1-<4-(2-chloroethoxy)-3-methoxyphenyl>ethanone | 3430-03-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-<4-(2-chloroethoxy)-3-methoxyphenyl>ethanone
• 英文别名: 1-[4-(2-Chloroethoxy)-3-methoxyphenyl]ethanone
• CAS: 3430-03-3
• 化学式: C₁₁H₁₃ClO₃
• 分子量: 228.675
• InChiKey: YTKHVPNCKIMSCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-<4-(2-chloroethoxy)-3-methoxyphenyl>ethanone 、 6-氟-3-哌啶-4-基-1,2-苯并异唑盐酸盐 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 1-[4-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethoxy]-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
• 作为产物：
  描述：

  1-溴-2-氯乙烷 、 香草乙酮 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 以42%的产率得到1-<4-(2-chloroethoxy)-3-methoxyphenyl>ethanone
  参考文献：
  名称：

  4-（二芳基羟甲基）-1- [3-（芳氧基）丙基]哌啶及结构相关化合物的合成及抗过敏活性。

  摘要：

  合成了一系列的4-（二芳基羟甲基）-1- [3-（芳氧基）丙基]哌啶，并评估了其抗过敏活性。几种类似物在被动足过敏症（PFA）检测中具有有效活性，PFA检测是一种IgE介导的模型，可用于检测具有抗过敏活性的化合物。特别是1- [4- [3- [4- [双（4-氟苯基）羟甲基] -1-哌啶基]丙氧基] -3-甲氧基苯基]乙酮（1，AHR-5333）比奥沙米特和特非那定在这种测定。

  DOI：

  10.1021/jm00121a022

文献信息

• Arylalkylheterocyclic amines,N-substituted by aryloxyalkyl group in a
  申请人：A. H. Robins Company, Incorporated

  公开号：US04950674A1

  公开（公告）日：1990-08-21

  A method of inhibiting Type 1 allergic responses in a living animal body with substituted heterocyclic amines is disclosed wherein the active agents are expressed generally by the formula which includes certain known and certain known compounds: ##STR1## wherein P is zero, one or two; m is one to six inclusive; A is selected from hydrogen, hydroxy or cyano; d is zero or one; Q is --CH--, CH.sub.2 -- or ##STR2## n is zero or one and when Q is --CH-- and n is one, a double bond is formed with one of the adjacent carbons but not both at the same time, and when n and d are zero at the same time, a double bond is formed between the .alpha. carbon and a carbon of the central heterocyclic amine ring; Ar, D and R are selected from phenyl, substituted phenyl, pyridinyl, thienyl, furanyl or naphthyl and in addition, R may have the values benzyl, substituted benzyl, cycloalkyl or loweralkyl and D may additionally have the values: 2H-1-benzopyran-2-one,4-oxo-4H-1-benzopyran-2-carboxylic acid loweralkyl ester, 2,3-dihydro-4H-1-benzopyran-4-one, 1,4-benzodioxanloweralkyl-2-yl or 1,1'-biphenyl-4-yl and the pharmaceutically acceptable salts thereof.

  揭示了一种利用取代杂环胺抑制活体动物体内的1型过敏反应的方法，其中活性剂通常由以下公式表示：其中P为零、一或二；m为一到六（包括六）；A选自氢、羟基或氰基；d为零或一；Q为--CH--、CH.sub.2--或n为零或一，当Q为--CH--且n为一时，与相邻碳之一形成双键，但不同时与两个相邻碳形成双键；当n和d同时为零时，在中心杂环胺环的α碳和一个碳之间形成双键；Ar、D和R选自苯基、取代苯基、吡啶基、噻吩基、呋喃基或萘基，此外，R可能具有苄基、取代苄基、环烷基或较低烷基的值，D还可能具有以下值：2H-1-苯并吡喃-2-酮、4-氧代-4H-1-苯并吡喃-2-羧酸较低烷基酯、2,3-二氢-4H-1-苯并吡喃-4-酮、1,4-苯并二氧杂环较低烷基-2-基或1,1'-联苯基-4-基，以及其药学上可接受的盐。
• 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。
• Heteroaryl-8-azabicyclo[3,2,1]octanes as antipsychotic agents,
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US05334599A1

  公开（公告）日：1994-08-02

  This invention relates to compounds of the formula ##STR1## where X is --O--, --S-- or --NH--; Y is hydrogen, halogen and loweralkoxy; p is 1 or 2; n is 2, 3 or 4; R is hydrogen, loweralkyl, loweralkoxy, hydroxy, halogen, amino, loweralkylamino, nitro, loweralkylthio, trifiuoromethoxy, cyano, trifiuoromethyl, ##STR2## R.sub.1 is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, carboxyl, loweralkylamino, nitro, loweralkylthio, cyano, and trifiuoromethyl; m is 1 or 2; a pharmaceutically acceptable acid addition salt thereof and, where applicable the geometric and optical isomers and racemic mixtures thereof. The compounds and compositions of this invention are useful as antipsychotic as 5-HT.sub.3 receptor antagonists and as inhibitors of the reuptake of serotonin.

  本发明涉及通式##STR1##所示的化合物，其中X为--O--、--S--或--NH--; Y为氢、卤素和低级烷氧基；p为1或2；n为2、3或4；R为氢、低级烷基、低级烷氧基、羟基、卤素、氨基、低级烷基氨基、硝基、低级烷硫基、三氟甲氧基、氰基、三氟甲基、##STR2##R1为氢、低级烷基、低级烷氧基、卤素、羟基、羧基、低级烷基氨基、硝基、低级烷硫基、氰基和三氟甲基；m为1或2；以及其药学上可接受的酸加成盐，以及在适用情况下，其几何异构体和光学异构体及其外消旋混合物。本发明的化合物和组合物可作为抗精神病药物，作为5-HT3受体拮抗剂，以及作为血清素再摄取抑制剂。
• PROCESS FOR THE PREPARATION OF ILOPERIDONE
  申请人：Vértessy Miklós

  公开号：US20100076196A1

  公开（公告）日：2010-03-25

  A process for the preparation of crystalline 1-[4-[3-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]-ethanone (Iloperidone), which comprises the reaction between 3-[1-(3-chloropropyl)-4-piperidinyl]-6-fluoro-1,2-benzisoxazole and 3-methoxy-4-hydroxy-acetophenone.

  制备结晶1-[4-[3-[4-(6-氟-1,2-苯并异噁唑-3-基)-1-哌啶基]丙氧基]-3-甲氧基苯基]-乙酮（依洛哌酮）的方法，包括3-[1-(3-氯丙基)-4-哌啶基]-6-氟-1,2-苯并异噁唑和3-甲氧基-4-羟基苯乙酮之间的反应。
• 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。