Pravachol

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: Pravachol
• 英文别名: (3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoate
• 化学式: C23H35O7-
• 分子量: 423.5
• InChiKey: TUZYXOIXSAXUGO-PZAWKZKUSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.74
• 拓扑面积：
  127
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  sodium methylate 、 Pravachol 、 普伐他汀 在 甲醇 、 正己烷 作用下， 以 甲醇 为溶剂， 反应 60.0h， 以to give 120 g of the title compound的产率得到sodium (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8AR)-6,8-dihydroxy-2-methyl-1,2,6,7,8,8a-hexahydro-1-naphthyl]heptanoate
  参考文献：
  名称：

  Hexahydronaphthalene ester derivatives their preparation and their

  摘要：

  化合物的式子（I）：##STR1## 其中R.sup.1代表式子（II）或（III）的基团：##STR2## R.sup.2是烷基，烯基或炔基；R.sup.3和R.sup.4分别是氢，烷基，烯基或炔基；R.sup.5是氢或羧基保护基团；R.sup.a是式子--OR.sup.6的基团；R.sup.6是氢；R.sup.6a和R.sup.6b分别是氢，羟基保护基团，烷基，烷基磺酰，卤代烷基磺酰或芳基磺酰，以及它们的盐和酯。这些化合物抑制胆固醇的合成，可用于治疗和预防高胆固醇血症和各种心脏疾病。

  公开号：

  US05827855A1
• 作为产物：
  描述：

  水 、 普伐他汀类酯 生成 氢(+1)阳离子 、 Pravachol
  参考文献：
  名称：

  摘要：

  The pH dependence of the interconversion kinetics, equilibrium, and solubilities of the lactone and hydroxyacid forms of the HMG-CoA reductase inhibitor, CI-981 ([R-(R*,R*)]-2-(4-fluorophenyl)-beta,delta-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylamino)carbonyl]-1H-pyrrole-1-hepatonic acid), are important considerations when chosing and developing one of the forms of these compounds. Over a pH range of 2.1 to 6.0 and at 30-degrees-C, the apparent solubility of the sodium salt of CI-981 (i.e., the hydroxyacid form) increases about 60-fold, from 20.4 mug/mL to 1.23 mg/mL, and the profile yields a pK(a) for the terminal carboxyl group of 4.46. In contrast, over a pH range of 2.3 to 7.7 and also at 30-degrees-C, the apparent solubility of the lactone form of CI-981 varies little, and the mean solubility is 1.34 (+/-0.53) mug/mL. The kinetics of interconversion and the equilibrium between the hydroxyacid and the lactone forms have been studied as a function of pH, buffer concentration, and temperature at a fixed ionic strength (0.5 M) using a stability-indicating HPLC assay. The acid-catalyzed reaction is reversible, whereas the base-catalyzed reaction can be treated as an irreversible reaction. More specifically, at pH <6, an equilibrium favoring the hydroxyacid form is established, whereas at pH >6, the equilibrium reaction is no longer detectable and greatly favors the hydroxyacid form. The rate constant for lactone formation, k1, is well described by specific acid-catalyzed and spontaneous lactonization pathways, whereas the rate constant for lactone hydrolysis (or hydroxyacid formation), k2, is well described by specific acid-, water-, and specific base-catalyzed pathways.

  DOI：

  10.1023/a:1018923325359