1-((3-bromophenyl)carbamoyl)cyclopropane-1-carboxylic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-((3-bromophenyl)carbamoyl)cyclopropane-1-carboxylic acid
• 英文别名: 1-[(3-Bromophenyl)carbamoyl]cyclopropane-1-carboxylic acid
• 化学式: C₁₁H₁₀BrNO₃
• 分子量: 284.109
• InChiKey: JTJZJZFIKXNWIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-((3-bromophenyl)carbamoyl)cyclopropane-1-carboxylic acid 在 palladium diacetate 、 1-羟基苯并三唑 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 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 作用下， 以 N,N-二甲基甲酰胺 、 1,4-二甲基环己烷 为溶剂， 反应 24.0h， 生成 N-(3-bromophenyl)-N'-(4-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)phenyl)cyclopropane-1,1-dicarboxamide
  参考文献：
  名称：

  Novel dual inhibitors targeting CDK4 and VEGFR2 synergistically suppressed cancer progression and angiogenesis

  摘要：

  Based on the significantly synergistic effects of CDK4 and VEGFR2 inhibitors on growth of cancer cells, a series of novel multi-kinase inhibitors targeting CDK4 and VEGFR2 were designed, synthesized and evaluated, among which Roxyl-ZV-5J exhibited potent and balanced activities against both CDK4 and VEGFR2 with half-maximal inhibitory concentration at the nanomolar level. It effectively induced breast and cervical cancer cell cycle arrest and cell apoptosis. Roxyl-ZV-5J also inhibited the proliferation, tube formation and VEGFR2 downstream signaling pathways of HUVECs. Oral administration of Roxyl-ZV-5J led to significant tumor regression and anti-angiogenesis without obvious toxicity in SiHa xenograft mouse model. In addition, this compound showed good pharmacokinetics. This study confirmed a new tool for dual CDK-VEGFR2 pathways inhibition achieved with a single molecule, which provided valuable leads for further structural optimization and anti-angiogenesis and anti-tumor mechanism study. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.044
• 作为产物：
  描述：

  1,1-环丙基二羧酸 、 间溴苯胺 在 氯化亚砜 、 三乙胺 作用下， 以 醋酸异丙酯 为溶剂， 反应 8.0h， 以76%的产率得到1-((3-bromophenyl)carbamoyl)cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  Novel dual inhibitors targeting CDK4 and VEGFR2 synergistically suppressed cancer progression and angiogenesis

  摘要：

  Based on the significantly synergistic effects of CDK4 and VEGFR2 inhibitors on growth of cancer cells, a series of novel multi-kinase inhibitors targeting CDK4 and VEGFR2 were designed, synthesized and evaluated, among which Roxyl-ZV-5J exhibited potent and balanced activities against both CDK4 and VEGFR2 with half-maximal inhibitory concentration at the nanomolar level. It effectively induced breast and cervical cancer cell cycle arrest and cell apoptosis. Roxyl-ZV-5J also inhibited the proliferation, tube formation and VEGFR2 downstream signaling pathways of HUVECs. Oral administration of Roxyl-ZV-5J led to significant tumor regression and anti-angiogenesis without obvious toxicity in SiHa xenograft mouse model. In addition, this compound showed good pharmacokinetics. This study confirmed a new tool for dual CDK-VEGFR2 pathways inhibition achieved with a single molecule, which provided valuable leads for further structural optimization and anti-angiogenesis and anti-tumor mechanism study. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.07.044

文献信息

• 新型1,1-环丙基二酰胺衍生物的制备与应用
  申请人：南开大学

  公开号：CN108929324A

  公开（公告）日：2018-12-04

  本发明新型1,1‑环丙基二酰胺衍生物的制备与应用，涉及新的具有式(I)的1,1‑环丙基二酰胺衍生物及其盐、包括可药用盐，其中R1、R2、R3、R4、R5和X、Z、L在本文被定义。包括可药用盐。本发明的化合物可用于治疗HIV及癌症类疾病，包括肺癌，肝癌，乳腺癌，淋巴癌，套细胞淋巴瘤、脂肉瘤、黑素瘤、鳞状细胞食管癌等。本发明的药物组合物能够制成有利于哺乳动物的组织、器官吸收利用的剂型，其在治疗癌症和HIV等疾病具有良好的应用前景。本发明还涉及包含本发明的化合物的药物组合物。
• Discovery of a highly potent, selective and novel CDK9 inhibitor as an anticancer drug candidate
  作者：Yongtao Li、Qingxiang Guo、Chao Zhang、Zhi Huang、Tianqi Wang、Xin Wang、Xiang Wang、Guangwei Xu、Yanhua Liu、Shengyong Yang、Yan Fan、Rong Xiang

  DOI：10.1016/j.bmcl.2017.06.041

  日期：2017.8

  A series of novel hybrid structure derivatives, containing both LEE011 and Cabozantinib pharmacophore, were designed, synthesized and evaluated. Surprisingly, a compound 4d was discovered that highly exhibited effective and selective activity of CDK9 inhibition with IC50 = 12 nM. It effectively induced apoptosis in breast and lung cancer cell lines at nanomolar level. Molecular docking of 4d to ATP binding site of CDK9 kinase demonstrated a new hydrogen bonding between F atom of 4-(3-fluorobenzyloxy) group and ASN116 residue, compared with the positive control, LEE011. The compound 4d could block the cell cycle both in G0/G1 and G2/M phase to prevent the proliferation and differentiation of cancer cells. Mice bared-breast cancer treated with compound 4d showed significant suppression of cancer with low toxicity. Taken together, this novel compound 4d could be a promising drug candidate for clinical application. (C) 2017 Elsevier Ltd. All rights reserved.