1-(5-Acetyl-thiophen-2-yl)-2-chloro-ethanone | 50460-05-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(5-Acetyl-thiophen-2-yl)-2-chloro-ethanone
• 英文别名: 1-(5-acetylthiophen-2-yl)-2-chloroethanone
• CAS: 50460-05-4
• 化学式: C₈H₇ClO₂S
• 分子量: 202.661
• InChiKey: MFRGLFZRUTXPTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  62.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-乙酰基噻吩 、 氯乙酰氯 在 三氯化铝 作用下， 以 二硫化碳 为溶剂， 反应 1.0h， 以25%的产率得到1-(5-Acetyl-thiophen-2-yl)-2-chloro-ethanone
  参考文献：
  名称：

  噻吩基和苯基α-卤代甲基酮：来自化合物搜索库的糖原合酶激酶（GSK-3beta）的新抑制剂。

  摘要：

  糖原合酶激酶（GSK-3beta）在阿尔茨海默氏病（AD）中起着至关重要的作用。它的抑制是治疗AD的有效方法。在此首封信中，一些噻吩基和苯基α-卤代甲基酮被描述为GSK-3beta的新型非ATP竞争性抑制剂。它们被认为是设计和合成新系列，进行SAR研究，阐明作用机理以及总体上评估其治疗用途的先导化合物。

  DOI：

  10.1021/jm034108b

文献信息

• Thienyl and Phenyl α-Halomethyl Ketones:  New Inhibitors of Glycogen Synthase Kinase (GSK-3β) from a Library of Compound Searching
  作者：Santiago Conde、Daniel I. Pérez、Ana Martínez、Concepción Perez、Francisco J. Moreno

  DOI：10.1021/jm034108b

  日期：2003.10.1

  (AD). Its inhibition is a valid approach to the treatment of AD. In this initial letter, some thienyl and phenyl alpha-halomethyl ketones are described as new non-ATP competitive inhibitors of GSK-3beta. They are considered as lead compounds for designing and synthesizing new series, to carry out SAR studies, clear up the mechanism of action, and, in general, evaluate their therapeutical usefulness.

  糖原合酶激酶（GSK-3beta）在阿尔茨海默氏病（AD）中起着至关重要的作用。它的抑制是治疗AD的有效方法。在此首封信中，一些噻吩基和苯基α-卤代甲基酮被描述为GSK-3beta的新型非ATP竞争性抑制剂。它们被认为是设计和合成新系列，进行SAR研究，阐明作用机理以及总体上评估其治疗用途的先导化合物。
• Compounds and their therapeutic use
  申请人：——

  公开号：US20030199508A1

  公开（公告）日：2003-10-23

  Compounds of formula I: 1 [wherein: X represents —CH═CH—, —CH═CR—, —CR═CR—, —CO—, —O—, —NH—, —NR—, S—, —SO—, —SO 2 —, —CH═N—, —CR═N—, —CH═N(O)—, —CR═N(O)— or any other atom or group of atoms capable of forming a S— or 6-membered heterocyclic ring; Y 1 , Y 2 and Y 3 independently represent hydrogen or halogen; R 1 , R 2 and R 3 are independently represent hydrogen, halogen, hydrocarbyl (—R), hydroxyl (—OH), hydrocarbyloxy (—O—R), mercapto (—SH), hydrocarbylthio (—S—R), hydrocarbylsulfinyl (—SO—R), hydrocarbylsulfonyl (—SO 2 —R), nitro (—NO 2 ), amino (—NH 2 ), hydrocarbylamino (—NHR), bis(hydrocarbyl)amino (—NR 2 ), hydrocarbylcarbonylamino (—NH—CO—R), cyano (—CN), carbamoyl (—CONH 2 ), hydrocarbylcarbarnoyl (—CONHR), bis(hydrocarbyl)carbamoyl (—CONR 2 ), carboxyl (—CO 2 H), hydrocarbyloxycarbonyl (—CO 2 R), formyl (—CHO), hydrocarbylcarbonyl (—COR), hydrocarbylcarbonyloxy (—OCOR), optionally substituted heteroaryl or optionally substituted heterocyclic; and the hydrocarbyl group R is a straight or branched chain hydrocarbyl group selected from alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl and aralkynyl, which may optionally be substituted by one or more substituents, selected from those defined above in relation to R1, R2 and R3]; are of use in the manufacture of a medicament for the treatment including prophylaxis of disease mediated by the activation of GSK-3.

