4-hydroxymethyl-3-((1R)-1-phenyl-ethylamino)-piperidine-1-carboxylic acid tert-butyl ester | 848591-75-3

• 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: 4-hydroxymethyl-3-((1R)-1-phenyl-ethylamino)-piperidine-1-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(hydroxymethyl)-3-[[(1R)-1-phenylethyl]amino]piperidine-1-carboxylate
• CAS: 848591-75-3
• 化学式: C₁₉H₃₀N₂O₃
• 分子量: 334.459
• InChiKey: HGOOISFRTZCVFQ-ODIFPOPNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-hydroxymethyl-3-((1R)-1-phenyl-ethylamino)-piperidine-1-carboxylic acid tert-butyl ester 在 甲基磺酰氯 、 三乙胺 、 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 以42%的产率得到(1S,6R)-8[(1R)-1-phenyl-ethyl]-3,8-diaza-bicyclo[4.2.0]octane-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Substituted diazabicycloalkane derivatives

  摘要：

  式(I)的化合物 Z-Ar 1 —Ar 2 (I) 其中Z是一种二氮杂双环胺，Ar 1 是一个5-或6-成员芳香环，Ar 2 选自未取代或取代的5-或6-成员杂芳基环；未取代或取代的双环杂芳基环；3,4-(亚甲二氧基)苯基；咔唑基；四氢咔唑基；萘基；和苯基；其中苯基在间位或对位上取代有0、1、2或3个取代基。这些化合物在治疗由α7 nAChR配体预防或改善的病症或紊乱中有用。还公开了包含式(I)的化合物的药物组合物以及使用这些化合物和组合物的方法。

  公开号：

  US20050101602A1
• 作为产物：
  描述：

  3-((1R)-1-phenyl-ethylamino)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester 在 lithium aluminium tetrahydride 、 sodium sulfate 作用下， 以 四氢呋喃 为溶剂， 反应 17.0h， 生成 4-hydroxymethyl-3-((1R)-1-phenyl-ethylamino)-piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Substituted diazabicycloakane derivatives

  摘要：

  式(I)的化合物 Z-Ar 1 —Ar 2 (I) 其中Z是一种二氮杂双环胺，Ar 1 是一个5-或6-成员芳香环，Ar 2 从未取代或取代的5-成员杂芳基环；一个未取代或取代的6-成员杂芳基环；3,4-(亚甲二氧基)苯基；和苯基在间位或对位上取代有0、1、2或3个取代基。这些化合物在治疗由α7 nAChR配体预防或改善的病症或紊乱方面是有用的。还公开了包括式(I)的化合物的药物组合物以及使用这些化合物和组合物的方法。

  公开号：

  US20050065178A1

文献信息

• [EN] SUBSTITUTED DIAZABICYCLOALKANE DERIVATIVES AS LIGANDS AT ALPHA 7 NICOTINIC ACETY LCHOLINE RECEPTORS<br/>[FR] DERIVES DE DIAZABICYCLOALCANE SUBSTITUES UTILISES EN TANT QUE LIGANDS AU NIVEAU DES RECEPTEURS ALPHA 7 DE L'ACETYLCHOLINE NICOTINIQUE
  申请人：ABBOTT LAB

  公开号：WO2005028477A1

  公开（公告）日：2005-03-31

  Compounds of formula (I) Z-Ar 1 -Ar 2 wherein Z is a diazabicyclic amine, Ar 1 is a 5- or 6-membered aromatic ring, and Ar 2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.

  化合物的公式（I）为Z-Ar1-Ar2，其中Z是一种二氮杂双环胺，Ar1是一种5-或6-成员的芳香环，而Ar2则选自于未取代或取代的5-或6-成员杂芳基环；未取代或取代的双环杂芳基环；3,4-（亚甲氧基）苯基；咔唑基；四氢咔唑基；萘基；以及苯基；其中苯基在间位或对位上取代有0、1、2或3个取代基。这些化合物在治疗由α7 nAChR配体预防或缓解的疾病或疾病状态中有用。此外，还披露了包含公式（I）化合物的制药组合物以及使用这些化合物和组合物的方法。
• Substituted Diazabicycloalkane Derivates
  申请人：Frost Jennifer M.

  公开号：US20080275048A1

  公开（公告）日：2008-11-06

  Compounds of formula (I) Z-Ar 1 —Ar 2 (I) wherein Z is a diazabicyclic amine, Ar 1 is a 5- or 6-membered aromatic ring, and Ar 2 is selected from the group consisting of an unsubstituted or substituted 5- or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazolyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.

  化合物的公式为（I）Z-Ar1—Ar2（I），其中Z是一种二氮杂双环胺，Ar1是一种5或6成员芳香环，而Ar2则选自未取代或取代的5或6成员杂芳基环；未取代或取代的双环杂芳基环；3,4-（亚甲氧基）苯基；咔唑基；四氢咔唑基；萘基；和苯基；其中苯基在间位或对位上取代有0、1、2或3个取代基。这些化合物在治疗由α7 nAChR配体预防或改善的疾病或疾病方面是有用的。此外，还披露了包含公式（I）化合物的制药组合物以及使用这些化合物和组合物的方法。
• HETEROCYCLIC-CARBONYL-DIAZABICYCLOALKANES AS MODULATORS OF THE NEURONAL NICOTINIC ACETYLCHOLINE ALPHA 4 BETA 2, SUBTYPE RECEPTOR FOR THE TREATMENT OF CNS RELATED DISORDERS
  申请人：Hammond Philip S.

