艾考哌齐 | 145508-78-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 艾考哌齐
• 英文名称: icopezil
• 英文别名: 6,7-dihydro-3-{2-[1-(phenylmethyl)-4-piperidyl]ethyl}-5H-pyrrolo[3,2-f][1,2]benzoxazol-6-one；5,7-dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[4,5-f]-1,2-benzisoxazol-6-one；3-[2-(1-Benzyl-piperidin-4-yl)-ethyl]-5,7-dihydro-1-oxa-2,7-diaza-s-indacene-6-one；5,7-Dihydro-3-[2-[1-benzylpiperidin-4yl]ethyl]-6H-pyrrolo[4,5-f]-1.2-benzisoxazol-6-one；5,7-dihydro-3-[2-[1-(phenyl-methyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one；3-[2-(1-benzylpiperidin-4-yl)ethyl]-5,7-dihydropyrrolo[3,2-f][1,2]benzoxazol-6-one
• CAS: 145508-78-7
• 化学式: C₂₃H₂₅N₃O₂
• 分子量: 375.47
• InChiKey: MTCMTKNMZCPKLX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  58.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  艾考哌齐 以70的产率得到5,7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo-[3,2-f]-1,2-benzisoxazol-6-one maleate
  参考文献：
  名称：

  J. Med. Chem. 1995, 38, 2802-2808

  摘要：

  DOI：
• 作为产物：
  描述：

  5-乙酰基-1,3-二氢-6-羟基-2H-吲哚-2-酮,5-肟乙酸酯 在 吡啶 、 sodium carbonate 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.5h， 生成 艾考哌齐
  参考文献：
  名称：

  5,7-Dihydro-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-6H-pyrrolo[3,2-f]-1,2-benzisoxazol-6-one: A Potent and Centrally-Selective Inhibitor of Acetylcholinesterase

  摘要：

  A series of N-benzylpiperidines (2a-d, 10) with novel isoxazole-containing tricycles has been prepared. This series has shown potent in vitro inhibition of the enzyme acetylcholinesterase (AChE), with IC(50)s = 0.33-3.6 nM. Compound 2a was the most potent inhibitor with an IC50 = 0.33 +/- 0.09 nM. Derivatives 2a-d and 10 displayed weak in vitro inhibition of butyrylcholinesterase (BuChE) with IC(50)s = 600-23 000 nM. The most selective compound was 2a with a BuChE/AChE ratio in excess of 4 orders of magnitude (>10 000). Pyrrolobenzisoxazole 2a also displayed a favorable profile in vivo. In microdialysis experiments, 2a produced a 200% increase in extracellular levels of acetylcholine (ACh) at a dose of 0.4 mg/kg in freely moving, conscious rats. Peripheral side effects (salivation ED(50) = 26 +/- 1.5 mg/kg) and acute lethality (LD(50)[1 h] = 42 mg/kg) were observed at >60-fold higher doses. These data indicate that 2a is an AChE inhibitor with good central selectivity and a favorable margin of safety. Compound 2a, designated as CP-118,954, is currently in clinical development for the treatment of cognitive disorders.

  DOI：

  10.1021/jm00015a002

文献信息

• [EN] BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION<br/>[FR] DÉRIVÉS BIS-HÉTÉROARYLIQUES EN TANT QUE MODULATEURS DE L'AGRÉGATION DES PROTÉINES
  申请人：NEUROPORE THERAPIES INC

  公开号：WO2017020010A1

  公开（公告）日：2017-02-02

  The present invention relates to certain bis-heteroaryl compounds, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto- temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.

  本发明涉及某些双杂环芳基化合物，含有它们的药物组合物，以及使用它们的方法，包括用于预防、逆转、减缓或抑制蛋白聚集的方法，以及治疗与蛋白聚集相关的疾病的方法，包括帕金森病、阿尔茨海默病、路易体病、帕金森病伴痴呆、额颞型痴呆、亨廷顿病、肌萎缩侧索硬化和多系统萎缩等神经退行性疾病，以及包括黑色素瘤在内的癌症。
• [EN] PROCESS FOR THE PREPARATION OF IODIDES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'IODURES
  申请人：TECHNION R & D FOUNDATION LTD

  公开号：WO2011154953A1

  公开（公告）日：2011-12-15

  This invention is directed to a process for the preparation of high yield alkyl or aryl iodide from its corresponding carboxylic acid using N-iodo amides.

  这项发明涉及利用N-碘酰胺从相应的羧酸制备高产量的烷基或芳基碘化物的过程。
• Substituted 4-amino[1,2,4]triazolo[4,3-a] quinoxalines
  申请人：Pfizer Inc.

  公开号：US20040192698A1

  公开（公告）日：2004-09-30

  The present invention provides compounds of formula (I) 1 the prodrugs thereof, and the pharmaceutically acceptable salts of the compounds and prodrugs, wherein R a , R b , R 1 , and R 2 are as defined herein; pharmaceutical compositions thereof; and uses thereof.

  本发明提供了式(I)的化合物 1 的前药，以及所述化合物和前药的药学上可接受的盐，其中R a ，R b ，R 1 和R 2 如本文所定义；其药物组合物；以及其用途。
• [EN] PHENYL-UREA AND PHENYL-CARBAMATE DERIVATIVES AS INHIBITORS OF PROTEIN AGGREGATION<br/>[FR] DÉRIVÉS DE PHÉNYLURÉE ET DE PHÉNYLCARBAMATE COMME INHIBITEURS D'AGRÉGATION DE PROTÉINE
  申请人：NEUROPORE THERAPIES INC

  公开号：WO2013148365A1

  公开（公告）日：2013-10-03

  The present invention relates to certain phenyl-urea and phenyl-carbamate derivatives, pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, and multiple system atrophy.

  本发明涉及某些苯脲和苯氨基甲酸酯衍生物，含有它们的药物组合物以及使用它们的方法，包括用于预防、逆转、减缓或抑制蛋白质聚集的方法，以及用于治疗与蛋白质聚集相关疾病的方法，包括神经退行性疾病，如帕金森病、阿尔茨海默病、路易体病和多系统萎缩。
• [EN] LIPID-SUBSTITUTED AMINO 1,2-AND 1,3-DIOL COMPOUNDS AS MODULATORS OF TLR2 DIMERIZATION<br/>[FR] COMPOSÉS AMINO 1,2-ET 1,3-DIOL SUBSTITUÉS PAR DES LIPIDES EN TANT QUE MODULATEURS DE LA DIMÉRISATION DE TLR2
  申请人：NEUROPORE THERAPIES INC

  公开号：WO2018026866A1

  公开（公告）日：2018-02-08

  The present invention relates to lipid-substituted amino 1,2- and 1,3-diol compounds, pharmaceutical compositions comprising such compounds, and use of such compounds in methods of treatment or in medicaments for treatment of inflammatory diseases and certain neurological disorders that are related to inflammatory signaling processes, including but not limited to misfolded proteins.

  本发明涉及脂质取代的氨基1,2-和1,3-二醇化合物，包括含有此类化合物的药物组合物，以及此类化合物在治疗方法或治疗炎症性疾病和某些与炎症信号传导过程相关的神经系统疾病中的用途，包括但不限于错误折叠蛋白。