1-[2-(4-morpholinyl)-1,3-thiazol-5-yl]ethanone | 84839-77-0

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-[2-(4-morpholinyl)-1,3-thiazol-5-yl]ethanone
• 英文别名: 5-Acetyl-2-morpholinothiazole；1-(2-morpholin-4-yl-1,3-thiazol-5-yl)ethanone
• CAS: 84839-77-0
• 化学式: C₉H₁₂N₂O₂S
• 分子量: 212.272
• InChiKey: ONDPYLJMVWWKFR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  70.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-[2-(4-morpholinyl)-1,3-thiazol-5-yl]ethanone 在 乙酸铵 、 ammonium sulfate 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 6.0h， 生成 N-[4-(3-bromophenyl)-3-cyano-6-(2-morpholin-4-yl-1,3-thiazol-5-yl)pyridin-2-yl]formamidine
  参考文献：
  名称：

  5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine: structure–activity relationships of 7-substituted heteroaryl analogs as non-nucleoside adenosine kinase inhibitors

  摘要：

  4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologic effects of five- and six-membered heterocyclic ring replacements for the pyridine ring in 4. These replacements were found to have interesting effects on in vivo efficacy and genotoxicity as well as in vitro potency. We discovered that the nitrogen in the heterocyclic ring at C(7) is important for the modulation of mutagenic side effects (Ames assay). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.023
• 作为产物：
  描述：

  乙酸酐 、 4-(噻唑-2-基)吗啉 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.5h， 以41%的产率得到1-[2-(4-morpholinyl)-1,3-thiazol-5-yl]ethanone
  参考文献：
  名称：

  5-(3-Bromophenyl)-7-(6-morpholin-4-ylpyridin-3-yl)pyrido[2,3-d]pyrimidin-4-ylamine: structure–activity relationships of 7-substituted heteroaryl analogs as non-nucleoside adenosine kinase inhibitors

  摘要：

  4-Amino-5,7-disubstituted pyridopyrimidines are potent, non-nucleoside inhibitors of adenosine kinase (AK). We recently identified a potent, orally efficacious analog, 4 containing a 7-pyridylmorpholine substituted ring system as the key structural element of this template. In this report, we disclose the pharmacologic effects of five- and six-membered heterocyclic ring replacements for the pyridine ring in 4. These replacements were found to have interesting effects on in vivo efficacy and genotoxicity as well as in vitro potency. We discovered that the nitrogen in the heterocyclic ring at C(7) is important for the modulation of mutagenic side effects (Ames assay). (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.023

文献信息

• On the coupling of aryldiazonium salts with N,N-disubstituted 2-aminothiophenes and some of their carbocyclic and heterocyclic analogues
  作者：Horst Hartmann、Ines Zug

  DOI：10.1039/b006803i

  日期：——

  substitution pattern at C(5), with aryldiazonium salts 1 either at their C(3) or C(5) position yielding the corresponding 3-arylazo-2-morpholinothiophenes 9 or, under elimination of the substituent at C(5), 5-arylazo-2-morpholinothiophenes 10. This reaction contrasts to the behaviour of 5-morpholinothiazoles 8 and dimethylaniline 13 towards the same diazonium salts 1 which are unable to couple with these compounds

  如吗啉代衍生物7所示，根据C（5）处的取代方式，N，N-二取代的2-氨基噻吩对与芳基重氮盐1的C（3）或C（5）位置对产生相应的3 -芳基偶氮-2-吗啉代噻吩9或在消除C（5）取代基的情况下，5-芳基偶氮-2-吗啉代噻吩10。此反应与5-吗啉代噻唑8和二甲基苯胺 如果重氮盐1的C（5）或C（4）位置分别未被H，COOH或CHO取代，则它们不能与这些化合物偶合，而生成13个重氮盐1。
• [EN] 5,7-DISUBSTITUTED-4-AMINOPYRIDO[2,3-D]PYRIMIDINE COMPOUNDS<br/>[FR] COMPOSES DE 4-AMINOPYRIDO[2,3-D]PYRIMIDINE A DISUBSTITUTION 5,7
  申请人：ABBOTT LAB

  公开号：WO2000023444A1

  公开（公告）日：2000-04-27

  A method of inhibiting adenosine kinase by administering one of more compounds of formula (I), wherein R?1, R2, R3 and R4¿ are defined, a pharmaceutical composition comprising a therapeutically effective amount of a compound thereof above in combination with a pharmaceutically acceptable carrier, and a method of treating cerebral ischemia, epilepsy, nociperception, inflammation and sepsis in a mammal in need of such treatment, comprising administering to the mammal a therapeutically effective amount of a compound thereof, a process for preparing said compounds, and compounds having the above formula wherein R?1, R2, R3 and R4¿ are separately defined.

  一种通过给予式(I)中的一个或多个化合物来抑制腺苷激酶的方法，其中R1、R2、R3和R4被定义，以及包含上述化合物的治疗有效量与药学可接受载体组合的制药组合物，以及一种治疗哺乳动物的脑缺血、癫痫、疼痛感知、炎症和败血症的方法，包括给予哺乳动物上述化合物的治疗有效量，制备上述化合物的方法以及具有上述式中R1、R2、R3和R4分别被定义的化合物。
• SPIROCYCLOHEPTANES AS INHIBITORS OF ROCK
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160016914A1

  公开（公告）日：2016-01-21

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically-acceptable salts thereof, wherein all the variables are as defined herein. These compounds are selective ROCK inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating cardiovascular, smooth muscle, oncologic, neuropathologic, autoimmune, fibrotic, and/or inflammatory disorders using the same.

  本发明提供式（I）的化合物：或其立体异构体，互变异构体或药学上可接受的盐，其中所有变量如本文所定义。这些化合物是选择性ROCK抑制剂。本发明还涉及包含这些化合物的制药组合物以及使用它们治疗心血管，平滑肌，肿瘤，神经病理，自身免疫，纤维化和/或炎症性疾病的方法。
• Synthesis and characterisation of N,N-disubstituted 2-amino-5-acylthiophenes and 2-amino-5-acylthiazoles
  作者：Antje Noack、Horst Hartmann

  DOI：10.1016/s0040-4020(02)00083-2

  日期：2002.3

  Starting from halomethyl-ketones 8 and N,N'-persubstituted thioacrylamides 7 or their 2-aza analogues 11 a series of N,N-disubstituted 2-amino-5-acylthiophenes 10 and 2-amino-5-acylthiazoles 12, respectively are available. By starting from 1,3-dichloroacetone and using the same thioacrylamide derivatives 7 and 11 N,N-disubstituted 2-amino-5-(chloroacetyl)thiophenes 13 and 2-amino-5-(chloroacetyl)thiazoles 14 as well as N,N'-persubstituted bis-(2-amino-5-thienyl)ketones 15, 2-amino-5-thienyl-(2-amino-5-thiazolyl)ketones 16, and bis-(2-amino-5-thiazolyl)ketones 17, respectively are available. (C) 2002 Elsevier Science Ltd. All rights reserved.
• RAJAPPA, S.;SUDARSANAM, V.;ADVANI, B. G.;RANE, A. V., PROC. INDIAN ACAD. SCI. CHEM. SCI., 1982, 91, N 5, 445-450
  作者：RAJAPPA, S.、SUDARSANAM, V.、ADVANI, B. G.、RANE, A. V.

  DOI：——

  日期：——