(1S,2R,3S,5R)-isopinocampheyl 2-pyridylacetate

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1S,2R,3S,5R)-isopinocampheyl 2-pyridylacetate
• 英文别名: [(1S,2S,3S,5R)-2,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl] 2-pyridin-2-ylacetate
• 化学式: C₁₇H₂₃NO₂
• 分子量: 273.375
• InChiKey: YDAMVJCAROVWAP-NEBZKDRISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-吡啶乙酸甲酯 、 (1S,2S,3S,5R)-(+)-异松蒎醇 在 正丁基锂 作用下， 生成 (1S,2R,3S,5R)-isopinocampheyl 2-pyridylacetate
  参考文献：
  名称：

  Esters of 3-Pyridylacetic Acid That Combine Potent Inhibition of 17.alpha.-Hydroxylase/C17,20-Lyase (Cytochrome P45017.alpha.) with Resistance to Esterase Hydrolysis

  摘要：

  Esters of 3- and 4-pyridylacetic acid have been prepared and tested for inhibitory activity toward the human testicular 17 alpha-hydroxylase/C-17,C-20-lyase and human placental aromatase enzymes. The structural features required for optimal inhibition of the hydroxylase/lyase enzyme were a 3-pyridine ring, methyl substitution alpha to the carbonyl group, and a bulky alkoxycarbonyl substituent. The compounds with the greatest selectivity were isopinpcampheyl 2-methyl-2-(3-pyridyl)propanoate, 9, 1-adamantyl 2-methyl-2-(3-pyridyl)propanoate, 12, and 2-methyl-2-adamantyl 2-methyl-2-(3-pyridyl)propanoate, 14, which, while inhibiting the aromatase activity with IC50 values of 30, 35, and 40 mu M, respectively, exhibited IC50 values toward hydroxylase/lyase of between 13 and 90 nM. For comparison, ketoconazole gave an IC50 value of 15 mu M against aromatase and values of 65 and 26 nM for inhibition of the hydroxylase and lyase activities, respectively. Some of the structural features required for enzyme inhibition also conferred resistance to esterase hydrolysis, in vitro using rat liver microsomes as a source of the esterase activity. Therefore these esters are lead compounds in the development of inhibitors of androgen biosynthesis for the treatment of hormone-dependent prostatic cancer.

  DOI：

  10.1021/jm00021a008

文献信息

• Esters of 3-Pyridylacetic Acid That Combine Potent Inhibition of 17.alpha.-Hydroxylase/C17,20-Lyase (Cytochrome P45017.alpha.) with Resistance to Esterase Hydrolysis
  作者：Martin G. Rowlands、S. Elaine Barrie、Ferdinand Chan、John Houghton、Michael Jarman、Raymond McCague、Gerard A. Potter

  DOI：10.1021/jm00021a008

  日期：1995.10

  Esters of 3- and 4-pyridylacetic acid have been prepared and tested for inhibitory activity toward the human testicular 17 alpha-hydroxylase/C-17,C-20-lyase and human placental aromatase enzymes. The structural features required for optimal inhibition of the hydroxylase/lyase enzyme were a 3-pyridine ring, methyl substitution alpha to the carbonyl group, and a bulky alkoxycarbonyl substituent. The compounds with the greatest selectivity were isopinpcampheyl 2-methyl-2-(3-pyridyl)propanoate, 9, 1-adamantyl 2-methyl-2-(3-pyridyl)propanoate, 12, and 2-methyl-2-adamantyl 2-methyl-2-(3-pyridyl)propanoate, 14, which, while inhibiting the aromatase activity with IC50 values of 30, 35, and 40 mu M, respectively, exhibited IC50 values toward hydroxylase/lyase of between 13 and 90 nM. For comparison, ketoconazole gave an IC50 value of 15 mu M against aromatase and values of 65 and 26 nM for inhibition of the hydroxylase and lyase activities, respectively. Some of the structural features required for enzyme inhibition also conferred resistance to esterase hydrolysis, in vitro using rat liver microsomes as a source of the esterase activity. Therefore these esters are lead compounds in the development of inhibitors of androgen biosynthesis for the treatment of hormone-dependent prostatic cancer.