喹啉,1-(氯乙酰基)-6-氟-1,2,3,4-四氢- | 125579-10-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 喹啉,1-(氯乙酰基)-6-氟-1,2,3,4-四氢-
• 英文名称: 1,2,3,4-tetrahydro-6-fluoro-N-(chloroacetyl)quinoline
• 英文别名: 2-chloro-1-(6-fluoro-3,4-dihydro-1(2H)-quinolinyl)ethanone；2-chloro-1-(6-fluoro-3,4-dihydroquinolin-1(2H)-yl)ethanone；Quinoline, 1-(chloroacetyl)-6-fluoro-1,2,3,4-tetrahydro-；2-chloro-1-(6-fluoro-3,4-dihydro-2H-quinolin-1-yl)ethanone
• CAS: 125579-10-4
• 化学式: C₁₁H₁₁ClFNO
• mdl: MFCD27942583
• 分子量: 227.666
• InChiKey: VTAOQYAHIDMKET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.363
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  喹啉,1-(氯乙酰基)-6-氟-1,2,3,4-四氢- 在 sodium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 40.17h， 生成 C₂₇H₂₄BrF₄N₃O₆S
  参考文献：
  名称：

  Computationally Guided Identification of Allosteric Agonists of the Metabotropic Glutamate 7 Receptor

  摘要：

  The metabotropic glutamate 7 (mGlu(7)) receptor belongs to the group III of mGlu receptors. Since the mGlu(7) receptor can control excitatory neuro-transmission in the hippocampus and cortex, modulation of the receptor may have therapeutic benefit in several CNS diseases. However, mGlu(7) remains relatively unexplored among the eight known mGlu receptors partly because of the limited availability of tool compounds to interrogate its potential therapeutic utility. Here we report the discovery of a new class of mGlu(7) allosteric agonists. Hits originating from virtual screening were followed up with further analogue searching and screening, leading to a novel series of mGlu(7) allosteric agonists. Guided by docking into a structural model of the mGlu(7) receptor the initial hit 5 was successfully optimized to analogues with comparable potencies and more attractive drug-like attributes than AMN082.

  DOI：

  10.1021/acschemneuro.8b00331
• 作为产物：
  描述：

  6-氟-1,2,3,4-四氢喹啉 、 氯乙酰氯 以 苯 为溶剂， 生成 喹啉,1-(氯乙酰基)-6-氟-1,2,3,4-四氢-
  参考文献：
  名称：

  1,2-二氢-1-氧代吡咯并[3,2,1-kl]吩噻嗪-2-羧酰胺和同类物，具有抗炎活性的双重环氧合酶/ 5-脂氧合酶抑制剂。

  摘要：

  一系列1,2-二氢-1-氧杂吡咯[3,2,1-kl]吩噻嗪，1,2-二氢-1-氧杂吡咯[3,2,1-kl]吩恶嗪和1,2-二氢- 1-氧代吡咯并[3,2,1-去] ac啶-2-羧酰胺是通过1,2-二氢-1-氧代-吡咯并[3,2,1-kl]吩噻嗪或其他相应的吩恶嗪与a啶乙基的反应制得的或带有适当胺的甲酯。发现该家族的几个成员是花生四烯酸代谢的有效的环氧合酶和5-脂氧合酶的双重抑制剂，并且在大鼠足水肿试验中具有体内抗炎活性。描述了该化合物家族中的构效关系。1,2-二氢-N-（2-噻唑基）-1-氧吡咯并[3,2，发现1-kl]吩噻嗪-1-羧酰胺（34）是表现出有效的环氧合酶/ 5-脂氧合酶抑制花生四烯酸代谢的最佳化合物之一。它对源自大鼠嗜碱性粒细胞白血病1（RBL-1）细胞的酶的IC50分别为0.07和1.4 microM。它在大鼠足部水肿试验中具有抗炎作用（在33 mg / kg口服时抑制48

  DOI：

  10.1021/jm00169a035

文献信息

• 1,2-Dihydro-1-oxopyrrolo[3,2,1-kl]phenothiazine-2-carboxamides and congeners, dual cyclooxygenase/5-lipoxygenase inhibitors with anti-inflammatory activity
  作者：Banavara L. Mylari、Thomas J. Carty、Peter F. Moore、William J. Zembrowski

  DOI：10.1021/jm00169a035

  日期：1990.7

  A series of 1,2-dihydro-1-oxopyrrolo[3,2,1-kl]phenothiazine, 1,2-dihydro-1-oxopyrrolo[3,2,1-kl]phenoxazine, and 1,2-dihydro-1-oxopyrrolo[3,2,1-de]acridine-2-carboxamides were prepared by reaction of 1,2-dihydro-1-oxo-pyrrolo[3,2,1-kl]phenothiazine or other corresponding phenoxazine and acridan ethyl or methyl esters with appropriate amines. Several members of this family were found to be potent, dual