  公开号：US20100144700A1

  公开（公告）日：2010-06-10

  A compound of Formula 1: A-C(O)-Cy, wherein A is a diazabicyclic core, containing 7, 8, or 9 ring atoms, and selected from the following: 2,6-diazabicyclo[3.2.0]heptane; 3,6-diazabicyclo[3.ZO]heptane; 2,7-diazabicyclo[4.2.0]octane; 3,7-diazabicyclo[4.2.0]octane; 3,8-diazabicyclo[4.2.0]octane; 2,7-diazabicyclo[3.3.0]octane; 2,7-diazbicyclo[4.3.0]nonane; 2,8-diazbicyclo[4.3.0]nonane; 3,7-diazabicyclo[4.3.0]nonane; 3,8-diazabicyclo[4.3.0]nonane; 3,9-diazabicyclo[4.3.0]nonane; 2,6-diazabicyclo[3.2.1]octane; 3,6-diazabicyclo[3.2.1]octane; wherein the diazabicycle is attached as a radical to the depicted carbonyl via either one of the two ring nitrogen atoms, such that the carbonyl forms an amide bond with the ring nitrogen; Cy is a heteroaryl group; The compounds exhibit selectivity for, and bind with high affinity to, neuronal nicotinic receptors of the α402 subtype in the central nervous system (CNS). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly CNS disorders. The compounds are believed to: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects, and (iii) when employed in effective amounts, not result in appreciable adverse side effects, namely side effects such as significant Increases in blood pressure and heart rate, significant negative effects upon the gastrointestinal tract, and significant effects upon skeletal muscle.

  化合物的化学式为1：A-C（O）-Cy，其中A是一种含有7、8或9个环原子的二氮杂双环核，可从以下选择：2,6-二氮杂双环[3.2.0]庚烷；3,6-二氮杂双环[3.ZO]庚烷；2,7-二氮杂双环[4.2.0]辛烷；3,7-二氮杂双环[4.2.0]辛烷；3,8-二氮杂双环[4.2.0]辛烷；2,7-二氮杂双环[3.3.0]辛烷；2,7-二氮杂双环[4.3.0]壬烷；2,8-二氮杂双环[4.3.0]壬烷；3,7-二氮杂双环[4.3.0]壬烷；3,8-二氮杂双环[4.3.0]壬烷；3,9-二氮杂双环[4.3.0]壬烷；2,6-二氮杂双环[3.2.1]辛烷；3,6-二氮杂双环[3.2.1]辛烷；其中二氮杂双环通过两个环氮原子之一作为基团连接到所示的羰基上，使羰基与环氮形成酰胺键；Cy是一个杂环芳基基团；这些化合物表现出对中枢神经系统（CNS）的α402亚型的神经元乙酰胆碱受体的选择性和高亲和力。这些化合物和组合物可用于治疗和/或预防各种疾病或疾病，特别是CNS疾病。这些化合物被认为：（i）改变患者的大脑中乙酰胆碱能受体的数量，（ii）表现出神经保护作用，（iii）当以有效剂量使用时，不会产生明显的不良副作用，即明显的血压和心率升高，对胃肠道的明显负面影响以及对骨骼肌的明显影响。
• Substituted diazabicycloalkane derivatives as ligands at alpha 7 nicotinic acetylcholine receptors
  申请人：Abbott Laboratories

  公开号：EP2316836A1

  公开（公告）日：2011-05-04

  Compounds of formula (I) Z-Ar1-Ar2 wherein Z is a diazabicyclic amine, Ar1 is a 5- or 6-membered aromatic ring, and Ar2 is selected from the group consisting of an unsubstituted or substituted 5-or 6-membered heteroaryl ring; unsubstituted or substituted bicyclic heteroaryl ring; 3,4-(methylenedioxy)phenyl; carbazolyl; tetrahydrocarbazoyl; naphthyl; and phenyl; wherein the phenyl is substituted with 0, 1, 2, or 3 substituents in the meta- or para-positions. The compounds are useful in treating conditions or disorders prevented by or ameliorated by α7 nAChR ligands. Also disclosed are pharmaceutical compositions comprising compounds of formula (I) and methods for using such compounds and compositions.

  式(I) Z-Ar1-Ar2 的化合物 其中 Z 是重氮双环胺，Ar1 是 5 或 6 元芳香环，Ar2 选自由未取代或取代的 5 或 6 元杂芳环组成的组；未取代或取代的双环杂芳基环；3,4-（亚甲基二氧基）苯基；咔唑基；四氢咔唑基；萘基；和苯基；其中苯基在元位或对位被 0、1、2 或 3 个取代基取代。这些化合物可用于治疗被 α7 nAChR 配体预防或改善的病症或紊乱。还公开了包含式（I）化合物的药物组合物以及使用此类化合物和组合物的方法。
• SUBSTITUTED DIAZABICYCLOALKANE DERIVATIVES AS LIGANDS AT ALPHA 7 NICOTINIC ACETYLCHOLINE RECEPTORS
  申请人：ABBOTT LABORATORIES

  公开号：EP1664045A1

  公开（公告）日：2006-06-07