[5-benzylcarbamoyl-2-(4-fluorophenyl)-4-isopropyl-2H-pyrazol-3-ylmethyl]triphenylphosphonium bromide | 887703-80-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [5-benzylcarbamoyl-2-(4-fluorophenyl)-4-isopropyl-2H-pyrazol-3-ylmethyl]triphenylphosphonium bromide
• 英文别名: [5-benzylcarbamoyl-2-(4-fluoro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethyl]-triphenyl-phosphonium bromide；[5-(benzylcarbamoyl)-2-(4-fluorophenyl)-4-propan-2-ylpyrazol-3-yl]methyl-triphenylphosphanium;bromide
• CAS: 887703-80-2
• 化学式: Br*C₃₉H₃₆FN₃OP
• 分子量: 692.611
• InChiKey: RBFXDNVFJYVOKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.56
• 重原子数：
  46
• 可旋转键数：
  10
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  46.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [5-benzylcarbamoyl-2-(4-fluorophenyl)-4-isopropyl-2H-pyrazol-3-ylmethyl]triphenylphosphonium bromide 、 (4R-cis)-6-醛基-2,2-二甲基-1,3-二氧己环-4-乙酸叔丁酯 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 0.08h， 生成 (6-{2-[5-benzylcarbamoyl-2-(4-fluorophenyl)-4-isopropyl-2H-pyrazol-3-yl]vinyl}-2,2-dimethyl-[1R,3R]dioxan-4-yl)acetic acid tert-butyl ester
  参考文献：
  名称：

  Substituted Pyrazoles as Hepatoselective HMG-CoA Reductase Inhibitors: Discovery of (3R,5R)-7-[2-(4-Fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2H-pyrazol-3-yl]-3,5-dihydroxyheptanoic Acid (PF-3052334) as a Candidate for the Treatment of Hypercholesterolemia

  摘要：

  In light of accumulating evidence that aggressive LDL-lowering therapy may offer increased protection against coronary heart disease, we undertook the design and synthesis of a novel series of HMG-CoA reductase inhibitors based upon a substituted pyrazole template. Optimizing this series using both structure-based design and molecular property considerations afforded a class of highly efficacious and hepatoselective inhibitors resulting in the identification of (3 R,5 R)-7-[2-(4-fluoro-phenyl)-4-isopropyl-5-(4-methyl-benzylcarbamoyl)-2 H-pyrazol-3-yl]-3,5-dihydroxy-heptanoic (PF-3052334) as a candidate for the treatment of hypercholesterolemia.

  DOI：

  10.1021/jm070849r
• 作为产物：
  描述：

  1-(4-fluorophenyl)-5-hydroxymethyl-4-isopropyl-1H-pyrazole-3-carboxylic acid benzylamide 、 三苯基膦氢溴酸盐 以 乙腈 为溶剂， 反应 36.0h， 以to provide [5-benzylcarbamoyl-2-(4-fluoro-phenyl)-4-isopropyl-2H-pyrazol-3-ylmethyl]-triphenyl-phosphonium bromide (0.977 g, 98%) in sufficient purity for use in the next step的产率得到[5-benzylcarbamoyl-2-(4-fluorophenyl)-4-isopropyl-2H-pyrazol-3-ylmethyl]triphenylphosphonium bromide
  参考文献：
  名称：

  Pyrazole-based HMG CoA reductase inhibitors

  摘要：

  本文描述了作为降低胆固醇和脂质的药物的新化合物和制药组合物。更具体地，描述了强效的酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的抑制剂。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、动脉硬化、阿尔茨海默病、良性前列腺肥大、糖尿病和骨质疏松症等病症的受试者，包括人类的方法。

  公开号：

  US07446121B2

文献信息

• 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。
• Pyrazole-based HMG CoA reductase inhibitors
  申请人：Pfizer Inc.

  公开号：US07446121B2

  公开（公告）日：2008-11-04

  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.

  本文描述了作为降低胆固醇和脂质的药物的新化合物和制药组合物。更具体地，描述了强效的酶3-羟基-3-甲基戊二酰辅酶A还原酶（“HMG CoA还原酶”）的抑制剂。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、动脉硬化、阿尔茨海默病、良性前列腺肥大、糖尿病和骨质疏松症等病症的受试者，包括人类的方法。
• 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。
• 7-(2H-PYRAZOL-3-YL)-3,5-DIHYDROXY-HEPTANOIC ACID DERIVATIVES AS HMG CO-A REDUCTASE INHIBITORS FOR THE TREATMENT OF LIPIDEMIA
  申请人：Warner-Lambert Company LLC

  公开号：EP1819681B1

  公开（公告）日：2009-08-12
• US7446121B2
  申请人：——

  公开号：US7446121B2

  公开（公告）日：2008-11-04