N-(5-propionylthiazol-2-yl)pivalamide | 1067637-92-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(5-propionylthiazol-2-yl)pivalamide
• 英文别名: 2,2-dimethyl-N-(5-propanoyl-1,3-thiazol-2-yl)propanamide
• CAS: 1067637-92-6
• 化学式: C₁₁H₁₆N₂O₂S
• 分子量: 240.326
• InChiKey: SVJGJEULLCASLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(5-propionylthiazol-2-yl)pivalamide 在 pyridinium hydrobromide perbromide 、 氢溴酸 、 溶剂黄146 作用下， 以71%的产率得到N-(5-(2-bromopropanoyl)thiazol-2-yl)pivalamide
  参考文献：
  名称：

  Potent s-cis-Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy

  摘要：

  N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound 15jf) was found previously to correct defective cellular processing of the cystic fibrosis protein Delta F508-CFTR. Eight C4'-C5 C,C-bond-controlling bithiazole analogues of 1 were designed, synthesized, and evaluated to establish that constraining rotation about the bithiazole-tethering has a significant effect on corrector activity. For example, constraining the C4'-C5 bithiazole tether in the s-cis conformation [N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6H-cyclohepta[1,2-d:3,4-d']bithiazole-2'-yl)pivalamide, 29] results in improved corrector activity. Heteroatom placement in the bithaizole core is also critical as evidenced by the decisive loss of corrector activity with s-cis constrained N-(2-(5-chloro-2-methoxyphenylamino)-5,6-dihydro-4H-cyclohepta[1,2-d:3,4-d]bithiazole-2'-yl)pivalamide 33. In addition, computational models were utilized to examine the conformational preferences for select model systems. Following our analysis, the "s-cis-locked" cycloheptathiazolothiazole 29 was found to be the most potent bithiazole corrector, with an IC(50) Of similar to 450 nM.

  DOI：

  10.1021/jm800533c
• 作为产物：
  描述：

  N-[5-(1-hydroxypropyl)-1,3-thiazol-2-yl]-2,2-dimethylpropanamide 在 manganese(IV) oxide 作用下， 以 氯仿 为溶剂， 以0.78 g的产率得到N-(5-propionylthiazol-2-yl)pivalamide
  参考文献：
  名称：

  Potent s-cis-Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy

  摘要：

  N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound 15jf) was found previously to correct defective cellular processing of the cystic fibrosis protein Delta F508-CFTR. Eight C4'-C5 C,C-bond-controlling bithiazole analogues of 1 were designed, synthesized, and evaluated to establish that constraining rotation about the bithiazole-tethering has a significant effect on corrector activity. For example, constraining the C4'-C5 bithiazole tether in the s-cis conformation [N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6H-cyclohepta[1,2-d:3,4-d']bithiazole-2'-yl)pivalamide, 29] results in improved corrector activity. Heteroatom placement in the bithaizole core is also critical as evidenced by the decisive loss of corrector activity with s-cis constrained N-(2-(5-chloro-2-methoxyphenylamino)-5,6-dihydro-4H-cyclohepta[1,2-d:3,4-d]bithiazole-2'-yl)pivalamide 33. In addition, computational models were utilized to examine the conformational preferences for select model systems. Following our analysis, the "s-cis-locked" cycloheptathiazolothiazole 29 was found to be the most potent bithiazole corrector, with an IC(50) Of similar to 450 nM.

  DOI：

  10.1021/jm800533c

文献信息

• Compounds Having Activity in Correcting Mutant-CFTR Processing and Uses Thereof
  申请人：Kurth Mark J.

  公开号：US20100273839A1

  公开（公告）日：2010-10-28

  The invention provides compositions, pharmaceutical preparations and methods for increasing activity of a mutant cystic fibrosis transmembrane conductance regulator protein (mutant-CFTR). The compositions pharmaceutical preparations and methods are useful for the study and treatment of disorders associated with mutant-CFTR, such as cystic fibrosis. The compositions and pharmaceutical preparations of the invention may comprise one or more bithiazole-containing compounds of the invention, or an analog or derivative thereof.

  本发明提供了用于增加突变囊性纤维化跨膜传导调节因子蛋白（突变CFTR）活性的组合物、制药制剂和方法。该组合物、制药制剂和方法可用于突变CFTR相关的疾病的研究和治疗，如囊性纤维化。本发明的组合物和制药制剂可以包含本发明的一种或多种双噻唑含有化合物，或其类似物或衍生物。
• US8389736B2
  申请人：——

  公开号：US8389736B2

  公开（公告）日：2013-03-05
• Potent <i>s-cis</i>-Locked Bithiazole Correctors of ΔF508 Cystic Fibrosis Transmembrane Conductance Regulator Cellular Processing for Cystic Fibrosis Therapy
  作者：Gui Jun Yu、Choong L. Yoo、Baoxue Yang、Michael W. Lodewyk、Liping Meng、Tamer T. El-Idreesy、James C. Fettinger、Dean J. Tantillo、A. S. Verkman、Mark J. Kurth

  DOI：10.1021/jm800533c

  日期：2008.10.9

  N-(5-(2-(5-Chloro-2-methoxyphenylamino)thiazol-4-yl)-4-methylthiazol-2-yl)pivalamide 1 (compound 15jf) was found previously to correct defective cellular processing of the cystic fibrosis protein Delta F508-CFTR. Eight C4'-C5 C,C-bond-controlling bithiazole analogues of 1 were designed, synthesized, and evaluated to establish that constraining rotation about the bithiazole-tethering has a significant effect on corrector activity. For example, constraining the C4'-C5 bithiazole tether in the s-cis conformation [N-(2-(5-chloro-2-methoxyphenylamino)-7,8-dihydro-6H-cyclohepta[1,2-d:3,4-d']bithiazole-2'-yl)pivalamide, 29] results in improved corrector activity. Heteroatom placement in the bithaizole core is also critical as evidenced by the decisive loss of corrector activity with s-cis constrained N-(2-(5-chloro-2-methoxyphenylamino)-5,6-dihydro-4H-cyclohepta[1,2-d:3,4-d]bithiazole-2'-yl)pivalamide 33. In addition, computational models were utilized to examine the conformational preferences for select model systems. Following our analysis, the "s-cis-locked" cycloheptathiazolothiazole 29 was found to be the most potent bithiazole corrector, with an IC(50) Of similar to 450 nM.