3-(1-acetyl-4-piperidinyl)propionyl chloride | 142853-09-6

• 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: 3-(1-acetyl-4-piperidinyl)propionyl chloride
• 英文别名: 3-(1-acetyl-4-piperidinyl)propanoic acid chloride；3-(1-acetyl-4-piperidyl)propionyl chloride；3-(1-acetylpiperidin-4-yl)propionyl chloride；3-(1-acetyl-4-piperidinyl)propionic acid chloride；3-(1-acetyl-4-piperidyl)propionic chloride；3-(1-acetylpiperidin-4-yl)propanoyl chloride
• CAS: 142853-09-6
• 化学式: C₁₀H₁₆ClNO₂
• 分子量: 217.696
• InChiKey: BKCATIMIIHAOEI-UHFFFAOYSA-N

物化性质

• 沸点：
  343.3±15.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(1-acetyl-4-piperidinyl)propionyl chloride 在 盐酸 、 三氯化铝 、 potassium carbonate 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 31.0h， 生成 扎那哌齐
  参考文献：
  名称：

  Central Cholinergic Agents. 6. Synthesis and Evaluation of 3-[1-(Phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)- 1-propanones and Their Analogs as Central Selective Acetylcholinesterase Inhibitors

  摘要：

  In an attempt to find central selective acetylcholinesterase (AChE) inhibitors, 3-[1-(phenyl-methyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanones 9 and their analogs were designed on the basis of our working hypothesis of the enzyme's active site. These compounds were prepared by regioselective Friedel-Crafts acylation of 2,3,4,5-tetrahydro-1H-benzazepines and related nitrogen heterocycles as a key step. Most compounds showed potent inhibitory activities with IC(50)s in the 10-300 nM range. In order to estimate their central selectivities, we examined their effects on the apomorphine-induced circling behavior in rats with unilateral striatal lesions. Among compounds with potent AChE inhibition, 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate (9a, TAK-147) (IC50 of AChE inhibition = 97.7 nM) inhibited the circling behavior at 3 mg/kg po, in which it had no significant effect on peripheral cholinergic effects. This demonstrates that 9a has favorable central selectivity. Furthermore, 9a significantly ameliorated diazepam-induced passive avoidance deficit at 1 mg/kg po. The benzazepine derivative 9a was selected as a candidate for clinical evaluation.

  DOI：

  10.1021/jm00041a007
• 作为产物：
  描述：

  3-哌啶-4-丙酸乙酯 在 氢氧化钾 、 氯化亚砜 作用下， 以 甲醇 为溶剂， 反应 2.17h， 生成 3-(1-acetyl-4-piperidinyl)propionyl chloride
  参考文献：
  名称：

  Central Cholinergic Agents. IV. Synthesis and Acetylcholinesterase Inhibitory Activities of .OMEGA.-(N-Ethyl-N-(phenylmethyl)amino)-1-phenyl-1-alkanones and Their Analogues with Partial Conformational Restriction.

  摘要：

  乙酰胆碱酯酶（AChE）抑制剂的设计是基于酶的活性位点的工作假设。这些化合物被测试了其对AChE的抑制活性，ω-[N-乙基-N-(苯甲基)氨基]-1-苯基-1-烷酮（3）被发现是有效的抑制剂。为了研究构象部分限制对AChE抑制的影响，制备了3的各种类似物。具有强效AChE抑制的化合物进一步评估了其中心选择性：中心作用（在T型迷宫交替任务中改善斯科波拉明诱导的记忆损害的效果）与外周作用的比率。

  DOI：

  10.1248/cpb.41.529

文献信息

• Thermogenic composition and benzazepine thermogenics
  申请人：Takeda Chemical Industries, Inc.

  公开号：US06534496B1

  公开（公告）日：2003-03-18

  The object of the present invention is to provide a prophylactic and/or therapeutic drug for obesity and obesity-associated diseasestor diabetes with a reduced risk for central side effects and high universality in usage. Another object of the present invention is to provide a pharmaceutical composition comprising a compound of the following formula: wherein Ar represents phenyl which may be substituted and/or condensed; n represents an integer of 1 to 10; R represents hydrogen or a hydrocarbon group which may be substituted, which may not be the same in its n occurrences; R may be bound to either Ar or a substituent for Ar; Y represents an amino group which may be subsituted or a nitrogen-containing saturated heterocyclic group which may be substituted, or a salt thereof, which can be used for a thermogenic agent, an antiobesity agent, a lipolytic agent, or a prophylactic and/or treating drug for obesity-associated diseases.

  本发明的目的是提供一种用于肥胖和肥胖相关疾病或糖尿病的预防和/或治疗药物，其具有降低中枢副作用风险和高普遍性的特点。本发明的另一个目的是提供一种包含以下式的化合物的药物组合物： 其中Ar代表可能被取代和/或缩合的苯基；n代表1到10的整数；R代表氢或可能被取代的碳氢基团，在其n次出现时可能不相同；R可以与Ar或Ar的取代物结合；Y代表可能被取代的氨基或可能被取代的含氮饱和杂环基团，或其盐，可用作热原药剂、抗肥胖药剂、脂肪分解药剂，或肥胖相关疾病的预防和/或治疗药物。
• Condensed heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05273974A1

  公开（公告）日：1993-12-28

  A condensed heterocyclic derivative of the formula (I): ##STR1## wherein X is an oxygen atom, a sulfur atom or R.sup.1 --N< wherein R.sup.1 is a hydrogen atom, a hydrocarbon group which may be substituted or an acyl group which may be substituted; R.sup.2 is a hydrogen atom or a hydrocarbon group which may be substituted; ring A is a benzene ring which may be substituted, k is a whole number of 0 to 3; m is a whole number of 1 to 8; and n is a whole number of 1 to 6, or a pharmaceutically acceptable salt thereof exhibiting high colinesterase inhibitory activity, and a method for producing the same.

