-1,2-苯并异噁唑-3-基)-1-哌啶基]丙氧基]-3-甲氧基-α-甲基苯甲醇是伊洛哌酮的人体已知代谢物。

4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxy-a-methylbenzene methanol is a known human metabolite of iloperidone.

来源:NORMAN Suspect List Exchange

安全信息

• 储存条件：
  2-8℃

制备方法与用途

生物活性方面，Hydroxy Iloperidone（P88；羟乙醇异丙啶）是Iloperidone的代谢产物。

反应信息

• 作为反应物：
  描述：

  羟基伊洛哌酮 在 氧气 作用下， 反应 10.0h， 以90%的产率得到伊潘立酮
  参考文献：
  名称：

  在无金属和无碱条件下，双（甲氧基丙基）醚促进了O 2将芳族醇氧化为芳族羧酸和芳族酮

  摘要：

  我们描述了一种环保型，实用且操作简单的程序，用于将双（甲氧基丙基）醚促进的芳香族醇氧化成芳香族羧酸和芳香族酮，并以大气中的双氧作为唯一氧化剂。该化学过程是清洁的，具有高转化率和良好的选择性，并且不需要外部引发剂，催化剂，添加剂和碱。该反应的优点在于其易于获得，经济的原料以及出色的官能团耐受性（对酸，碱和氧化剂不稳定的基团）。

  DOI：

  10.1039/c8gc00223a
• 作为产物：
  描述：

  伊潘立酮 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 以67%的产率得到羟基伊洛哌酮
  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

• 1,2-Benzisoxazol-3-yl Compounds
  申请人：Harbeson Scott L.

  公开号：US20080255194A1

  公开（公告）日：2008-10-16

  This invention relates to novel 1,2-benzisoxazol-3-yl compounds, their derivatives, pharmaceutically acceptable salts, solvates, and hydrates thereof. This invention also provides compositions comprising a compound of this invention and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering an antagonist of both dopamine and serotonin receptors.

  本发明涉及新颖的1,2-苯并异噁唑-3-基化合物，它们的衍生物，药学上可接受的盐，溶剂合物和水合物。本发明还提供包含本发明化合物的组合物，并且利用这些组合物在治疗通过给予多巴胺和5-羟色胺受体拮抗剂有益治疗的疾病和症状的方法。
• [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。
• Heteroarylpiperidines and piperazines and their use as antipsychotics and analgetics
  申请人：HOECHST-ROUSSEL PHARMACEUTICALS INCORPORATED

  公开号：EP0957102A1

  公开（公告）日：1999-11-17

  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、吡咯烷和哌嗪类化合物可作为抗精神病和镇痛药剂。这些化合物特别适用于通过向哺乳动物投与其中一种化合物的精神病治疗有效量来治疗精神病。同时，通过向哺乳动物投与其中一种化合物的止痛有效量，这些化合物也可作为止痛药剂。