2-chloro-3-(1-cyanocyclopropyl)benzoic acid chloride | 1125632-92-9

• 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: 2-chloro-3-(1-cyanocyclopropyl)benzoic acid chloride
• 英文别名: 2-Chloro-3-(1-cyanocyclopropyl)benzoyl chloride；2-chloro-3-(1-cyanocyclopropyl)benzoyl chloride
• CAS: 1125632-92-9
• 化学式: C₁₁H₇Cl₂NO
• 分子量: 240.089
• InChiKey: GLXMEDSDMLFEAP-UHFFFAOYSA-N

物化性质

• 沸点：
  394.9±42.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  40.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-3-(1-cyanocyclopropyl)benzoic acid chloride 在 铁粉 、 碳酸氢钠 、 potassium carbonate 、 溶剂黄146 、 calcium chloride 作用下， 以 四氢呋喃 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.75h， 生成 N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2-fluorophenyl}-2-chloro-3-(1-cyanocyclopropyl)benzamide
  参考文献：
  名称：

  Design and Synthesis of Novel DFG-Out RAF/Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Inhibitors. 1. Exploration of [5,6]-Fused Bicyclic Scaffolds

  摘要：

  To develop RAF/VEGFR2 inhibitors that bind to the inactive DFG-out conformation, we conducted structure-based drug design using the X-ray cocrystal structures of BRAF, starting from an imidazo[1,2-b]pyridazine derivative. We designed various [5,6]-fused bicyclic scaffolds (ring A, 1-6) possessing an anilide group that forms two hydrogen bond interactions with Cys532. Stabilizing the planarity of this anilide and the nitrogen atom on the six-membered ring of the scaffold was critical for enhancing BRAF inhibition. The selected [1,3]thiazolo[5,4-b]pyridine derivative 6d showed potent inhibitory activity in both BRAF and VEGFR2. Solid dispersion formulation of 6d (6d-SD) maximized its oral absorption in rats and showed significant suppression of ERK1/2 phosphorylation in an A375 melanoma xenograft model in rats by single administration. Tumor regression (T/C = -7.0%) in twice-daily repetitive studies at a dose of 50 mg/kg in rats confirmed that 6d is a promising RAF/VEGFR2 inhibitor showing potent anticancer activity.

  DOI：

  10.1021/jm300126x
• 作为产物：
  描述：

  2-氯-3-甲基苯甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 氯化亚砜 、 lithium hydroxide monohydrate 、 偶氮二异丁腈 、 水 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 乙腈 、 mineral oil 为溶剂， 反应 61.33h， 生成 2-chloro-3-(1-cyanocyclopropyl)benzoic acid chloride
  参考文献：
  名称：

  Design and Synthesis of Novel DFG-Out RAF/Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) Inhibitors. 1. Exploration of [5,6]-Fused Bicyclic Scaffolds

  摘要：

  To develop RAF/VEGFR2 inhibitors that bind to the inactive DFG-out conformation, we conducted structure-based drug design using the X-ray cocrystal structures of BRAF, starting from an imidazo[1,2-b]pyridazine derivative. We designed various [5,6]-fused bicyclic scaffolds (ring A, 1-6) possessing an anilide group that forms two hydrogen bond interactions with Cys532. Stabilizing the planarity of this anilide and the nitrogen atom on the six-membered ring of the scaffold was critical for enhancing BRAF inhibition. The selected [1,3]thiazolo[5,4-b]pyridine derivative 6d showed potent inhibitory activity in both BRAF and VEGFR2. Solid dispersion formulation of 6d (6d-SD) maximized its oral absorption in rats and showed significant suppression of ERK1/2 phosphorylation in an A375 melanoma xenograft model in rats by single administration. Tumor regression (T/C = -7.0%) in twice-daily repetitive studies at a dose of 50 mg/kg in rats confirmed that 6d is a promising RAF/VEGFR2 inhibitor showing potent anticancer activity.

  DOI：

  10.1021/jm300126x

文献信息

• [EN] METHODS AND COMPOSITIONS OF NOVEL TRIAZINE COMPOUNDS<br/>[FR] METHODES ET COMPOSITIONS A BASE DE NOUVEAUX COMPOSES DE TRIAZINE
  申请人：REDDY US THERAPEUTICS INC

  公开号：WO2004026844A1

  公开（公告）日：2004-04-01

  The present invention relates to methods and compositions comprising compounds that treat pathophysiological conditions arising from inflammatory responses. In particular, the present invention is directed to compounds that inhibit or block glycated protein produced induction of the signaling-associated inflammatory response in endothelial cells. The present invention relates to compounds that inhibit smooth muscle proliferation. In particular, the present invention is directed to compounds that inhibit smooth muscle cell proliferation by modulating HSPGs such as Perlecan. The present invention further relates to the use of compounds to treat vascular occlusive conditions characterized by smooth muscle proliferation such as restenosis and atherosclerosis.

