(3S,8S,9S,10R)-6-dodecanoyloxyl-3-hydroxymethyl-8-isopropyl-8-methyl-3,3a,8,8a-tetrahydro-2H-2-aza-cyclopenta[a]inden-1-one | 348642-95-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 英文名称: (3S,8S,9S,10R)-6-dodecanoyloxyl-3-hydroxymethyl-8-isopropyl-8-methyl-3,3a,8,8a-tetrahydro-2H-2-aza-cyclopenta[a]inden-1-one
• 英文别名: [(1S,3aS,4S,8bR)-1-(hydroxymethyl)-4-methyl-3-oxo-4-propan-2-yl-1,2,3a,8b-tetrahydroindeno[1,2-c]pyrrol-6-yl] dodecanoate
• CAS: 348642-95-5
• 化学式: C₂₈H₄₃NO₄
• 分子量: 457.654
• InChiKey: PXONMVAMARNSJO-GTVIQNQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  33
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S,8S,9S,10R)-6-dodecanoyloxyl-3-hydroxymethyl-8-isopropyl-8-methyl-3,3a,8,8a-tetrahydro-2H-2-aza-cyclopenta[a]inden-1-one 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 乙腈 为溶剂， 反应 1.0h， 生成 (3S,8S,9S,10R)-5,7-dibromo-6-dodecanoyloxyl-3-hydroxymethyl-8-isopropyl-8-methyl-3,3a,8,8a-tetrahydro-2H-2-aza-cyclopenta[a]inden-1-one
  参考文献：
  名称：

  Rigid pyrrolidone modulators of pkc

  摘要：

  通式（I）的化合物：其中R1、R2、R3和R4的取代基具有规范中定义的任何值，以及它们的药学上可接受的盐，是PKC调节剂，可用于治疗疾病，例如癌症（包括前列腺癌）、炎症、自身免疫和神经系统疾病（包括阿尔茨海默病）。还公开了包括通式（I）化合物的制药组合物、制备通式（I）化合物的方法，以及制备通式（I）化合物有用的中间体。

  公开号：

  US20040019018A1
• 作为产物：
  描述：

  2-溴-5-羟基苯甲醛 在 palladium on activated charcoal 吡啶 、 六甲基磷酰三胺 、 4-二甲氨基吡啶 、 偶氮二异丁腈 、 三氟化硼乙醚 、 氢氟酸 、 氢气 、 三正丁基氢锡 、 sodium hydride 、 magnesium 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 生成 (3S,8S,9S,10R)-6-dodecanoyloxyl-3-hydroxymethyl-8-isopropyl-8-methyl-3,3a,8,8a-tetrahydro-2H-2-aza-cyclopenta[a]inden-1-one
  参考文献：
  名称：

  Rational design, synthesis, and biological evaluation of rigid pyrrolidone analogues as potential inhibitors of prostate cancer cell growth

  摘要：

  In view of its role in tumor promotion and signal transduction, protein kinase C (PKC) has proven to be an exciting target for cancer therapy. With the aid of molecular modeling, we rationally designed and stereoselectively synthesized a new class of rigidified pyrrolidone-based PKC activators. Pyrrolidone 15 was found to exhibit reasonable affinity for PKC delta, with lower affinity for the other isozymes tested. Pyrrolidone 2 causes the dose-dependent induction of apoptosis in LNCaP prostate cancer cells. This apoptotic effect could be markedly potentiated by the use of LNCaP cells overexpressing the PKC alpha or delta isozymes. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00097-x

文献信息

• Rational design, synthesis, and biological evaluation of rigid pyrrolidone analogues as potential inhibitors of prostate cancer cell growth
  作者：Lixin Qiao、Lian-Yun Zhao、Suo-Bao Rong、Xiong-Wu Wu、Shaomeng Wang、Teruhiko Fujii、Marcelo G Kazanietz、Laura Rauser、Jason Savage、Bryan L Roth、Judith Flippen-Anderson、Alan P Kozikowski

  DOI：10.1016/s0960-894x(01)00097-x

  日期：2001.4

  In view of its role in tumor promotion and signal transduction, protein kinase C (PKC) has proven to be an exciting target for cancer therapy. With the aid of molecular modeling, we rationally designed and stereoselectively synthesized a new class of rigidified pyrrolidone-based PKC activators. Pyrrolidone 15 was found to exhibit reasonable affinity for PKC delta, with lower affinity for the other isozymes tested. Pyrrolidone 2 causes the dose-dependent induction of apoptosis in LNCaP prostate cancer cells. This apoptotic effect could be markedly potentiated by the use of LNCaP cells overexpressing the PKC alpha or delta isozymes. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Rigid pyrrolidone modulators of pkc
  申请人：——

  公开号：US20040019018A1

  公开（公告）日：2004-01-29

  Compounds of the general formula (I): wherein substituents at R 1 , R 2 , R 3 and R 4 have any of the values defined in the specification, and their pharmaceutically acceptable salts, are PKC modulators and are useful for treating diseases, such as, for example, cancers including prostate cancer, inflammatory, autoimmune and neurological disorders including Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising compounds of formula (I), processes for preparing compounds of formula (I), and intermediates useful for preparing compounds of formula (I).

  通式（I）的化合物：其中R1、R2、R3和R4的取代基具有规范中定义的任何值，以及它们的药学上可接受的盐，是PKC调节剂，可用于治疗疾病，例如癌症（包括前列腺癌）、炎症、自身免疫和神经系统疾病（包括阿尔茨海默病）。还公开了包括通式（I）化合物的制药组合物、制备通式（I）化合物的方法，以及制备通式（I）化合物有用的中间体。