3-[1-(phenylmethyl)-4-piperidinyl)-1-(2,3-dihydroindole-5-yl)-1-propanone | 142852-08-2

• 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-(phenylmethyl)-4-piperidinyl)-1-(2,3-dihydroindole-5-yl)-1-propanone
• 英文别名: 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3-dihydroindol-5-yl]-1-propanone；3-(1-Benzylpiperidin-4-yl)-1-(indolin-5-yl)propan-1-one；3-(1-benzylpiperidin-4-yl)-1-(2,3-dihydro-1H-indol-5-yl)propan-1-one
• CAS: 142852-08-2
• 化学式: C₂₃H₂₈N₂O
• 分子量: 348.488
• InChiKey: RTDPVOSMBHIAJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-[1-(phenylmethyl)-4-piperidinyl)-1-(2,3-dihydroindole-5-yl)-1-propanone 生成 3-[1-(Phenylmethyl)-4-piperidinyl]-1-[1-(pyridin-4-yl)-2,3-dihydroindol-5-yl]-1-propanone Dihydrochloride
  参考文献：
  名称：

  Thermogenic composition and benzazepine thermogenics

  摘要：

  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。

  公开号：

  US06534496B1
• 作为产物：
  描述：

  N-乙酰基吲哚啉 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 3-[1-(phenylmethyl)-4-piperidinyl)-1-(2,3-dihydroindole-5-yl)-1-propanone
  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

文献信息

• 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。
• Agents for improving excretory potency of urinary bladder
  申请人：——

  公开号：US20040116457A1

  公开（公告）日：2004-06-17

  Agents for improving excretory potency of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action.

  改善排泄能力的尿道代理，包括一种非卡巴酯型胺类化合物，具有乙酰胆碱酯酶抑制作用。
• NITROGENOUS FUSED HETEROCYCLE COMPOUNDS, PROCESS FOR THE PREPARATION THEREOF AND AGENTS CONTAINING THE SAME
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1122252A1

  公开（公告）日：2001-08-08

  A nitrogen-containing condensed heterocyclic derivative of the present invention, which is a compound represented by the formula: wherein ring A represents benzene ring optionally having a further substituent, -L-represents -O-, -NR3a-, -S-, -SO-, -SO2-, -SO2NR3a-, -SO2NHCONR3a-, -SO2NHC(=NH)NR3a-, -C(=S)-, or -CONR3a- (wherein R3a and R3b represent independently hydrogen atom, cyano group, hydroxy group, amino group, a C1-6 alkyl group or a C1-6 alkoxy group), n represents an integer of 0 to 6, R is hydrogen atom or a hydrocarbon group optionally having a substituent, and may be different in repetition of n, R1 represents a hydrocarbon group optionally having a substituent or a group represented by the formula: (wherein R7 represents a hydrocarbon group optionally having a substituent), R2 represents hydrogen atom, an acyl group, a hydrocarbon group optionally having a substituent or a heterocyclic group optionally having a substituent, X represents a bond, O, S, SO, SO2 or NR4 (wherein R4 represents hydrogen atom, an acyl group or a hydrocarbon group optionally having a substituent), k and m represent independently an integer of 0 to 5, and 1

  本发明的一种含氮缩合杂环衍生物，它是由式表示的化合物： 其中环 A 代表任选具有另一个取代基的苯环，-L-代表-O-，-NR3a-，-S-，-SO-，-SO2-，-SO2NR3a-，-SO2NHCONR3a-，-SO2NHC(＝NH)NR3a-，-C(＝S)-、 或 -CONR3a-（其中 R3a 和 R3b 分别独立地代表氢原子、氰基、羟基、氨基、C1-6 烷基或 C1-6 烷氧基），n 代表 0 至 6 的整数，R 是氢原子或任选具有取代基的烃基，在重复 n 时可以不同，R1 代表任选具有取代基的烃基或由式表示的基团： (其中 R7 代表任选具有取代基的烃基），R2 代表氢原子、酰基、任选具有取代基的烃基或任选具有取代基的杂环基，X 代表键、O、S、SO、SO2 或 NR4（其中 R4 代表氢原子、其中 R4 代表氢原子、酰基或可选具有取代基的烃基），k 和 m 独立地代表 0 至 5 的整数，且 1
• DRUGS FOR IMPROVING VESICAL EXCRETORY STRENGTH
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1118322A1

  公开（公告）日：2001-07-25

  Agents for improving excretory potency of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action.

  改善膀胱排泄能力的制剂，其中包括一种具有乙酰胆碱酯酶抑制作用的非氨基甲酸酯类胺类化合物。
• Acetylcholinesterase inhibitors for improving excretory potency of urinary bladder
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1604653A1

  公开（公告）日：2005-12-14

  Agents for improving excretory potency of the urinary bladder which comprises an amine compound of non-carbamate-type having an acetylcholinesterase-inhibiting action.

  改善膀胱排泄能力的制剂，其中包括一种具有乙酰胆碱酯酶抑制作用的非氨基甲酸酯类胺类化合物。