6-(3-chloro-4-fluorophenyl)-1-(1-ethylpropyl)-1,3-dihydro-2H-benzimidazol-2-one | 860617-54-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 6-(3-chloro-4-fluorophenyl)-1-(1-ethylpropyl)-1,3-dihydro-2H-benzimidazol-2-one
• CAS: 860617-54-5
• 化学式: C₁₈H₁₈ClFN₂O
• 分子量: 332.805
• InChiKey: OQWJLNMQPPBGPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.15
• 重原子数：
  23.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  37.79
• 氢给体数：
  1.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  6-(3-chloro-4-fluorophenyl)-1-(1-ethylpropyl)-1,3-dihydro-2H-benzimidazol-2-one 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 18.0h， 以55%的产率得到6-(3-chloro-4-fluorophenyl)-1-(1-ethylpropyl)-1,3-dihydro-2H-benzimidazole-2-thione
  参考文献：
  名称：

  5-(3-Cyclopentyl-2-thioxo-2,3-dihydro-1H-benzimidazol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile: A novel, highly potent, selective, and orally active non-steroidal progesterone receptor agonist

  摘要：

  We have recently discovered 5-(3-cyclopentyl-2-thioxo-2,3-dihydro- I H-benzimidazol-5-yl)-1-methyl-1H-pyrrole-2-carbonitrile (14) as a potent, selective, and orally active non-steroidal progesterone receptor (PR) agonist. Compound 14 and its analog 13 possessed sub-nanomolar in vitro potency (EC50 0.1-0.5 nM) in the T47D alkaline phosphatase assay, similar to that of the steroidal PR agonist medroxyprogesterone acetate (MPA). In contrast to MPA, 14 was highly selective (> 500-fold) for the PR over both glucocorticoid and androgen receptors. In the rat uterine decidualization and complement component C3 models, 14 had oral ED50 values of 0.02 and 0.003 mg/kg, respectively, and was from 6- to 20-fold more potent than MPA. In the monkey ovulation inhibition model, compound 14 was also highly efficacious and potent with an oral ED100 of 0.03 mg/kg. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.07.011
• 作为产物：
  描述：

  5-溴-2-氧代-2,3-二氢-1H-苯并[D]咪唑-1-羧酸叔丁酯 在 四(三苯基膦)钯 、 potassium carbonate 、 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 生成 6-(3-chloro-4-fluorophenyl)-1-(1-ethylpropyl)-1,3-dihydro-2H-benzimidazol-2-one
  参考文献：
  名称：

  SAR studies of 6-aryl-1,3-dihydrobenzimidazol-2-ones as progesterone receptor antagonists

  摘要：

  We have previously reported that the aryl substituted benzimidazolones, benzoxazinones, and oxindoles (e.g., 1-3) are progesterone receptor (PR) antagonists and have recently disclosed that the nature of 5- and 6-aryl moieties played a critical role in PR functional activity in the oxindole and benzoxazinone templates. For example, replacing the phenyl group of PR antagonists 2 and 3 with a 5'-cyanopyrrol-2'-yl moiety switched their functional activity to PR agonist activity (2a and 3a). These findings prompted us to examine if there is a similar effect of the 6-aryl moieties on the PR functional activity for the benzimidazolone template. Numerous analogs, such as 5, showed potent PR antagonist activity with about a 10-fold increase in potency as compared to those reported earlier in the same series. More interestingly, pyrrole-containing benzimidazolones 24-27 remained as PR antagonists in contrast to the PR agonist activity switch for oxindole and benzoxazinone scaffolds when a 5'-cyanopyrrol-2'-yl group was installed as a pendant aryl group. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.082