6,7,8,9-tetrahydropyrido<1,2-a>indole-8(S)-carboxylic acid l-menthyl ester | 145317-24-4

• 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: 6,7,8,9-tetrahydropyrido<1,2-a>indole-8(S)-carboxylic acid l-menthyl ester
• 英文别名: 6,7,8,9-tetrahydropyrido[1,2-a]indole-8(S)-carboxylic acid l-menthyl ester；[(1R,2S,5R)-5-methyl-2-propan-2-ylcyclohexyl] (8S)-6,7,8,9-tetrahydropyrido[1,2-a]indole-8-carboxylate
• CAS: 145317-24-4
• 化学式: C₂₃H₃₁NO₂
• 分子量: 353.505
• InChiKey: ICEPFSOYIZUEJV-DCZASFAJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6,7,8,9-tetrahydropyrido<1,2-a>indole-8(S)-carboxylic acid l-menthyl ester 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 17.17h， 生成 8(S)-(acetoxymethyl)-6,7,8,9-tetrahydropyrido<1,2-a>indole
  参考文献：
  名称：

  Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction

  摘要：

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.

  DOI：

  10.1021/jm00053a003
• 作为产物：
  描述：

  L-薄荷醇 、 6,7,8,9-tetrahydropyrido<1,2-a>indole-8-carboxylic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 6,7,8,9-tetrahydropyrido<1,2-a>indole-8(R)-carboxylic acid l-menthyl ester 、 6,7,8,9-tetrahydropyrido<1,2-a>indole-8(S)-carboxylic acid l-menthyl ester
  参考文献：
  名称：

  Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction

  摘要：

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.

  DOI：

  10.1021/jm00053a003

文献信息

• Inhibitors of protein kinase C. 3. Potent and highly selective bisindolylmaleimides by conformational restriction
  作者：Rino A. Bit、Peter D. Davis、Lucy H. Elliott、William Harris、Christopher H. Hill、Elizabeth Keech、Hari Kumar、Geoffrey Lawton、Anna Maw、John S. Nixon、David R. Vesey、Julie Wadsworth、Sandra E. Wilkinson

  DOI：10.1021/jm00053a003

  日期：1993.1

  The protein kinase inhibitor staurosporine has been used to design a series of selective bisindolylmaleimide inhibitors of protein kinase C (PKC). Guided by molecular graphics, conformational restriction of the cationic side chain has led to ATP competitive inhibitors of improved potency and selectivity. Two compounds have been further evaluated and were shown to inhibit PKC of human origin and prevent T-cell activation in a human allogeneic mixed lymphocyte reaction. One of these compounds was orally absorbed in mice and antagonized a phorbol ester induced paw edema in a dose-dependent manner. This compound also selectively inhibited the secondary T-cell mediated response in a developing adjuvant arthritis model in rats and provides evidence for the potential use of PKC inhibitors as therapeutic immunomodulators.