4-(3-chloro-7,7-dimethyl-5,6,7,8-tetrahydrobenzo[d]imidazo[2,1-b]thiazole-2-carbonyl)-1-cyclopentylpiperazin-2-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-(3-chloro-7,7-dimethyl-5,6,7,8-tetrahydrobenzo[d]imidazo[2,1-b]thiazole-2-carbonyl)-1-cyclopentylpiperazin-2-one
• 英文别名: 4-(3-chloro-7,7-dimethyl-5,6,7,8-tetrahydrobenzo[d]imidazo[2,1-b]thiazol-2-carbonyl)-1-cyclopentylpiperazin-2-one；4-(1-chloro-6,6-dimethyl-7,8-dihydro-5H-imidazo[2,1-b][1,3]benzothiazole-2-carbonyl)-1-cyclopentyl-piperazin-2-one；4-(1-chloro-6,6-dimethyl-7,8-dihydro-5H-imidazo[2,1-b][1,3]benzothiazole-2-carbonyl)-1-cyclopentylpiperazin-2-one
• 化学式: C₂₁H₂₇ClN₄O₂S
• 分子量: 434.99
• InChiKey: IBEKOKAUCMMTPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  86.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3,3-二甲基环己酮 在 N-氯代丁二酰亚胺 、 N-溴代丁二酰亚胺(NBS) 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 45.5h， 生成 4-(3-chloro-7,7-dimethyl-5,6,7,8-tetrahydrobenzo[d]imidazo[2,1-b]thiazole-2-carbonyl)-1-cyclopentylpiperazin-2-one
  参考文献：
  名称：

  Discovery of Imidazo[2,1-b]thiazole HCV NS4B Inhibitors Exhibiting Synergistic Effect with Other Direct-Acting Antiviral Agents

  摘要：

  The design, synthesis, and SAR studies of novel inhibitors of HCV NS4B based on the imidazo[2,1-b]thiazole scaffold were described. Optimization of potency with respect to genotype 1b resulted in the discovery of two potent leads 26f (EC50 = 16 nM) and 28g (EC50 = 31 nM). The resistance profile studies revealed that 26f and 28g targeted HCV NS4B, more precisely the second amphipathic alpha helix of NS4B (4BAH2). Cross-resistance between our 4BAH2 inhibitors and other direct-acting antiviral agents targeting NS3/4A, NS5A, and NS5B was not observed. For the first time, the synergism of a series of combinations based on 4BAH2 inhibitors was evaluated. The results demonstrated that our 4BAH2 inhibitor 26f was synergistic with NS3/4A inhibitor simeprevir, NS5A inhibitor daclatasvir, and NS5B inhibitor sofosbuvir, and it could also reduce the dose of these drugs at almost all effect levels. Our study suggested that favorable effects could be achieved by combining 4BAH2 inhibitors such as 26f with these approved drugs and that new all-oral antiviral combinations based on 4BAH2 inhibitors were worth developing to supplement or even replace current treatment regimens for curing HCV infection.

  DOI：

  10.1021/jm501934n