1-((4-bromophenyl)carbamoyl)cyclopropane-1-carboxylic acid | 113136-80-4

• 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-((4-bromophenyl)carbamoyl)cyclopropane-1-carboxylic acid
• 英文别名: 1-[(4-Bromophenyl)carbamoyl]cyclopropane-1-carboxylic acid
• CAS: 113136-80-4
• 化学式: C₁₁H₁₀BrNO₃
• 分子量: 284.109
• InChiKey: QSNSWLRJDGFGMM-UHFFFAOYSA-N

物化性质

• 沸点：
  518.0±35.0 °C(Predicted)
• 密度：
  1.790±0.06 g/cm3(Predicted)

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-((4-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-(4-bromophenyl)-N'-(4-((5-fluoro-4-(4-fluoro-1-isopropyl-2-methyl-1H-benzo[d]imidazol-6-yl)pyrimidin-2-yl)amino)benzyl)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 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 1-((4-bromophenyl)carbamoyl)cyclopropane-1-carboxylic acid
  参考文献：
  名称：

  Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity

  摘要：

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.

  DOI：

  10.1021/ml500066m

文献信息

• [EN] NOVEL SMALL MOLECULE INHIBITORS OF TEAD TRANSCRIPTION FACTORS<br/>[FR] NOUVEAUX INHIBITEURS À PETITES MOLÉCULES DE FACTEURS DE TRANSCRIPTION TEAD
  申请人：MASSACHUSETTS GEN HOSPITAL

  公开号：WO2020190774A1

  公开（公告）日：2020-09-24

  The present disclosure compounds, as well as their compositions and methods of use. The compounds inhibit the activity of the TEAD transcription factor, and are useful in the treatment of diseases related to the activity of TEAD transcription factor including, e.g., cancer and other diseases.

  本公开涉及化合物及其组合物和使用方法。这些化合物抑制TEAD转录因子的活性，并可用于治疗与TEAD转录因子活性相关的疾病，例如癌症和其他疾病。
• PIDA-mediated N–N bond formation to access pyrazolidine-3,5-diones: a novel process for uricosuric agents G-25671 and sulfinpyrazone
  作者：Priyanka Halder、Santosh B. Mhaske

  DOI：10.1039/d3cc02078a

  日期：——

  building blocks are required to construct pharmaceutically important pyrazolidine-3,5-diones. Herein, we have described a novel method for their synthesis based on metal-free oxidative dehydrogenative N–N bond formation by PIDA-mediated reaction of easily accessible dianilide precursors. The developed mild reaction protocol features a good functional group tolerance and scalability. The application of

  传统上，需要有毒且昂贵的肼结构单元来构建药学上重要的吡唑烷-3,5-二酮。在此，我们描述了一种新的合成方法，该方法基于通过 PIDA 介导的易于获得的二苯胺前体的反应形成无金属氧化脱氢 N-N 键。所开发的温和反应方案具有良好的官能团耐受性和可扩展性。该方法的应用通过精心设计的面向多样性的环丙基关键中间体的顺利官能化，提供了一种从廉价的起始原料苯胺合成促尿酸排泄剂 G-25671 和磺吡酮的独特途径来证明。
• 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.
• Novel dual inhibitors targeting CDK4 and VEGFR2 synergistically suppressed cancer progression and angiogenesis
  作者：Zhi Huang、Borui Zhao、Zhongxiang Qin、Yongtao Li、Tianqi Wang、Wei Zhou、Jianyu Zheng、Shengyong Yang、Yi Shi、Yan Fan、Rong Xiang

  DOI：10.1016/j.ejmech.2019.07.044

  日期：2019.11

  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.
• Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity
  作者：Zhengsheng Zhan、Jing Ai、Qiufeng Liu、Yinchun Ji、Tiantian Chen、Yechun Xu、Meiyu Geng、Wenhu Duan

  DOI：10.1021/ml500066m

  日期：2014.6.12

  Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 mu M. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues.