4-chloro-but-2-enoyl chloride | 24806-06-2

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 酰卤
• 英文名称: 4-chloro-but-2-enoyl chloride
• 英文别名: γ-Chlor-crotonsaeure-chlorid；4-chlorobut-2-enoyl chloride
• CAS: 24806-06-2
• 化学式: C₄H₄Cl₂O
• 分子量: 138.981
• InChiKey: KBQPIDSATRHKJR-UHFFFAOYSA-N

物化性质

• 沸点：
  74-74.5 °C(Press: 16 Torr)
• 密度：
  1.316 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  7
• 可旋转键数：
  2
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  甲醇 、 4-chloro-but-2-enoyl chloride 在 N,N-二乙基苯胺 作用下， 生成 methyl 4-chloro-2-butenoate
  参考文献：
  名称：

  Binon,F. et al., Bulletin des Societes Chimiques Belges, 1963, vol. 72, p. 166 - 177

  摘要：

  DOI：
• 作为产物：
  描述：

  4-chlorocrotonic acid 在 氯化亚砜 作用下， 生成 4-chloro-but-2-enoyl chloride
  参考文献：
  名称：

  Binon,F. et al., Bulletin des Societes Chimiques Belges, 1963, vol. 72, p. 166 - 177

  摘要：

  DOI：

文献信息

• Modified PEG-anilinoquinazoline derivatives as potential EGFR PET agents
  作者：Samar Dissoki、Renana Eshet、Hana Billauer、Eyal Mishani

  DOI：10.1002/jlcr.1569

  日期：2009.2

  Inhibition of epidermal growth factor receptor tyrosine kinase (EGFR-TK) has emerged as a major approach for cancer-targeted therapy. Consequently, there has been a great interest in the use of labeled EGFR-TK inhibitors as positron emission tomography (PET) imaging agents. Currently, the developed agents did not yield adequate PET imaging of animal models probably due to poor solubility, rapid washout from blood, and low stability in vivo. In order to overcome these hurdles, new derivatives of previously reported inhibitors (ML04, 2) with decreased log P and increased solubility were designed and synthesized. These compounds (3–5) exhibited high autophosphorylation inhibitory potency with an IC50 of 5–35 nM, decreased log P's (3.1, 3.34, and 3.45, respectively), and significantly increased solubility (630, 300, and 120 µg/mL, respectively) relative to the previously reported parent compound 2 (log P=3.7, solubility=3.5 µg/mL). The labeling of compound 5 with [18F] and compounds 3 and 4 with [11C] and [124I], respectively, involved a one-step radiosynthesis. Compounds 3–5 were obtained with a total decay-corrected radiochemical yields of 13, 31, and 5%, respectively, and were found to be stable in blood. The positive outcome achieved with compounds 3–5 merits further in vivo evaluation as PET bioprobes. Copyright © 2008 John Wiley & Sons, Ltd.

  表皮生长因子受体酪氨酸激酶(EGFR-TK)的抑制已成为癌症靶向治疗的主要方法。因此,对于使用标记的EGFR-TK抑制剂作为正电子发射断层扫描(PET)成像剂产生了极大的兴趣。目前,开发的代理并未产生充分的动物模型的PET成像,可能由于其较差的溶解性、从血液中快速洗脱和在体内低稳定性。为了克服这些障碍,设计并合成了先前报道的抑制剂(ML04, 2)的新衍生物,这些衍生物具有减小的log P和增加的溶解性。这些化合物(3–5)显示出高的自磷酸化抑制效力,IC50值为5–35 nM,相对先前报道的母体化合物2(log P=3.7,溶解性=3.5 µg/mL),具有减小的log P(分别为3.1,3.34和3.45)和显著增加的溶解性(分别为630,300和120 µg/mL)。化合物5与[18F]、化合物3和4分别与[11C]和[124I]的标记涉及一步放射合成。化合物3–5获得的总衰变校正放射化学产率分别为13%,31%和5%,发现它们在血液中稳定。化合物3–5获得的正面结果值得进一步作为PET生物探针进行体内评估。版权所有 © 2008 John Wiley & Sons, Ltd.
• [EN] INHIBITORS OF C-JUN-N-TERMINAL KINASE (JNK)<br/>[FR] INHIBITEURS DE LA KINASE C-JUN-N-TERMINALE (JNK)
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2013074986A1

  公开（公告）日：2013-05-23

  The present invention provides novel compounds according to Formula (I): where Ring A, Ring B, X, L1, L2, RA, RC, RD, RE, m, n, and p are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of human diseases associated with kinase activity, for example, proliferative diseases, neurodegenerative diseases, metabolic disorders, inflammatory diseases, and cardiovascular diseases.

  本发明提供了根据式（I）的新化合物：其中环A、环B、X、L1、L2、RA、RC、RD、RE、m、n和p如本文所定义。本发明的化合物可用于预防和治疗与激酶活性相关的各种人类疾病，例如增殖性疾病、神经退行性疾病、代谢紊乱、炎症性疾病和心血管疾病。
• Prost,M. et al., Chimica Therapeutica, 1967, vol. 2, p. 133 - 143
  作者：Prost,M. et al.

  DOI：——

  日期：——
• Highly Suppressing Wild-Type HIV-1 and Y181C Mutant HIV-1 Strains by 10-Chloromethyl-11-demethyl-12-oxo-calanolide A with Druggable Profile
  作者：Hai Xue、Xiaofan Lu、Purong Zheng、Li Liu、Chunyan Han、Jinping Hu、Zijie Liu、Tao Ma、Yan Li、Lin Wang、Zhiwei Chen、Gang Liu

  DOI：10.1021/jm901653e

  日期：2010.2.11

  We herein report a new compound: 10-chloromethyl-11-demethyl-12-oxo-calanolide A (20, EC50 = 7.4 nM, St = 1417), which demonstrates a druggable profile with 32.7% oral bioavailability in rat, tolerated oral single dose toxicity in mice, and especially the feature of highly efficient suppression of the wild-type HIV-1 and Y181C mutant HIV-1 at an EC50 = 7.4 nM and EC50 = 0.46 nM, respectively.
• Binon,F. et al., Bulletin des Societes Chimiques Belges, 1963, vol. 72, p. 166 - 177
  作者：Binon,F. et al.

  DOI：——

  日期：——