3-(acetoxymethyl)-2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazole | 144148-33-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(acetoxymethyl)-2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazole
• 英文别名: 3-Acetoxymethyl-2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazole；[2-(4-fluorophenyl)-4,5,6,7-tetrahydroindazol-3-yl]methyl acetate
• CAS: 144148-33-4
• 化学式: C₁₆H₁₇FN₂O₂
• 分子量: 288.322
• InChiKey: OSXZIWUVHXKVND-UHFFFAOYSA-N

物化性质

• 沸点：
  399.5±42.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(acetoxymethyl)-2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazole 在 manganese(IV) oxide 、 sodium hydroxide 、 sodium hydride 、 二异丁基氢化铝 、 pyridinium chlorochromate 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 、 苯 为溶剂， 反应 7.0h， 生成 (E)-3-[2-(4-fluorophenyl)-4,5,6,7-tetrahydroindazol-3-yl]prop-2-enal
  参考文献：
  名称：

  HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts

  摘要：

  Compounds comprising a series of 7-[2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-3,5-dihydroxy-6-heptenoic acid sodium salts (18) were synthesized and tested for their ability to inhibit HMG-CoA reductase in a partially purified enzyme preparation and cholesterol biosynthesis from acetate in cultured HEP-G2 cells. Changing the size of the saturated ring of the tetrahydroindazole nucleus did not improve potency, but incorporation of substituents at the 7-position resulted in up to 1700-fold improvement in inhibitory potency. Structure-activity studies revealed that the most potent compounds possess a substituted benzyl group at the 7-position, with a preference for steric bulk at the para position of the benzene ring. The most potent enzyme inhibitor (18t, IC50 = 3.0 nM) is approximately 3-fold more potent than lovastatin sodium salt (2). The most potent cholesterol biosynthesis inhibitor in HEP-G2 cells (18q, IC50 = 0.078 muM) is slightly less potent than 2 (sodium salt). Molecular modeling studies suggested that, when compared to the parent compound (18b) lacking the appropriate 7-substituent, 18t overlaps better with 2 and literature inhibitors 5 and 6 in a hydrophobic binding region adjacent to the enzyme active site.

  DOI：

  10.1021/jm00075a024
• 作为产物：
  描述：

  环己酮 在 吗啉 、 三乙胺 作用下， 以 乙醇 、 苯 为溶剂， 反应 10.0h， 生成 3-(acetoxymethyl)-2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazole
  参考文献：
  名称：

  HMG-CoA reductase inhibitors: design, synthesis, and biological activity of tetrahydroindazole-substituted 3,5-dihydroxy-6-heptenoic acid sodium salts

  摘要：

  Compounds comprising a series of 7-[2-(4-fluorophenyl)-4,5,6,7-tetrahydro-2H-indazol-3-yl]-3,5-dihydroxy-6-heptenoic acid sodium salts (18) were synthesized and tested for their ability to inhibit HMG-CoA reductase in a partially purified enzyme preparation and cholesterol biosynthesis from acetate in cultured HEP-G2 cells. Changing the size of the saturated ring of the tetrahydroindazole nucleus did not improve potency, but incorporation of substituents at the 7-position resulted in up to 1700-fold improvement in inhibitory potency. Structure-activity studies revealed that the most potent compounds possess a substituted benzyl group at the 7-position, with a preference for steric bulk at the para position of the benzene ring. The most potent enzyme inhibitor (18t, IC50 = 3.0 nM) is approximately 3-fold more potent than lovastatin sodium salt (2). The most potent cholesterol biosynthesis inhibitor in HEP-G2 cells (18q, IC50 = 0.078 muM) is slightly less potent than 2 (sodium salt). Molecular modeling studies suggested that, when compared to the parent compound (18b) lacking the appropriate 7-substituent, 18t overlaps better with 2 and literature inhibitors 5 and 6 in a hydrophobic binding region adjacent to the enzyme active site.

  DOI：

  10.1021/jm00075a024

文献信息

• Tetrahydroindazole, tetrahydrocyclopentapyrazole, and
  申请人：Ortho Pharmaceutical Corporation

  公开号：US05134155A1

  公开（公告）日：1992-07-28

  Compounds of the general formula I: ##STR1## are disclosed as useful in the treatment or prevention of hypercholesterolemia, hyperlipoproteinemia and atherosclerosis. Novel intermediate compounds used to make the compound of formula I are also disclosed.

  通式I的化合物：##STR1## 被披露为在治疗或预防高胆固醇血症、高脂蛋白血症和动脉粥样硬化方面有用。还披露了用于制备通式I化合物的新型中间体化合物。
• Tetrahydroindazole, tetrahydrocyclopentapyrazole, and hexahydrocycloheptapyrazole compounds and their use as HMG-COA reductase inhibitors
  申请人：ORTHO PHARMACEUTICAL CORPORATION

  公开号：EP0529854A2

  公开（公告）日：1993-03-03

  Compounds of the general formula I : are disclosed as useful in the treatment or prevention of hypercholesterolemia, hyperlipoproteinemia and atherosclerosis. Novel intermediate compounds used to make the compound of formula I are also disclosed.

  通式 I 的化合物 ： 公开了用于治疗或预防高胆固醇血症、高脂蛋白血症和动脉粥样硬化的化合物。还公开了用于制造式 I 化合物的新型中间体化合物。
• US5134155A
  申请人：——

  公开号：US5134155A

  公开（公告）日：1992-07-28
• US5250561A
  申请人：——

  公开号：US5250561A

  公开（公告）日：1993-10-05
• US5315012A
  申请人：——

  公开号：US5315012A

  公开（公告）日：1994-05-24