tert-butyl 4-((4-fluorophenyl)(methoxy)methyl)piperidine-1-carboxylate | 160296-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-((4-fluorophenyl)(methoxy)methyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[(4-fluorophenyl)-methoxymethyl]piperidine-1-carboxylate
• CAS: 160296-42-4
• 化学式: C₁₈H₂₆FNO₃
• 分子量: 323.408
• InChiKey: JXWLYCRGIKFGKS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((4-fluorophenyl)(methoxy)methyl)piperidine-1-carboxylate 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 1.0h， 以69%的产率得到4-[1-(4-fluorophenyl)-1-methoxymethyl]piperidine
  参考文献：
  名称：

  7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics

  摘要：

  Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)- a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.

  DOI：

  10.1021/jm950894b
• 作为产物：
  描述：

  4-(4-氟苯甲酰基)哌啶-1-甲酸叔丁酯 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 18.5h， 生成 tert-butyl 4-((4-fluorophenyl)(methoxy)methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  7-[3-(1-Piperidinyl)propoxy]chromenones as Potential Atypical Antipsychotics

  摘要：

  Compound 1 (1-benzyl-3-methyl-4-[4-(4-fluorophenyl)- a synthetic intermediate identified as a potential atypical antipsychotic, was selected as the starting point for pharmacological improvement. From 1, sequential structural variations were conducted in order to improve its potency and oral bioavailability. These variations included a series of piperazine, ethanediamine, and piperidine derivatives. The piperidine series afforded some orally potent compounds in the inhibition of apomorphine-induced climbing and hyperactivity in mice, which are regarded as behavioral models predictive of antipsychotic efficacy. Further optimization of these structures led to the highly potent 7-[3-(1-piperidinyl)propoxy]chromenones. Inhibition of stereotypies and induction of catalepsy in rats at doses substantially higher than required for inhibition of climbing suggest an atypical antipsychotic profile, which is assumed to predict a reduced induction of extrapyramidal side effects in humans.

  DOI：

  10.1021/jm950894b

文献信息

• [EN] PIPERIDINYL- AND PIPERAZINYL-SUBSTITUTED HETEROAROMATIC CARBOXAMIDES AS MODULATORS OF GPR6<br/>[FR] CARBOXAMIDES HÉTÉROAROMATIQUES SUBSTITUÉS PAR PIPÉRIDINYLE ET PIPÉRAZINYLE EN TANT QUE MODULATEURS DE GPR6
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2018183145A1

  公开（公告）日：2018-10-04

  Disclosed are compounds of Formula 1 and pharmaceutically acceptable salts thereof, wherein L, R4, R5, R8, R10, R11, X1, X2, X3, X9, X12, and Z are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with GPR6.

  本公开涉及公式1的化合物及其药用可接受的盐，其中L、R4、R5、R8、R10、R11、X1、X2、X3、X9、X12和Z在规范中定义。本公开还涉及制备公式1化合物的材料和方法，包含它们的药物组合物，以及它们用于治疗与GPR6相关的疾病、紊乱和症状的用途。
• 4-(4-FLUOROPHENYLMETHYL)-PIPERIDINES HAVING SIGMA AND D2-RECEPTOR AFFINITY
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：EP0651744A1

  公开（公告）日：1995-05-10
• PIPERIDINYL- AND PIPERAZINYL-SUBSTITUTED HETEROAROMATIC CARBOXAMIDES AS MODULATORS OF GPR6
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US20200375969A1

  公开（公告）日：2020-12-03

  Disclosed are compounds of Formula 1 and pharmaceutically acceptable salts thereof, wherein L, R 4 , R 5 , R 8 , R 10 , R 11 , X 1 , X 2 , X 3 , X 9 , X 12 , and Z are defined in the specification. This disclosure also relates to materials and methods for preparing compounds of Formula 1, to pharmaceutical compositions which contain them, and to their use for treating diseases, disorders, and conditions associated with GPR6.
• OXAZINE MONOACYLGLYCEROL LIPASE (MAGL) INHIBITORS
  申请人：Hoffmann-La Roche Inc.

  公开号：US20210107920A1

  公开（公告）日：2021-04-15

  The invention provides new heterocyclic compounds having the general formula (Ic) wherein A, L, X, m, n and R 20 to R 23 are as described herein, compositions including the compounds, processes of manufacturing the compounds and methods of using the compounds.
• [EN] 4-(4-FLUOROPHENYLMETHYL)-PIPERIDINES HAVING SIGMA AND D2-RECEPTOR AFFINITY<br/>[FR] 4-(4-FLUOROPHENYLMETHYL)-PIPERIDINES PRESENTANT UNE AFFINITE AVEC LES RECEPTEURS SIGMA ET D2
  申请人：FERRER INTERNACIONAL, S.A.

  公开号：WO1994026712A1

  公开（公告）日：1994-11-24

  (EN) The present invention relates to 1,4-disubstituted piperidine derivatives of general formula (I) wherein X is hydroxymethylene or methoxymethylene, Y is a 3-membered methylene sequence and R is a p-fluorophenyl group, as well as their pharmaceutically acceptable addition salts. These compounds are useful for treating sigma receptor-related nervous system diseases.(FR) L'invention concerne des dérivés de 1,4-pipéridine bisubstitués de formule générale (I) dans laquelle X représente hydroxyméthylène ou méthoxyméthylène, Y représente une séquence de méthylène à 3 éléments et R représente un groupe p-fluorophényle, ainsi que leurs sels d'addition pharmaceutiquement acceptables. Ces composés sont utiles pour le traitement de maladies du système nerveux liées aux récepteurs sigma.