2-amino-6,7-dihydro-4H-cyclohepta[d]thiazol-8(5H)-one hydrobromide | 1067638-03-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-amino-6,7-dihydro-4H-cyclohepta[d]thiazol-8(5H)-one hydrobromide
• CAS: 1067638-03-2
• 化学式: BrH*C₈H₁₀N₂OS
• 分子量: 263.158
• InChiKey: GUEQQUBBGLGRJD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.21
• 重原子数：
  13.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.98
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  2-amino-6,7-dihydro-4H-cyclohepta[d]thiazol-8(5H)-one hydrobromide 在 溴 、 溶剂黄146 作用下， 反应 0.5h， 以78%的产率得到2-amino-7-bromo-4,5,6,7-tetrahydro-8H-cyclohepta[d]thiazol-8-one
  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