  一系列1,2-二氢-1-氧杂吡咯[3,2,1-kl]吩噻嗪，1,2-二氢-1-氧杂吡咯[3,2,1-kl]吩恶嗪和1,2-二氢- 1-氧代吡咯并[3,2,1-去] ac啶-2-羧酰胺是通过1,2-二氢-1-氧代-吡咯并[3,2,1-kl]吩噻嗪或其他相应的吩恶嗪与a啶乙基的反应制得的或带有适当胺的甲酯。发现该家族的几个成员是花生四烯酸代谢的有效的环氧合酶和5-脂氧合酶的双重抑制剂，并且在大鼠足水肿试验中具有体内抗炎活性。描述了该化合物家族中的构效关系。1,2-二氢-N-（2-噻唑基）-1-氧吡咯并[3,2，发现1-kl]吩噻嗪-1-羧酰胺（34）是表现出有效的环氧合酶/ 5-脂氧合酶抑制花生四烯酸代谢的最佳化合物之一。它对源自大鼠嗜碱性粒细胞白血病1（RBL-1）细胞的酶的IC50分别为0.07和1.4 microM。它在大鼠足部水肿试验中具有抗炎作用（在33 mg / kg口服时抑制48
• Novel GPR120 Agonists with Improved Pharmacokinetic Profiles for the Treatment of Type 2 Diabetes
  作者：Guoxia Ji、Qinghua Guo、Qidi Xue、Ruifang Kong、Shiben Wang、Kang Lei、Renmin Liu、Xuekun Wang

  DOI：10.3390/molecules26226907

  日期：——

  GPR120 is a promising target for the treatment of type 2 diabetes (T2DM), which is activated by free fatty acids (FFAs) and stimulates the release of glucagon-like peptide-1(GLP-1). GLP-1, as an incretin, can enhance glucose-dependent secretion of insulin from pancreatic beta cells and reduce blood glucose. In this study, a series of novel GPR120 agonists were designed and synthesized to improve the stability and hydrophilicity of the phenylpropanoic acid GPR120 agonist TUG-891. Compound 11b showed excellent GPR120 agonistic activity and pharmacokinetic properties, and could reduce the blood glucose of normal mice in a dose-dependent manner. In addition, no hypoglycemic side effects were observed even at a dose of 100 mg/kg. Moreover, 11b showed good anti-hyperglycemic effects in diet-induced obese (DIO) mice. Molecular simulation illustrated that compound 11b could enter the active site of GPR120 and interact with ARG99. Taken together, the results indicate that compound 11b might be a promising drug candidate for the treatment of T2DM.

  GPR120是治疗2型糖尿病（T2DM）的一个有前途的靶点，它被游离脂肪酸（FFAs）激活，并刺激胰高血糖素样肽-1（GLP-1）的释放。GLP-1作为一种胃肠激素，可以增强胰岛β细胞对葡萄糖依赖的胰岛素分泌，并降低血糖。在这项研究中，设计和合成了一系列新型GPR120激动剂，以改善苯丙酸GPR120激动剂TUG-891的稳定性和亲水性。化合物11b表现出优异的GPR120激动活性和药代动力学特性，并且能够以剂量依赖的方式降低正常小鼠的血糖。此外，即使在100 mg/kg的剂量下也没有观察到低血糖的副作用。此外，11b在饮食诱导性肥胖（DIO）小鼠中显示出良好的抗高血糖作用。分子模拟表明，化合物11b可以进入GPR120的活性位点并与ARG99发生相互作用。综合这些结果，表明化合物11b可能是治疗T2DM的有前途的药物候选物。
• MYLARI, BANAVARA L.;CARTY, THOMAS J.;MOORE, PETER F.;ZEMBROWSKI, WILLIAM +, J. MED. CHEM., 33,(1990) N, C. 2019-2024
  作者：MYLARI, BANAVARA L.、CARTY, THOMAS J.、MOORE, PETER F.、ZEMBROWSKI, WILLIAM +

  DOI：——

  日期：——
• Selective and antagonist-dependent µ-opioid receptor activation by the combination of 2-{[2-(6-chloro-3,4-dihydro-1(2H)-quinolinyl)-2-oxoethyl]sulfanyl}-5-phenyl-4,6-(1H,5H)-pyrimidinedione and naloxone/naltrexone
  作者：Shu-Yu Lin、Ya-Wen Tien、Yi-Yu Ke、Yung-Chiao Chang、Hsiao-Fu Chang、Li-Chin Ou、Ping-Yee Law、Jing-Hua Xi、Pao-Luh Tao、Horace H. Loh、Yu-Sheng Chao、Chuan Shih、Chiung-Tong Chen、Shiu-Hwa Yeh、Shau-Hua Ueng

  DOI：10.1016/j.bioorg.2022.105905

  日期：2022.11
• US5403839A
  申请人：——

  公开号：US5403839A

  公开（公告）日：1995-04-04