  公式I的化合物：其中：X代表—CH₂CH—、—CH₂CR—、—CR₂CR—、—CO—、—O—、—NH—、—NR—、S—、—SO—、—SO₂—、—CH₂N—、—CR₂N—、—CH₂N(O)—、—CR₂N(O)—或任何其他能够形成S—或6元杂环的原子或原子团；Y₁、Y₂和Y₃独立地代表氢或卤素；R₁、R₂和R₃独立地代表氢、卤素、烃基（—R）、羟基（—OH）、烃氧基（—O—R）、巯基（—SH）、烃硫基（—S—R）、烃基磺基（—SO—R）、烃基磺酰基（—SO₂—R）、硝基（—NO₂）、氨基（—NH₂）、烃基氨基（—NHR）、双（烃基）氨基（—NR₂）、烃基羰基氨基（—NH—CO—R）、氰基（—CN）、氨基甲酰基（—CONH₂）、烃基甲酰胺基（—CONHR）、双（烃基）氨基甲酰基（—CONR₂）、羧基（—CO₂H）、烃氧羰基（—CO₂R）、甲酰基（—CHO）、烃基羰基（—COR）、烃基羰氧基（—OCOR）、可选地取代的杂芳烃或可选地取代的杂环；烃基R为直链或支链烃基，选自烷基、烯基、炔基、芳基、芳基烷基、芳基烯基和芳基炔基，该基团可以选择地被一个或多个取代基取代，所述取代基选自与R₁、R₂和R₃相关定义的那些取代基；用于制造一种药物，用于治疗包括预防GSK-3激活介导的疾病的药物。
• US6747057B2
  申请人：——

  公开号：US6747057B2

  公开（公告）日：2004-06-08
• [EN] COMPOUNDS AND THEIR THERAPEUTIC USE RELATED TO THE PHOSPHORYLATING ACTIVITY OF THE ENZYME GSK-3<br/>[FR] COMPOSES ET UTILISATION THERAPEUTIQUE RELATIVE A L'ACTIVITE DE PHOSPHORYLATION DE L'ENZYME GSK-3
  申请人：CONSEJO SUPERIOR INVESTIGACION

  公开号：WO2003055479A1

  公开（公告）日：2003-07-10

  Compounds of formula (I): wherein: X represents CH=CH-, -CH=CR-, -CR=CR-, -CO-, -O-, -NH-, -NR-, -S-, -SO-, -SO2-, -CH=N-, -CR=N-, -CH=N(O)-, -CR=N(O)- or any other atom or groug of atoms capable of forming a S- or 6- membered heterocyclic ring; Y1, Y2 and Y3 independently represent hydrogen or halogen; R1, R2 and R3 are independently represent hydrogen, halogen, hydrocarbyl (-R), hydroxyl (-OH), hydrocarbyloxy (-O-R), mercapto (-SH), hydrocarbylthio (-S-R), hydrocarbylsulfinyl (-SO-R), hydrocarbylsulfonyl (-SO2-R), nitro (-NO2), amino (-NH2), hydrocarbylamino (-NHR), bis(hydrocarbyl)amino (-NR2), hydrocarbylcarbonylamino (-NH-CO-R), cyano (-CN), carbamoyl (-CONH2), hydrocarbylcarbamoyl (-CONHR), bis(hydrocarbyl)carbamoyl (-CONR2), carboxyl (-CO2H), hydrocarbyloxycarbonyl (-CO2R), formyl (-CHO), hydrocarbylcarbonyl (-COR), hydrocarbylcarbonyloxy (-OCOR), optionally substituted heteroaryl or optionally substituted hetereocyclic; and the hydrocarbyl group R is a straight or branched chain hydrocarbyl group selected from alkyl, alkenyl, alkynyl, aryl, aralkyl, aralkenyl and aralkynyl, which may optionally be subtituted by one or more substituents, selected from those defined above in relation to R1, R2, and R3] ; are of use in the manufacture of a medicament for the treatment including prophylaxis of disease mediated by the activation of GSK-3.
• Thienylhalomethylketones: Irreversible glycogen synthase kinase 3 inhibitors as useful pharmacological tools
  作者：Daniel I. Perez、Santiago Conde、Concepción Pérez、Carmen Gil、Diana Simon、Francisco Wandosell、Francisco J. Moreno、José L. Gelpí、Francisco J. Luque、Ana Martínez

  DOI：10.1016/j.bmc.2009.08.042

  日期：2009.10

  Thienylhalomethylketones, whose chemical, biological, and pharmaceutical data are here reported, are the first irreversible inhibitors of GSK-3 beta described to date. Their inhibitory activity is likely related to the cysteine residue present in the ATP-binding site, which is proposed as a relevant residue for modulation of GSK-3 activity. The good cell permeability of the compounds allows them to be used in different cell models. Overall, the results presented here support the potential use of halomethylketones as pharmacological tools for the study of GSK-3 beta functions and suggest a new mechanism for GSK-3 beta inhibition that may be considered for further drug design. (C) 2009 Elsevier Ltd. All rights reserved.