[(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-piperidin-1-ylethyl)carbamate | 118046-33-6

• 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: [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-piperidin-1-ylethyl)carbamate
• CAS: 118046-33-6
• 化学式: C₂₈H₄₆N₂O₇
• 分子量: 522.682
• InChiKey: SKSXASSXTOSPTG-FCTGTBMNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  129
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-(2-氨乙基)哌啶 在 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 20.0h， 生成 [(3R,4aR,5S,6S,6aS,10S,10aR,10bS)-3-ethenyl-6,10,10b-trihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-5,6,6a,8,9,10-hexahydro-2H-benzo[f]chromen-5-yl] N-(2-piperidin-1-ylethyl)carbamate
  参考文献：
  名称：

  Forskolin Carbamates: Binding and Activation Studies with Type I Adenylyl Cyclase

  摘要：

  Three series of analogs were regioselectively prepared from a protected forskolin precursor to afford 7-carbamoyl-7-desacetylforskolins (series 1), 6-carbamoyl-7-desacetylforskolins (series 2), and 6-carbamoylforskolins (series 3). The analogs were pharmacologically evaluated for binding (IC50) to and activation (EC(50)) of type I adenylyl cyclase in membranes from stably transfected Sig cell lines expressing a single adenylate cyclase subtype. The following ranges were determined for the IC50's and EC(50)'s of each individual series: series 1, IC50 = 43-1600 nM, EC(50) = 0.5-9.6 mu M; series 2, IC50 = 65-680 nM, EC(50) = 0.63-6.5 mu M; series 3, IC50 = 21-271 nM, EC(50) = 0.5-8.1 mu M (forskolin IC50 = 41 nM and EC(50) = 0.5 mu M). Activation paralleled binding; however, some analogs exhibited poor binding and good activation whereas others demonstrated good binding but poor activation. Steric bulk tended to diminish binding and activation when at the 6- or 7-position, although bulk was accommodated at the 6-position if the 7-site was reacetylated. Acylation of the 7-position by the carbamoyl linker or acetyl was important for obtaining good binding and activation; however, the effect was more pronounced with binding. For both binding and activation, small, linear, lipophilic substituents (propyl, allyl, isopropyl) are well tolerated at the 7-position but less so in the 6-position, even when the 7-site is reacetylated. Planar aromatic moieties (phenyl and 2-pyridinyl) demonstrated moderate to good potency for binding and activation when located at either the 6- or 7-positions. There is an overall trend toward increasing potency for both binding and activation with polar substituents.

  DOI：

  10.1021/jm960191+

文献信息

• Forskolin Carbamates: Binding and Activation Studies with Type I Adenylyl Cyclase
  作者：Joan D. Robbins、Daniel L. Boring、Wei-Jen Tang、Robin Shank、Kenneth B. Seamon

  DOI：10.1021/jm960191+

  日期：1996.1.1

  Three series of analogs were regioselectively prepared from a protected forskolin precursor to afford 7-carbamoyl-7-desacetylforskolins (series 1), 6-carbamoyl-7-desacetylforskolins (series 2), and 6-carbamoylforskolins (series 3). The analogs were pharmacologically evaluated for binding (IC50) to and activation (EC(50)) of type I adenylyl cyclase in membranes from stably transfected Sig cell lines expressing a single adenylate cyclase subtype. The following ranges were determined for the IC50's and EC(50)'s of each individual series: series 1, IC50 = 43-1600 nM, EC(50) = 0.5-9.6 mu M; series 2, IC50 = 65-680 nM, EC(50) = 0.63-6.5 mu M; series 3, IC50 = 21-271 nM, EC(50) = 0.5-8.1 mu M (forskolin IC50 = 41 nM and EC(50) = 0.5 mu M). Activation paralleled binding; however, some analogs exhibited poor binding and good activation whereas others demonstrated good binding but poor activation. Steric bulk tended to diminish binding and activation when at the 6- or 7-position, although bulk was accommodated at the 6-position if the 7-site was reacetylated. Acylation of the 7-position by the carbamoyl linker or acetyl was important for obtaining good binding and activation; however, the effect was more pronounced with binding. For both binding and activation, small, linear, lipophilic substituents (propyl, allyl, isopropyl) are well tolerated at the 7-position but less so in the 6-position, even when the 7-site is reacetylated. Planar aromatic moieties (phenyl and 2-pyridinyl) demonstrated moderate to good potency for binding and activation when located at either the 6- or 7-positions. There is an overall trend toward increasing potency for both binding and activation with polar substituents.