[6-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)phenyl]propyl}-2-methylphenyl)pyridin-3-yl]acetic acid methyl ester | 1428524-73-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: [6-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)phenyl]propyl}-2-methylphenyl)pyridin-3-yl]acetic acid methyl ester
• CAS: 1428524-73-5
• 化学式: C₃₂H₃₃F₆NO₃
• 分子量: 593.609
• InChiKey: ATMMJRQAASUTFC-CCEZHUSRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.06
• 重原子数：
  42.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.42
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [6-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)phenyl]propyl}-2-methylphenyl)pyridin-3-yl]acetic acid methyl ester 在 sodium hydroxide 、 氯化铵 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 以40%的产率得到[6-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)-phenyl]-propyl}-2-methyl-phenyl)-pyridin-3-yl]-acetic acid
  参考文献：
  名称：

  A series of nonsecosteroidal vitamin D receptor agonists for osteoporosis therapy

  摘要：

  In an extension of our study on gamma hydroxy carboxylic acid analogs, we explored a series of nonsecosteroidal vitamin D receptor (VDR) agonists in which 1,3-diol of 1,25(OH)(2)D-3 had been replaced by aryl acetic acid. These analogs showed very potent activity in vitro compared with 1,25(OH)(2)D-3. An X-ray analysis of 8d showed that the inserted phenyl ring well mimicked the folded methylene linker of the gamma hydroxy carboxylic acid moiety but the carboxylic acid of 8d interacted with VDR in a different manner from gamma hydroxy carboxylic acids. Through our in vivo screening in an osteoporosis rat model using immature rats, we identified a potent active vitamin D-3 analog, compound 7e. In mature rats of the same model, compound 7e also showed good PK profiling and excellent ability to prevent bone mineral density loss without severe hypercalcemia. Our nonsecosteroidal VDR agonist 7e (CH5036249) could be a possible new drug candidate for treating osteoporosis in human. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.042
• 作为产物：
  描述：

  trifluoromethanesulfonic acid 4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-methoxymethoxy-3-trifluoromethyl-1-butenyl)phenyl]propyl}-2-methylphenyl ester 在 1,1'-双(二苯基膦)二茂铁 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium phosphate 、 四(三苯基膦)钯 、 potassium acetate 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 [6-(4-{1-ethyl-1-[3-methyl-4-((E)-4,4,4-trifluoro-3-hydroxy-3-trifluoromethyl-1-butenyl)phenyl]propyl}-2-methylphenyl)pyridin-3-yl]acetic acid methyl ester
  参考文献：
  名称：

  A series of nonsecosteroidal vitamin D receptor agonists for osteoporosis therapy

  摘要：

  In an extension of our study on gamma hydroxy carboxylic acid analogs, we explored a series of nonsecosteroidal vitamin D receptor (VDR) agonists in which 1,3-diol of 1,25(OH)(2)D-3 had been replaced by aryl acetic acid. These analogs showed very potent activity in vitro compared with 1,25(OH)(2)D-3. An X-ray analysis of 8d showed that the inserted phenyl ring well mimicked the folded methylene linker of the gamma hydroxy carboxylic acid moiety but the carboxylic acid of 8d interacted with VDR in a different manner from gamma hydroxy carboxylic acids. Through our in vivo screening in an osteoporosis rat model using immature rats, we identified a potent active vitamin D-3 analog, compound 7e. In mature rats of the same model, compound 7e also showed good PK profiling and excellent ability to prevent bone mineral density loss without severe hypercalcemia. Our nonsecosteroidal VDR agonist 7e (CH5036249) could be a possible new drug candidate for treating osteoporosis in human. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.042