6-bromo-1-cyclopentyl-1H-benzo[d]imidazol-2(3H)-one | 860617-67-0

• 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-bromo-1-cyclopentyl-1H-benzo[d]imidazol-2(3H)-one
• 英文别名: 5-bromo-3-cyclopentyl-1H-benzimidazol-2-one
• CAS: 860617-67-0
• 化学式: C₁₂H₁₃BrN₂O
• 分子量: 281.152
• InChiKey: PMJITCIJLOYBJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  6-bromo-1-cyclopentyl-1H-benzo[d]imidazol-2(3H)-one 、 3,4-二氟苯硼酸 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 1.0h， 以54%的产率得到1-cyclopentyl-6-(3,4-difluorophenyl)-1,3-dihydro-2H-benzimidazol-2-one
  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 三苯基膦 、 三氟乙酸 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 6-bromo-1-cyclopentyl-1H-benzo[d]imidazol-2(3H)-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

文献信息

• KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE
  申请人：Icahn School of Medicine at Mount Sinai

  公开号：EP3906028A1

  公开（公告）日：2021-11-10
• [EN] KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS INHIBITEURS DE KINASE, COMPOSITIONS ET PROCÉDÉS D'UTILISATION
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2020142485A1

  公开（公告）日：2020-07-09

  Disclosed herein are kinase inhibitor compounds having structure (I), or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof, where R1, R2, R3, R4, R5, R6, R7, X, Y, Z, and (AA) are as defined herein. Also disclosed are compositions containing the kinase inhibitor compounds, methods of inhibiting activity of a kinase in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.
• [EN] KINASE INHIBITOR COMPOUNDS AND COMPOSITIONS AND METHODS OF USE<br/>[FR] COMPOSÉS INHIBITEURS DE KINASE, COMPOSITIONS ET MÉTHODES D'UTILISATION
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2020142486A1

  公开（公告）日：2020-07-09

  Disclosed are kinase inhibitor compounds having the following structure: (I), or a stereoisomer, pharmaceutically acceptable salt, oxide, or solvate thereof, where R1, R2, R3,R4, R5, R6, N-Ar, X, Y, Z, and AA are as defined herein. Also disclosed are compositions containing the kinase inhibitor compounds, methods of inhibiting activity of a kinase in a cell, methods of increasing cell proliferation in a population of pancreatic beta cells, methods of treating a subject for a condition associated with insufficient insulin secretion, and methods of treating a subject for a neurological disorder.
• SAR studies of 6-aryl-1,3-dihydrobenzimidazol-2-ones as progesterone receptor antagonists
  作者：Eugene A. Terefenko、Jeffrey Kern、Andrew Fensome、Jay Wrobel、Yuan Zhu、Jeffrey Cohen、Richard Winneker、Zhiming Zhang、Puwen Zhang

  DOI：10.1016/j.bmcl.2005.05.082

  日期：2005.8

  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.
• 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
  作者：Puwen Zhang、Eugene Terefenko、Jeffrey Kern、Andrew Fensome、Eugene Trybulski、Ray Unwalla、Jay Wrobel、Susan Lockhead、Yuan Zhu、Jeffrey Cohen、Margaret LaCava、Richard C. Winneker、Zhiming Zhang

  DOI：10.1016/j.bmc.2007.07.011

  日期：2007.10

  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.