phenyl (4-(diethylamino)phenyl)carbamate | 20950-94-1

• 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: phenyl (4-(diethylamino)phenyl)carbamate
• 英文别名: N-(4-Diethylamino-phenyl)-carbaminsaeure-phenylester；phenyl N-[4-(diethylamino)phenyl]carbamate
• CAS: 20950-94-1
• 化学式: C₁₇H₂₀N₂O₂
• 分子量: 284.358
• InChiKey: GLFRMBWMSFYJLA-UHFFFAOYSA-N

物化性质

• 沸点：
  406.3±37.0 °C(Predicted)
• 密度：
  1.158±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  phenyl (4-(diethylamino)phenyl)carbamate 、 4-(3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)aniline 在 1-甲基吡咯烷 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 生成 N-((4-diethylamino)phenyl)-N'-(4-(3-methyl-1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl)urea
  参考文献：
  名称：

  Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

  DOI：

  10.1021/acs.jmedchem.7b00468
• 作为产物：
  描述：

  N,N-二乙基-4-硝基苯胺 在 吡啶 、 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 生成 phenyl (4-(diethylamino)phenyl)carbamate
  参考文献：
  名称：

  Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)

  摘要：

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.

  DOI：

  10.1021/acs.jmedchem.7b00468

文献信息

• Discovery of a Novel CSF-1R Inhibitor with Highly Improved Pharmacokinetic Profiles and Superior Efficacy in Colorectal Cancer Immunotherapy
  作者：Qi Lv、Hongqiong Yang、Dan Wang、Haikun Zhou、Juan Wang、Yishu Zhang、Dapeng Wu、Ying Xie、Yingshan Lv、Lihong Hu、Junwei Wang

  DOI：10.1021/acs.jmedchem.4c00508

  日期：2024.4.25

  CSF-1/CSF-1R pathway has emerged as a promising strategy to remodel tumor immune microenvironment (TME) by reprogramming tumor-associated macrophages (TAMs). In this work, a novel CSF-1R inhibitor C19 with a highly improved pharmacokinetic profile and in vivo anticolorectal cancer (CRC) efficiency was successfully discovered. C19 could effectively reprogram M2-like TAMs to M1 phenotype and reshape the TME

  阻断 CSF-1/CSF-1R 通路已成为通过重新编程肿瘤相关巨噬细胞 (TAM) 来重塑肿瘤免疫微环境 (TME) 的有前途的策略。在这项工作中，成功发现了一种新型 CSF-1R 抑制剂C19 ，其具有显着改善的药代动力学特征和体内抗结直肠癌 (CRC) 功效。 C19可以有效地将 M2 样 TAM 重编程为 M1 表型，并通过诱导 CD8 + T 细胞招募到肿瘤中并减少免疫抑制性 Tregs/MDSC 的浸润来重塑 TME。更深入的机制研究表明， C19通过增强趋化因子 CXCL9 的分泌来促进 CD8 + T 细胞的浸润，从而显着增强 PD-1 阻断的抗 CRC 效率。更重要的是， C19联合PD-1 mAb可以诱导持久的抗肿瘤免疫记忆，有效克服CRC的复发。综上所述，我们的研究结果表明， C19是一种有前途的治疗选择，可以提高 CRC 对抗 PD-1 疗法的敏感性。
• Discovery of 4-piperazinyl-2-aminopyrimidine derivatives as dual inhibitors of JAK2 and FLT3
  作者：Yingxiu Li、Tianyu Ye、Le Xu、Yuhong Dong、Yong Luo、Chu Wang、Yufei Han、Ke Chen、Mingze Qin、Yajing Liu、Yanfang Zhao

  DOI：10.1016/j.ejmech.2019.111590

  日期：2019.11

  Hybridization strategy is an effective strategy to obtain multi-target inhibitors in drug design. In this study, we assembled the pharmacophores of momelotinib and tandutinib to get a series of 4-piperazinyl-2-aminopyrimidine derivatives. All compounds were tested for the inhibition of JAK2 and FLT3 enzymes, of which, compounds with potent enzyme activities were assayed for antiproliferative activities against three cancer cell lines (HEL, MV4-11, and HL60). The structure-activity relationship studies were conducted through variations in two regions, the "A" phenyl ring and "B" phenyl ring. Compound 14j showed the most balanced in vitro inhibitory activity against JAK2 and FLT3 (JAK2 IC50 = 27 nM, FLT3 IC50 = 30 nM), and it also showed potent inhibition against the above tested cell lines. In the cellular context, 14j strongly induced apoptosis by arresting cell cycle in the G(1)/S phase, and was selected as a promising JAK2/FLT3 dual inhibitor. (C) 2019 Elsevier Masson SAS. All rights reserved.
• 460. Cytotoxic compounds. Part II. Some amides of the “nitrogen mustard” type
  作者：M. H. Benn、A. M. Creighton、L. N. Owen、G. R. White

  DOI：10.1039/jr9610002365

  日期：——
• Discovery of Potent, Selective Stem Cell Factor Receptor/Platelet Derived Growth Factor Receptor Alpha (c-KIT/PDGFRα) Dual Inhibitor for the Treatment of Imatinib-Resistant Gastrointestinal Stromal Tumors (GISTs)
  作者：Yanli Lu、Fei Mao、Xiaokang Li、Xinyu Zheng、Manjiong Wang、Qing Xu、Jin Zhu、Jian Li

  DOI：10.1021/acs.jmedchem.7b00468

  日期：2017.6.22

  Stem cell factor receptor (c-KIT) and platelet derived growth factor receptor alpha (PDGFR alpha) kinasts play an important role in gastrointestinal stromal tumors (GISTs). Here, we have discovered an c-KIT/PDGFR alpha dual inhibitor, compound 31, with single-digit nanomolar potency against c-KIT and PDGFRa. Compared to Imatinib (1), 31 showed better antiproliferative efficacy against various TEL-c-KIT/PD GFR alpha-BaF3 isogenic cells, including three 1-resistant BaF3 cell lines, as well as against GIST-T1 and GIST-882 cell lines. Furthermore, compound 31 showed a good KinomeScan selectivity (468 kinases) (S score (1) = 0.01 at 1 mu M concentration), good metabolic stability in liver microsomes, and no hERG inhibitory activity. It was worth noting that 31 inhibited GIST-T1 tumor growth (TGI = 81.5%) and even the BaF3-TEL-cKIT-T6701 tumor progression (TGI = 41.9%, 1-resistant GISTs) at a dosage of 100 mg/kg/day without exhibiting apparent toxicity.