1-((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)cyclopropanecarboxylic acid | 1455870-60-6

• 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-chloro-3-(trifluoromethyl)phenyl)carbamoyl)cyclopropanecarboxylic acid
• 英文别名: 1-((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)cyclopropane-1-carboxylic acid；1-[[4-Chloro-3-(trifluoromethyl)phenyl]carbamoyl]cyclopropane-1-carboxylic acid
• CAS: 1455870-60-6
• 化学式: C₁₂H₉ClF₃NO₃
• 分子量: 307.657
• InChiKey: WNCNOLJSULIGDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)cyclopropanecarboxylic 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-chloro-3-(trifluoromethyl)phenyl)-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 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 生成 1-((4-chloro-3-(trifluoromethyl)phenyl)carbamoyl)cyclopropanecarboxylic 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

• 取代的吡啶-2-甲酰胺类化合物及其用途
  申请人：北京福元医药股份有限公司

  公开号：CN111362871B

  公开（公告）日：2022-05-17

  本发明属于药物化学技术领域，涉及取代的吡啶‑2‑甲酰胺类化合物及其用途。具体而言，该取代的吡啶‑2‑甲酰胺类化合物具有式I结构。针对VEGFR‑2，PDGFR‑β两种激酶的优异的体外抑制活性和HUVEC细胞抑制活性，使其可以作为小分子的酪氨酸激酶(特别是Raf激酶)抑制剂，具有抑制细胞增殖及血管生成的作用，具有良好的抗肿瘤活性，对于治疗哺乳动物(包括人类)的肿瘤性疾病具有良好的效果。
• 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.