2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl)methyl)piperazin-1-yl)-N-(4-(8-(hydroxyamino)-8-oxooctylamino)-3-nitrophenylsulfonyl)benzamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl)methyl)piperazin-1-yl)-N-(4-(8-(hydroxyamino)-8-oxooctylamino)-3-nitrophenylsulfonyl)benzamide
• 英文别名: 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-(4-((4'-chloro-5,5-dimethyl-3,4,5,6-tetrahydro-[1,1'-biphenyl]-2-yl)methyl)piperazin-1-yl)-N-((4-((8-(hydroxyamino)-8-oxooctyl)amino)-3-nitrophenyl)sulfonyl)benzamide；4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-N-[4-[[8-(hydroxyamino)-8-oxooctyl]amino]-3-nitrophenyl]sulfonyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide
• 化学式: C₄₇H₅₅ClN₈O₈S
• 分子量: 927.521
• InChiKey: XRVHYBBFEIGUQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  65
• 可旋转键数：
  18
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  223
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  8-氨基辛酸 在 4-二甲氨基吡啶 、 氯化亚砜 、 盐酸羟胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 39.03h， 生成 2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)-4-(4-((2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl)methyl)piperazin-1-yl)-N-(4-(8-(hydroxyamino)-8-oxooctylamino)-3-nitrophenylsulfonyl)benzamide
  参考文献：
  名称：

  Design, synthesis, and bioactivity evaluation of novel Bcl-2/HDAC dual-target inhibitors for the treatment of multiple myeloma

  摘要：

  Multiple myeloma (MM) is the second most common haematological malignancy. Almost all patients with MM eventually relapse, and most recommended treatment protocols for the patients with relapsed refractory MM comprise a combination of drugs with different mechanisms of action. Therefore novel drugs are in urgent need in clinic. Bcl-2 inhibitors and HDAC inhibitors were proved their anti-MM effect in clinic or under clinical trials, and they were further discovered to have synergistic interactions. In this study, a series of Bcl-2/HDAC dual-target inhibitors were designed and synthesized. Among them, compounds 7e-7g showed good inhibitory activities against HDAC6 and high binding affinities to Bcl-2 protein simultaneously. They also displayed good growth inhibitory activities against human MM cell line RPMI-8226, which proved their potential value for the treatment of multiple myeloma.

  DOI：

  10.1016/j.bmcl.2018.12.052

文献信息

• N-取代苯磺酰基-氮杂吲哚氧基苯甲酰胺类 化合物及其制备药物的用途
  申请人：中国人民解放军第二军医大学

  公开号：CN106957315B

  公开（公告）日：2019-08-13

  本发明涉及一类N‑取代苯磺酰基‑氮杂吲哚氧基苯甲酰胺类化合物，其晶型、药学上可接受的盐类、水合物、溶剂合物或前药，及其制备方法和制药用途。所述化合物的结构通式如式(Ⅰ)所示。试验表明其对Bcl‑2蛋白家族抗细胞凋亡成员和HDAC具有较高的抑制活性，并表现出结合选择性，同时该类化合物对人血液肿瘤(骨髓瘤、白血病)和实体瘤(卵巢癌、乳腺癌、黑色素瘤、肺癌)显示了广谱抗肿瘤活性。提示该类化合物具有制备与Bcl‑2或HDAC活性相关的疾病的治疗药物，制备抗肿瘤药物，以及制备增效剂与其它抗肿瘤药物或放射治疗合用以治疗肿瘤的潜在用途。