1-(4-fluorophenyl)-4-isopropyl-5-trifluoromethanesulfonyloxy-1H-pyrazole-3-carboxylic acid ethyl ester | 1260620-79-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-fluorophenyl)-4-isopropyl-5-trifluoromethanesulfonyloxy-1H-pyrazole-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 1-(4-fluorophenyl)-4-propan-2-yl-5-(trifluoromethylsulfonyloxy)pyrazole-3-carboxylate
• CAS: 1260620-79-8
• 化学式: C₁₆H₁₆F₄N₂O₅S
• 分子量: 424.373
• InChiKey: USPIMXPHVXHICR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.9
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-(4-fluorophenyl)-4-isopropyl-5-trifluoromethanesulfonyloxy-1H-pyrazole-3-carboxylic acid ethyl ester 、 反式-BETA-苯乙烯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 醋酸异丙酯 、 水 、 甲苯 为溶剂， 生成 (E)-1-(4-fluorophenyl)-4-isopropyl-5-styryl-1H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Novel pyrazole-based HMG CoA reductase inhibitors

  摘要：

  描述了作为降胆固醇和降脂血症药物的新化合物和制剂。更具体地，描述了对酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的强效抑制剂。还描述了使用这些化合物和制剂来治疗患有高脂血症、高胆固醇血症、高甘油三酯血症、动脉粥样硬化、阿尔茨海默病、良性前列腺肥大（BPH）、糖尿病和骨质疏松症等疾病的受试者，包括人类的方法。

  公开号：

  US20060111422A1
• 作为产物：
  描述：

  异戊酸乙酯 在 溶剂黄146 作用下， 反应 28.5h， 生成 1-(4-fluorophenyl)-4-isopropyl-5-trifluoromethanesulfonyloxy-1H-pyrazole-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor

  摘要：

  Early process development work toward a promising pyrazole-based HMG-CoA reductase inhibitor is described. PF-03052334-02 (1) was prepared in 14 synthetic steps with a 21% overall yield, highlighted by a modified three-step hydroxypyrazole formation in which the yield was improved from 37% to 73%, a Suzuki/ozonolysis pathway that streamlined the downstream chemistry, and a reversed Wittig olefination strategy that improved the key coupling step from 50% to 95% yield. Multiple process hazards and most chromatography steps were removed, and a highly effective active pharmaceutical ingredient (API) salt formation, purification, and isolation protocol was also developed.

  DOI：

  10.1021/op100268e

文献信息

• NOVEL PYRAZOLE-BASED HMG CoA REDUCTASE INHIBITORS
  申请人：Choi Chulho

  公开号：US20090170852A1

  公开（公告）日：2009-07-02

  Novel compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents are described. More specifically, potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (“HMG CoA reductase”) are described. Methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer's Disease, benign prostatic hypertrophy (BPH), diabetes and osteoporosis are also described.

  本文描述了一种新型化合物和制药组合物，可用作降低胆固醇和脂质的药物。更具体地说，本文描述了一种酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的有效抑制剂。本文还描述了使用这些化合物和组合物治疗患有高脂血症、高胆固醇血症、高三酰甘油血症、动脉粥样硬化、阿尔茨海默病、良性前列腺增生症（BPH）、糖尿病和骨质疏松症等疾病的受试者，包括人类的方法。
• US7446121B2
  申请人：——

  公开号：US7446121B2

  公开（公告）日：2008-11-04
• Novel pyrazole-based HMG CoA reductase inhibitors
  申请人：Choi Chulho

  公开号：US20060111422A1

  公开（公告）日：2006-05-25

  Novel compounds and pharmaceutical compositions useful as hypocholesterolemic and hypolipidemic agents are described. More specifically, potent inhibitors of the enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase (“HMG CoA reductase”) are described. Methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, atherosclerosis, Alzheimer's Disease, benign prostatic hypertrophy (BPH), diabetes and osteoporosis are also described.

  描述了作为降胆固醇和降脂血症药物的新化合物和制剂。更具体地，描述了对酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的强效抑制剂。还描述了使用这些化合物和制剂来治疗患有高脂血症、高胆固醇血症、高甘油三酯血症、动脉粥样硬化、阿尔茨海默病、良性前列腺肥大（BPH）、糖尿病和骨质疏松症等疾病的受试者，包括人类的方法。
• Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor
  作者：Daniel M. Bowles、David C. Boyles、Chulho Choi、Jeffrey A. Pfefferkorn、Stephanie Schuyler、Edward J. Hessler

  DOI：10.1021/op100268e

  日期：2011.1.21

  Early process development work toward a promising pyrazole-based HMG-CoA reductase inhibitor is described. PF-03052334-02 (1) was prepared in 14 synthetic steps with a 21% overall yield, highlighted by a modified three-step hydroxypyrazole formation in which the yield was improved from 37% to 73%, a Suzuki/ozonolysis pathway that streamlined the downstream chemistry, and a reversed Wittig olefination strategy that improved the key coupling step from 50% to 95% yield. Multiple process hazards and most chromatography steps were removed, and a highly effective active pharmaceutical ingredient (API) salt formation, purification, and isolation protocol was also developed.