  本发明涉及包含治疗由炎症反应引起的病理生理状况的化合物的方法和组合物。特别是，本发明涉及抑制或阻断在内皮细胞中由糖化蛋白产生的与信号传递相关的炎症反应的化合物。本发明还涉及抑制平滑肌细胞增殖的化合物。特别是，本发明涉及通过调节诸如Perlecan的HSPGs来抑制平滑肌细胞增殖的化合物。本发明进一步涉及使用化合物来治疗由平滑肌增殖特征的心血管闭塞性状况，如再狭窄和动脉粥样硬化。
• [EN] BENZOTHIAZOLE DERIVATIVES AS ANTICANCER AGENTS<br/>[FR] DÉRIVÉS DE BENZOTHIAZOLE CONVENANT COMME AGENTS ANTICANCÉREUX
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010064722A1

  公开（公告）日：2010-06-10

  Provided is a fused heterocycle derivative showing a strong Raf inhibitory activity. A compound represented by the formula (I) wherein each symbol is as defined in the present specification, or a salt thereof.

  提供了一个显示强烈Raf抑制活性的融合杂环衍生物。一个由式(I)表示的化合物，其中每个符号如本说明书中所定义，或其盐。
• [EN] SUBSTITUTED TRIAZINE BMI-1 INHIBITORS<br/>[FR] INHIBITEURS DE BMI-1 DE TYPE TRIAZINE SUBSTITUÉE
  申请人：PTC THERAPEUTICS INC

  公开号：WO2015076801A1

  公开（公告）日：2015-05-28

  Amine substituted triazine compounds and forms thereof that inhibit the function and reduce the level of B-cell specific Moloney murine leukemia virus integration site 1 (Bmi-1) protein and methods for their use to inhibit Bmi- 1 function and reduce the level of Bmi- 1 to treat a cancer mediated by Bmi-1 are described herein.

  本文描述了替代三嗪化合物及其衍生物，其抑制B细胞特异性Moloney小鼠白血病病毒整合位点1（Bmi-1）蛋白的功能并降低其水平，以及用于抑制Bmi-1功能和降低Bmi-1水平以治疗由Bmi-1介导的癌症的方法。
• Design and synthesis of novel DFG-out RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors: 2. Synthesis and characterization of a novel imide-type prodrug for improving oral absorption
  作者：Masanori Okaniwa、Takashi Imada、Tomohiro Ohashi、Tohru Miyazaki、Takeo Arita、Masato Yabuki、Akihiko Sumita、Shunichirou Tsutsumi、Keiko Higashikawa、Terufumi Takagi、Tomohiro Kawamoto、Yoshitaka Inui、Sei Yoshida、Tomoyasu Ishikawa

  DOI：10.1016/j.bmc.2012.06.015

  日期：2012.8

  the oral absorption of thiazolo[5,4-b]pyridine 1, we investigated novel N-acyl imide prodrugs of 1 as RAF/vascular endothelial growth factor receptor 2 (VEGFR2) inhibitors. Introducing N-acyl promoieties at the benzanilide position gave chemically stable imides. N-tert-Butoxycarbonyl (Boc) introduced imide 6 was a promising prodrug, which was converted to the active compound 1 after its oral administration

  作为以前报道的用于增强噻唑并[5,4- b ]吡啶1口服吸收的固体分散体制剂的替代品，我们研究了新型的N-酰基酰亚胺前药1作为RAF /血管内皮生长因子受体2（VEGFR2）抑制剂。在苯甲酰苯胺位置上引入N-酰基基团得到化学稳定的酰亚胺。ñ -叔丁氧羰基（BOC）引入酰亚胺6是一个有希望的前药，将其转化为活性化合物1在小鼠中其口服给药后。6与AcOH（6b的共晶体）具有良好的理化性质，具有中等的热力学溶解度（19μg/ mL）。在小鼠，大鼠，狗和猴子中口服吸收后，该结晶前药6b迅速被酶促转化为1。前药6b 在大鼠A375黑色素瘤异种移植模型中显示了体内抗肿瘤退化功效（T / C = -6.4％）。因此，我们选择6b作为有前途的候选者，并正在进行进一步的研究。在这里，我们报告新型酰亚胺型前药的设计，合成和表征。
• [EN] POLYUREA COPOLYMER<br/>[FR] COPOLYMÈRE DE POLYURÉE
  申请人：BASF SE

  公开号：WO2021122472A1

  公开（公告）日：2021-06-24

  The presently claimed invention is directed to a polyurea copolymer obtained by reacting an isocyanate mixture and at least one at least one secondary amine having at least two amine functionalities; wherein the isocyanate mixture (A) has an average NCO functionality of ≥ 2.10.

  目前所声称的发明涉及通过反应异氰酸酯混合物和至少一种具有至少两个胺官能团的次要胺之一来获得聚氨酯脲共聚物；其中异氰酸酯混合物（A）的平均NCO官能度≥2.10。