  化学式（I）的一种缩合杂环衍生物：##STR1##其中X是氧原子、硫原子或R.sup.1--N<，其中R.sup.1是氢原子、可能被取代的碳氢基团或可能被取代的酰基团；R.sup.2是氢原子或可能被取代的碳氢基团；环A是可能被取代的苯环，k是0到3的整数；m是1到8的整数；n是1到6的整数，或其药学上可接受的盐，具有高胆碱酯酶抑制活性，并提供其制备方法。
• Tricyclic condensed heterocyclic compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US05527800A1

  公开（公告）日：1996-06-18

  A novel compound of the formula: ##STR1## wherein Ar represents an optionally substituted tricyclic condensed benzene ring group which includes at least one heterocyclic ring as a component ring; n represents an integer from 2 to 10; R.sup.1 represents H or an optionally substituted hydrocarbon group, which may be different from one another in the repetition of n; and Y represents an optionally substituted 4-piperidinyl, 1-piperazinyl or 4-benzyl-1-piperidinyl group, or a salt thereof, inhibiting excellent cholinesterase inhibitory activity and monoamine reuptake inhibitory activity, thus being useful as therapeutic and/or prophylactic medicaments of senile dementia.

  一种化合物的式子：##STR1## 其中Ar代表一个可选择取代的三环融合苯环基团，其中至少包含一个杂环环作为组成环；n代表一个从2到10的整数；R.sup.1代表H或一个可选择取代的烃基团，可能在n的重复中彼此不同；Y代表一个可选择取代的4-哌啶基、1-哌嗪基或4-苄基-1-哌啶基团，或其盐，抑制优异的胆碱酯酶抑制活性和单胺再摄取抑制活性，因此可用作治疗和/或预防老年性痴呆症的药物。
• Novel acetylcholinesterase inhibitor as increasing agent on rhythmic bladder contractions: SAR of 8-{3-[1-(3-fluorobenzyl)piperidin-4-yl]propanoyl}-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one (TAK-802) and related compounds
  作者：Yuji Ishichi、Mitsuru Sasaki、Masaki Setoh、Tetsuya Tsukamoto、Seiji Miwatashi、Hiroshi Nagabukuro、Satoshi Okanishi、Shigemitsu Imai、Reiko Saikawa、Takayuki Doi、Yuji Ishihara

  DOI：10.1016/j.bmc.2005.01.022

  日期：2005.3

  As part of an on-going investigation to develop an increasing agent on rhythmic bladder contractions, 1-aryl-3-(1-benzylpiperidin-4-yl)propanones were synthesized and examined as noncarbamate acetylcholinesterase (AChE) inhibitors. Among compounds with various aryl groups, 1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one derivative 9c was found to possess a potent AChE inhibition activity with

  作为开发有节奏的膀胱收缩增加剂的正在进行的研究的一部分，合成了1-芳基-3-（1-苄基哌啶-4-基）丙烷，并将其作为非氨基甲酸酯乙酰胆碱酯酶（AChE）抑制剂进行了研究。在具有各种芳基的化合物中，发现1,2,5,6-四氢-4H-吡咯并[3,2,1-ij]喹啉-4-酮衍生物9c具有有效的AChE抑制活性，且具有IC（50 ）值1.3nM。化合物9c可增加豚鼠和大鼠的节律性膀胱收缩，而不会影响基础膀胱内压力，这表明9c可用于治疗逼尿肌功能不足引起的排尿功能障碍。
• Agents and crystals for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20020177593A1

  公开（公告）日：2002-11-28

  Agents for improving potentcy of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action. Particularly, crystals of a tricyclic, condensed, heterocyclic derivative are provided, which possess an excellent action to inhibit acetylcholine esterase and an action to improve the excretory potency of urinary bladder. As an example, crystals of of 8-[3-[1-[(3-fluorophenyl)-methyl]-4-piperidinyl]-1-oxopropyl]-1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-4-one or a salt thereof and pharmaceutical compositions containing them are disclosed.

  改善膀胱功能的药剂，包括一种非卡巴酯类胺化合物，具有乙酰胆碱酯酶抑制作用。特别地，提供了一种三环、紧凑、杂环衍生物的晶体，具有优异的抑制乙酰胆碱酯酶作用和改善膀胱排泄功能的作用。例如，揭示了8-[3-[1-[(3-氟苯基)-甲基]-4-哌啶基]-1-氧代丙基]-1,2,5,6-四氢-4H-吡咯烷[3,2,1-ij]-喹啉-4-酮或其盐和含有它们的药物组合物。