6-Imidazol-1-yl-2-methylsulfanyl-1-propan-2-ylbenzimidazole | 709029-07-2

• 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-Imidazol-1-yl-2-methylsulfanyl-1-propan-2-ylbenzimidazole
• CAS: 709029-07-2
• 化学式: C₁₄H₁₆N₄S
• 分子量: 272.374
• InChiKey: KOQASGBDYLNWHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  60.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-Imidazol-1-yl-2-methylsulfanyl-1-propan-2-ylbenzimidazole 在 间氯过氧苯甲酸 作用下， 以 甲醇 、 氯仿 为溶剂， 生成 6-Imidazol-1-yl-2-methylsulfinyl-1-propan-2-ylbenzimidazole
  参考文献：
  名称：

  Characterization of a new class of selective nonsteroidal progesterone receptor agonists

  摘要：

  The identification of a new series of selective nonsteroidal progesterone receptor (PR) agonists is reported. Using a high-throughput screening assay based on the measurement of transactivation of a mouse mammary tumor virus promoter-driven luciferase reporter (MMTV-Luc) in human breast cancer T47D cells, a benzimidazole-2-thione analog was identified. Compound I showed an apparent EC50 of 53 nM and efficacy of 93% with respect to progesterone. It binds to PR with high affinity (K-i = 89 nM), but had no or very low affinity for other steroid hormone receptors. Structure-activity relationship studies of a series of benzimidazole-2-thione analogs revealed critical positions for high PR binding affinity and transactivation potency as well as receptor selectivity, as exemplified by 25. Compound 25 binds to human PR with high affinity (K-i = 28 nM) and had at least >1000-fold selectivity for PR versus other steroid receptors. Molecular modeling studies suggested that these agonists overlap favorably with progesterone in the ligand-binding domain of PR. In T47D cells, compound 25 acted as a full agonist in the MTV-Luc reporter assay, as well as in the induction of endogenous alkaline phosphatase activity with apparent EC50 values of 4 and 9 nM, respectively. In the immature rat model, compound 25 provided a significant suppression of estrogen-induced endometrium hypertrophy as measured by luminal epithelial height. In contrast, compound 25 was inactive in the luteinizing hormone release assay in young ovariectornized rats. These benzimidazole-2-thione analogs constitute a new series of nonsteroidal PR agonists with an excellent steroid receptor selectivity profile. The differential activities observed in the in vivo progestogenic assays in rat models suggest that these analogs can act as selective PR modulators. (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2003.12.007
• 作为产物：
  描述：

  4-imidazol-1-yl-N²-isopropyl-benzene-1,2-diamine 在 caesium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 6-Imidazol-1-yl-2-methylsulfanyl-1-propan-2-ylbenzimidazole
  参考文献：
  名称：

  Characterization of a new class of selective nonsteroidal progesterone receptor agonists

  摘要：

  The identification of a new series of selective nonsteroidal progesterone receptor (PR) agonists is reported. Using a high-throughput screening assay based on the measurement of transactivation of a mouse mammary tumor virus promoter-driven luciferase reporter (MMTV-Luc) in human breast cancer T47D cells, a benzimidazole-2-thione analog was identified. Compound I showed an apparent EC50 of 53 nM and efficacy of 93% with respect to progesterone. It binds to PR with high affinity (K-i = 89 nM), but had no or very low affinity for other steroid hormone receptors. Structure-activity relationship studies of a series of benzimidazole-2-thione analogs revealed critical positions for high PR binding affinity and transactivation potency as well as receptor selectivity, as exemplified by 25. Compound 25 binds to human PR with high affinity (K-i = 28 nM) and had at least >1000-fold selectivity for PR versus other steroid receptors. Molecular modeling studies suggested that these agonists overlap favorably with progesterone in the ligand-binding domain of PR. In T47D cells, compound 25 acted as a full agonist in the MTV-Luc reporter assay, as well as in the induction of endogenous alkaline phosphatase activity with apparent EC50 values of 4 and 9 nM, respectively. In the immature rat model, compound 25 provided a significant suppression of estrogen-induced endometrium hypertrophy as measured by luminal epithelial height. In contrast, compound 25 was inactive in the luteinizing hormone release assay in young ovariectornized rats. These benzimidazole-2-thione analogs constitute a new series of nonsteroidal PR agonists with an excellent steroid receptor selectivity profile. The differential activities observed in the in vivo progestogenic assays in rat models suggest that these analogs can act as selective PR modulators. (C) 2004 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.steroids.2003.12.007

文献信息

• Characterization of a new class of selective nonsteroidal progesterone receptor agonists
  作者：Yu Dong、Jacques Y Roberge、Zhaoqing Wang、Xiaodong Wang、Joseph Tamasi、Vanessa Dell、Rajasree Golla、James R Corte、Yalei Liu、Tianan Fang、Monique N Anthony、Dora M Schnur、Michele L Agler、John K Dickson、R.Michael Lawrence、Margaret M Prack、Ramakrishna Seethala、Jean H.M Feyen

  DOI：10.1016/j.steroids.2003.12.007

  日期：2004.3

  The identification of a new series of selective nonsteroidal progesterone receptor (PR) agonists is reported. Using a high-throughput screening assay based on the measurement of transactivation of a mouse mammary tumor virus promoter-driven luciferase reporter (MMTV-Luc) in human breast cancer T47D cells, a benzimidazole-2-thione analog was identified. Compound I showed an apparent EC50 of 53 nM and efficacy of 93% with respect to progesterone. It binds to PR with high affinity (K-i = 89 nM), but had no or very low affinity for other steroid hormone receptors. Structure-activity relationship studies of a series of benzimidazole-2-thione analogs revealed critical positions for high PR binding affinity and transactivation potency as well as receptor selectivity, as exemplified by 25. Compound 25 binds to human PR with high affinity (K-i = 28 nM) and had at least >1000-fold selectivity for PR versus other steroid receptors. Molecular modeling studies suggested that these agonists overlap favorably with progesterone in the ligand-binding domain of PR. In T47D cells, compound 25 acted as a full agonist in the MTV-Luc reporter assay, as well as in the induction of endogenous alkaline phosphatase activity with apparent EC50 values of 4 and 9 nM, respectively. In the immature rat model, compound 25 provided a significant suppression of estrogen-induced endometrium hypertrophy as measured by luminal epithelial height. In contrast, compound 25 was inactive in the luteinizing hormone release assay in young ovariectornized rats. These benzimidazole-2-thione analogs constitute a new series of nonsteroidal PR agonists with an excellent steroid receptor selectivity profile. The differential activities observed in the in vivo progestogenic assays in rat models suggest that these analogs can act as selective PR modulators. (C) 2004 Elsevier Inc. All rights reserved.