Diethyl 2,6-dimethyl-4-[6-(2,3,4-trichlorophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-1,4-dihydropyridine-3,5-dicarboxylate | 1308398-25-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: Diethyl 2,6-dimethyl-4-[6-(2,3,4-trichlorophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 1308398-25-5
• 化学式: C₂₄H₂₂Cl₃N₃O₄S
• 分子量: 554.881
• InChiKey: VAMKXEILGAXQEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  乙酰乙酸乙酯 、 6-(2,3,4-Trichlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde 在 ammonium hydroxide 作用下， 以 异丙醇 为溶剂， 以20%的产率得到Diethyl 2,6-dimethyl-4-[6-(2,3,4-trichlorophenyl)imidazo[2,1-b][1,3]thiazol-5-yl]-1,4-dihydropyridine-3,5-dicarboxylate
  参考文献：
  名称：

  Cystic Fibrosis: A New Target for 4-Imidazo[2,1-b]thiazole-1,4-dihydropyridines

  摘要：

  The pharmacology of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel has attracted significant interest in recent years with the aim to search for rational new therapies for diseases caused by CFTR malfunction. Mutations that abolish the function of CFTR cause the life-threatening genetic disease cystic fibrosis (CF). The most common cause of CF is the deletion of phenylalanine 508 (Delta F508) in the CFTR chloride channel. Felodipine, nifedipine, and other antihypertensive 1,4-dihydropyridines (1,4-DHPs) that block L-type Ca2+ channels are also effective potentiators of CFTR gating, able to correct the defective activity of Delta F508 and other CFTR mutants (Mol. Pharmacol. 2005, 68, 1736). For this purpose, we evaluated the ability of the previously and newly synthesized 4-imidazo[2,1-b]thiazoles-1,4-dihydropyridines without vascular activity and inotropic and/or chronotropic cardiac effects (J. Med. Chem. 2008, 51, 1592) to enhance the activity of Delta F508-CFTR. Our studies indicate compounds 17, 18, 20, 21, 38, and 39 as 1,4-DHPs with an interesting profile of activity.

  DOI：

  10.1021/jm200199r

文献信息

• Cystic Fibrosis: A New Target for 4-Imidazo[2,1-<i>b</i>]thiazole-1,4-dihydropyridines
  作者：Roberta Budriesi、Pierfranco Ioan、Alberto Leoni、Nicoletta Pedemonte、Alessandra Locatelli、Matteo Micucci、Alberto Chiarini、Luis J. V. Galietta

  DOI：10.1021/jm200199r

  日期：2011.6.9

  The pharmacology of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel has attracted significant interest in recent years with the aim to search for rational new therapies for diseases caused by CFTR malfunction. Mutations that abolish the function of CFTR cause the life-threatening genetic disease cystic fibrosis (CF). The most common cause of CF is the deletion of phenylalanine 508 (Delta F508) in the CFTR chloride channel. Felodipine, nifedipine, and other antihypertensive 1,4-dihydropyridines (1,4-DHPs) that block L-type Ca2+ channels are also effective potentiators of CFTR gating, able to correct the defective activity of Delta F508 and other CFTR mutants (Mol. Pharmacol. 2005, 68, 1736). For this purpose, we evaluated the ability of the previously and newly synthesized 4-imidazo[2,1-b]thiazoles-1,4-dihydropyridines without vascular activity and inotropic and/or chronotropic cardiac effects (J. Med. Chem. 2008, 51, 1592) to enhance the activity of Delta F508-CFTR. Our studies indicate compounds 17, 18, 20, 21, 38, and 39 as 1,4-DHPs with an interesting profile of activity.