928134-65-0

• 常用中文名：Osilodrostat (LCI699)
• 常用英文名：Osilodrostat
• CAS号：928134-65-0
• 分子式：C₁₃H₁₀FN₃
• 分子量：227.237
• 相关类别： 信号通路 代谢酶/蛋白酶 盐皮质激素受体
• 发布时间：2017-01-23 08:40:53
• 更新时间：2024-01-06 14:13:47
• Osilodrostat (LCI699) 是人11β-羟化酶和醛固酮合成酶的有效抑制剂,IC50分别值为2.5 和0.7nM。

名称

• 中文名: Osilodrostat
• 英文名: 4-[(5R)-6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzo nitrile
• 英文别名: osilodrostat; 4-(quinolin-3-ylmethyl-amino)-benzenesulfonamide; Novartis LCI699; (R)-4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluorobenzonitrile; UNII-5YL4IQ1078; 4-[(5R)-6,7-Dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluorobenzonitrile; Benzonitrile, 4-[(5R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl]-3-fluoro-; 3-<N-(4'-Amidosulfonylphenyl)aminomethyl>quinoline; 4-((R)-6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-fluoro-benzonitrile

物化性质

• 密度: 1.3±0.1 g/cm3
• 沸点: 433.8±45.0 °C at 760 mmHg
• 分子式: C₁₃H₁₀FN₃
• 分子量: 227.237
• 闪点: 216.2±28.7 °C
• 精确质量: 227.085876
• PSA: 41.61000
• LogP: 1.13
• 外观性状: 粉末
• 蒸汽压: 0.0±1.0 mmHg at 25°C
• 折射率: 1.664
• 储存条件: -20℃

生物活性

• 描述: Osilodrostat (LCI699) 是人11β-羟化酶和醛固酮合成酶的有效抑制剂,IC50分别值为2.5 和0.7nM。
• 相关类别:
  信号通路 >> 代谢酶/蛋白酶 >> 盐皮质激素受体
  研究领域 >> 癌症
  研究领域 >> 炎症/免疫
• 靶点:

  IC50: 2.5 nM (human 11β-hydroxylase), 0.7 nM (aldosterone synthase)[1]

• 体内研究: Osilodrostat和pasireotide单一疗法与垂体和肾上腺,肝脏和卵巢/输卵管的组织学和平均重量的显着变化相关。 Osilodrostat单独与肾上腺皮质肥大和肝细胞肥大有关。结合使用,osilodrostat/pasireotide不会加剧任何靶器官的变化,并改善单药治疗后观察到的肝脏和肾上腺变化。 osilodrostat和pasireotide的Cmax和AUC0-24h以近似剂量成比例的方式增加[1]。 Osilodrostat治疗可降低库欣病患者的尿中游离皮质醇;在第22周,78.9％的患者尿液游离皮质醇正常。用osilodrostat治疗通常耐受性良好[2]。
• 动物实验: 大鼠：将60只雄性大鼠和60只雌性大鼠随机分为单性别组，每日服用帕瑞肽（0.3mg / kg /天，皮下注射），osilodrostat（20mg / kg /天，口服），osilodrostat / pasireotide组合（低剂量，1.5 / 0.03毫克/千克/天;中剂量，5 / 0.1毫克/千克/天;或高剂量，20 / 0.3毫克/千克/天），或载体13周[1]。
• 参考文献:

  [1]. Li L, et al. Osilodrostat (LCI699), a potent 11β-hydroxylase inhibitor, administered in combination with the multireceptor-targeted somatostatin analog pasireotide: A 13-week study in rats. Toxicol Appl Pharmacol. 2015 Aug 1;286(3):224-33.

  [2]. Fleseriu M, et al. Osilodrostat, a potent oral 11β-hydroxylase inhibitor: 22-week, prospective, Phase II study in Cushing's disease. Pituitary. 2016 Apr;19(2):138-48.

合成路线

105942-09-4 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

170572-49-3 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

168632-03-9 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

928136-82-7 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

1472004-27-5 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

1472004-21-9 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

1472004-15-1 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

1567653-71-7 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

928134-37-6 ~% 928134-65-0 928134-66-1

文献：Meredith, Erik L.; Ksander, Gary; Monovich, Lauren G.; Papillon, Julien P. N.; Liu, Qian; Miranda, Karl; Morris, Patrick; Rao, Chang; Burgis, Robin; Capparelli, Michael; Hu, Qi-Ying; Singh, Alok; Rigel, Dean F.; Jeng, Arco Y.; Beil, Michael; Fu, Fumin; Hu, Chii-Whei; Lasala, Daniel ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 12 p. 1203 - 1207

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