Ro-32-0432 | 131848-98-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Ro-32-0432
• 英文别名: bisindolylmaleimide XI；3-(8-((Dimethylamino)methyl)-6,7,8,9-tetrahydropyrido(1,2-a)indol-10-yl)-4-(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione；3-[8-[(dimethylamino)methyl]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl]-4-(1-methylindol-3-yl)pyrrole-2,5-dione
• CAS: 131848-98-1
• 化学式: C₂₈H₂₈N₄O₂
• 分子量: 452.556
• InChiKey: FXGHOAZJQNLNFD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  59.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  8-(acetoxymethyl)-6,7,8,9-tetrahydropyrido[1,2-a]indole 在 2,4,6-三甲基吡啶 、 ammonium hydroxide 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 79.0h， 生成 Ro-32-0432
  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

• Regulation of cardiac contractility and heart failure propensity
  申请人：Children's Hospital Medical Center

  公开号：EP1908827A2

  公开（公告）日：2008-04-09

  The methods and compositions of the present invention find use in altering expression of PKCα in transgenic animals. The compositions of the invention include isolated transgenic animal cells, transgenic tissue, transgenic animals, and transgenic mice. The transgenic animals of the invention exhibit altered PKCα activity. The methods allow generation of transgenic animals with altered expression of PKCα. The invention allows modulation of cardiac contractility. In particular, the invention provides a method for altering the susceptibility of a transgenic animal to cardiomyopathy. A transgenic animal of the invention finds use in identifying anti-cardiomyopathic compounds.

  本发明的方法和组合物可用于改变转基因动物中 PKCα 的表达。本发明的组合物包括分离的转基因动物细胞、转基因组织、转基因动物和转基因小鼠。本发明的转基因动物表现出改变的 PKCα 活性。本发明的方法可以产生 PKCα 表达改变的转基因动物。本发明可调节心脏收缩力。特别是，本发明提供了一种改变转基因动物对心肌病易感性的方法。本发明的转基因动物可用于鉴定抗心肌病化合物。
• Cancer treatment with compounds inhibiting PKC alpha
  申请人：Lu Zhimin

  公开号：US20060009492A1

  公开（公告）日：2006-01-12

  A chemotherapeutic cancer treatment with Gö7874, Gö6850, Gö7612, Gö7852, Ro31-7549, Ro31-8425, Ro31-8220, Ro31-0432 and NGIC-1 or chemical compounds with similar structures is administered to a mammal for the treatment of the cancer. The chemical compound is targeted to PKC α activity. Experiments indicate that Gö7874, Gö6850, Gö7612, Gö7852, Ro31-7549, Ro31-8425, Ro31-8220, Ro31-0432 and NGIC-1 and similar compounds to be effective for the treatment of breast cancer, leukemia, lung cancer, skin cancer, prostate cancer, liver cancer, brain tumor, cervical cancer, and cancers located in the digestive tract including gastric cancer and colorectal cancers. These treatments may be accomplished utilizing Gö7874, Gö6850, Gö7612, Gö7852, Ro31-7549, Ro31-8425, Ro31-8220, Ro31-0432 and NGIC-1 and chemical compounds with similar structures alone or in combination with prior art chemotherapy agents or with radiation therapy. In a preferred embodiment Gö7874, Gö6850, Gö7612, Gö7852, Ro31-7549, Ro31-8425, Ro31-8220, Ro31-0432 and NGIC-1 chemical compounds with similar structures is used for the treatment of cancer as a preventative drug by preventing cancer cell formation.

  向哺乳动物施用 Gö7874、Gö6850、Gö7612、Gö7852、Ro31-7549、Ro31-8425、Ro31-8220、Ro31-0432 和 NGIC-1 或具有类似结构的化合物进行癌症化疗，以治疗癌症。该化合物针对 PKC α 的活性。实验表明，Gö7874、Gö6850、Gö7612、Gö7852、Ro31-7549、Ro31-8425、Ro31-8220、Ro31-0432 和 NGIC-1 及类似化合物可有效治疗乳腺癌、白血病、肺癌、皮肤癌、前列腺癌、肝癌、脑瘤、宫颈癌和消化道癌症，包括胃癌和结肠直肠癌。这些治疗可以利用 Gö7874、Gö6850、Gö7612、Gö7852、Ro31-7549、Ro31-8425、Ro31-8220、Ro31-0432 和 NGIC-1 以及具有类似结构的化合物，单独使用或与现有技术的化疗药物或放射治疗联合使用。在一个优选的实施方案中，Gö7874、Gö6850、Gö7612、Gö7852、Ro31-7549、Ro31-8425、Ro31-8220、Ro31-0432 和具有类似结构的 NGIC-1 化合物通过阻止癌细胞的形成，作为预防药物用于癌症的治疗。
• Substituierte Pyrrole
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP0384349B1

  公开（公告）日：1994-04-27
• THREE-DIMENSIONAL STRUCTURE OF THE CATALYTIC DOMAIN OF PROTEIN C THETA, METHODS AND USE THEREOF
  申请人：Novartis AG

  公开号：EP1599583A1

  公开（公告）日：2005-11-30
• Three-dimensional structure of the catalytic domain of protein kinase c theta, methods and uses thereof
  申请人：Rummel Gabriele

  公开号：US20070072281A1

  公开（公告）日：2007-03-29

  The present invention concerns protein kinase C (PKC) theta, in particular, the three-dimensional structure of the catalytic domain of PKC theta. Methods of expression, purification and crystallization of PKC theta catalytic domain are provided in preparation for crystallography. The atomic coordinates of a complex of PKC theta complexed with an inhibitor are also provided.