tert-Butyl 4-((6-(2-nitrophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)piperazine-1-carboxylate | 1120341-58-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-Butyl 4-((6-(2-nitrophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[[6-(2-nitrophenyl)imidazo[2,1-b][1,3]thiazol-3-yl]methyl]piperazine-1-carboxylate
• CAS: 1120341-58-3
• 化学式: C₂₁H₂₅N₅O₄S
• 分子量: 443.527
• InChiKey: OQUGCBNQUWSWMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-Butyl 4-((6-(2-nitrophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)piperazine-1-carboxylate 在 吡啶 、 sodium hydrogen sulfide 作用下， 以 甲醇 、 氯仿 、 水 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation

  摘要：

  Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.06.070
• 作为产物：
  描述：

  (6-(2-nitrophenyl)imidazo[2,1-b]thiazol-3-yl)methyl methanesulfonate 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 24.0h， 生成 tert-Butyl 4-((6-(2-nitrophenyl)imidazo[2,1-b]thiazol-3-yl)methyl)piperazine-1-carboxylate
  参考文献：
  名称：

  咪唑并[1,2- b ]噻唑衍生物作为新型SIRT1活化剂的发现

  摘要：

  已显示一系列咪唑并[1,2- b ]噻唑衍生物可激活NAD +依赖性脱乙酰基酶SIRT1，这是治疗各种代谢疾病的潜在新治疗靶标。该系列化合物是从带有恶唑烷吡啶核的高通量筛选命中获得的。水溶性基团可方便地安装在咪唑并[1,2- b ]噻唑环的C-2或C-3位置。可以通过修饰这些咪唑并[1,2- b ]噻唑衍生物的酰胺部分来调节SIRT1酶的活性。该系列中最有效的类似物，即化合物29，已在ob / ob小鼠模型，饮食诱发的肥胖（DIO）小鼠模型和Zucker fa / fa大鼠模型中证明了口服降糖活性。

  DOI：

  10.1021/jm8012954

文献信息

• Sirtuin polymorphisms and methods of use thereof
  申请人：Laakso Markku

  公开号：US20080249103A1

  公开（公告）日：2008-10-09

  Provided herein are methods for diagnosis and prognosis using polymorphic variants of sirtuins. Such polymorphic may be used, for example, to identify subjects that would be responsive to treatment with a sirtuin modulating compound and/or subjects that are suffering from or susceptible to a disease mediated by a sirtuin. Also provided are methods for determining the predictive value of a sirtuin polymorphic variant, methods for evaluating sirtuin modulating compounds, and methods for determining appropriate dosage and/or treatment regimens for subjects having one or more sirtuin polymorphic variants. Screening methods for identifying sirtuin modulating compounds using polymorphic variants of a sirtuin are also provided.

  本文提供了使用sirtuins的多态性变体进行诊断和预后的方法。这种多态性可能被用来识别对sirtuin调节化合物治疗有响应的受试者，以及患有或易受sirtuin介导疾病影响的受试者。还提供了确定sirtuin多态性变体预测价值的方法，评估sirtuin调节化合物的方法，以及确定具有一个或多个sirtuin多态性变体的受试者的适当剂量和/或治疗方案的方法。还提供了使用sirtuin的多态性变体筛选识别sirtuin调节化合物的筛选方法。
• Search for a novel SIRT1 activator: Structural modification of SRT1720 and biological evaluation
  作者：Yuji Matsuya、Yuta Kobayashi、Sayumi Uchida、Yukihiro Itoh、Hideyuki Sawada、Takayoshi Suzuki、Naoki Miyata、Kenji Sugimoto、Naoki Toyooka

  DOI：10.1016/j.bmcl.2013.06.070

  日期：2013.9

  Syntheses and biological evaluation of novel SRT1720 derivatives are described in search for new candidates of SIRT1 activator. Several parts of the SRT1720 structure, including piperazine moiety, quinoxaline ring on the amide group, and position of the amide function, were modified, and the assay results indicated that transfer of the ortho amide-substituent regarding to the imidazo[1,2-b]thiazole core onto the meta position resulted in improvement of SIRT1 activation ability. Modeling analyses of SRT1720 and the most potent derivative bound to model complex of SIRT1 with peptide substrate were also performed. (C) 2013 Elsevier Ltd. All rights reserved.
• Discovery of Imidazo[1,2-<i>b</i>]thiazole Derivatives as Novel SIRT1 Activators
  作者：Chi B. Vu、Jean E. Bemis、Jeremy S. Disch、Pui Yee Ng、Joseph J. Nunes、Jill C. Milne、David P. Carney、Amy V. Lynch、Jesse J. Smith、Siva Lavu、Philip D. Lambert、David J. Gagne、Michael R. Jirousek、Simon Schenk、Jerrold M. Olefsky、Robert B. Perni

  DOI：10.1021/jm8012954

  日期：2009.3.12

  series of imidazo[1,2-b]thiazole derivatives is shown to activate the NAD+-dependent deacetylase SIRT1, a potential new therapeutic target to treat various metabolic disorders. This series of compounds was derived from a high throughput screening hit bearing an oxazolopyridine core. Water-solubilizing groups could be installed conveniently at either the C-2 or C-3 position of the imidazo[1,2-b]thiazole

  已显示一系列咪唑并[1,2- b ]噻唑衍生物可激活NAD +依赖性脱乙酰基酶SIRT1，这是治疗各种代谢疾病的潜在新治疗靶标。该系列化合物是从带有恶唑烷吡啶核的高通量筛选命中获得的。水溶性基团可方便地安装在咪唑并[1,2- b ]噻唑环的C-2或C-3位置。可以通过修饰这些咪唑并[1,2- b ]噻唑衍生物的酰胺部分来调节SIRT1酶的活性。该系列中最有效的类似物，即化合物29，已在ob / ob小鼠模型，饮食诱发的肥胖（DIO）小鼠模型和Zucker fa / fa大鼠模型中证明了口服降糖活性。