(1S,2S,3S,5R)-isopinocampheyl 2-(3-pyridyl)propanoate

• 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,2S,3S,5R)-isopinocampheyl 2-(3-pyridyl)propanoate
• 英文别名: [(1S,2S,3S,5R)-2,6,6-trimethyl-3-bicyclo[3.1.1]heptanyl] 2-pyridin-3-ylpropanoate
• 化学式: C₁₈H₂₅NO₂
• 分子量: 287.402
• InChiKey: LTFXSOGYCIGJBD-HFOAVAATSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.67
• 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：

  (1S,2S,3S,5R)-(+)-异松蒎醇 在 正丁基锂 、 potassium hydride 作用下， 反应 5.25h， 生成 (1S,2S,3S,5R)-isopinocampheyl 2-(3-pyridyl)propanoate
  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

• HETEROCYCLIC COMPOUNDS, THEIR PREPARATION AND PHARMACEUTICAL USE
  申请人：BRITISH TECHNOLOGY GROUP LTD

  公开号：EP0594629A1

  公开（公告）日：1994-05-04
• [EN] HETEROCYCLIC COMPOUNDS, THEIR PREPARATION AND PHARMACEUTICAL USE
  申请人：BRITISH TECHNOLOGY GROUP LIMITED

  公开号：WO1992016507A1

  公开（公告）日：1992-10-01

  (EN) Compounds having the general formula (3), wherein each of R1 and R2 independently represents hydrogen or C1-4 alkyl or together represent the residue of a cycloalkyl group of 3 to 6 carbon atoms; A represents O, NR4 wherein R4 is defined as for R1 or R2 or CR5R6 wherein R5 and R6 are as defined for R1 or R2 as separate substituents; and R3 represents a bridged alicyclic group; as free bases or their pharmaceutically acceptable salts are useful in treating androgen-dependent, especially prostatic, cancer.(FR) On décrit des composés de formule générale (3), dans laquelle R1 et R2 représentent indépendamment hydrogène ou C1-4¿ alkyle ou ensemble représentent le reste d'un groupe cycloalkyle de 3 à 6 atomes de carbone; A représente O, NR4 où R4 a la même définition que R1 ou R2 ou CR5R6, où R5 et R6 ont la même définition que R1 ou R2 en tant que substituants séparés; et R3¿ représente un groupe alicyclic ponté; comme bases libres ou leurs sels pharmaceutiquement acceptables. Lesdits composés sont utiles pour traiter les cancers liés à l'androgène et surtout celui du prostate.
• 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.