4-氯-6-氟-喹啉-3-甲腈 | 886362-73-8

• 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: 4-氯-6-氟-喹啉-3-甲腈
• 中文别名: 4-氯-6-氟喹啉-3-甲腈
• 英文名称: 4-chloro-6-fluoroquinoline-3-carbonitrile
• CAS: 886362-73-8
• 化学式: C₁₀H₄ClFN₂
• 分子量: 206.607
• InChiKey: OKGBGMNVXKHICZ-UHFFFAOYSA-N

物化性质

• 沸点：
  351.7±37.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933499090

反应信息

• 作为反应物：
  描述：

  4-氯-6-氟-喹啉-3-甲腈 在 N-甲基吡咯烷酮 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 VU0619858
  参考文献：
  名称：

  Discovery of a novel, CNS penetrant M4 PAM chemotype based on a 6-fluoro-4-(piperidin-1-yl)quinoline-3-carbonitrile core

  摘要：

  This Letter details the discovery and subsequent optimization of a novel M-4 PAM scaffold based on an 6fluoro-4-(piperidin-1-yl) quinoline-3-carbonitrile core, which represents a distinct departure from the classical M4 PAM chemotypes. Optimized compounds in this series demonstrated improved M-4 PAM potency on both human and rat M-4 (4 to 5-fold relative to HTS hit), and displayed attractive physicochemical and DMPK profiles, including good CNS penetration (rat brain: plasma K-p = 5.3, K-p,K-uu = 2.4; MDCK-MDR1 (P-gp) ER = 1.1). (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.08.043
• 作为产物：
  描述：

  2-氨基-5-氟苯甲酸 在 正丁基锂 、 三氯氧磷 作用下， 以 四氢呋喃 、 甲醇 、 benzine 、 正己烷 为溶剂， 反应 3.0h， 生成 4-氯-6-氟-喹啉-3-甲腈
  参考文献：
  名称：

  Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu₇ Positive Allosteric Modulator Tool Compound

  摘要：

  Herein, we report the discovery of the first selective and CNS penetrant mGlu(7) PAM (VU6027459) derived from a "molecular switch" within a selective mGlu(7) NAM chemotype. VU6027459 displayed CNS penetration in both mice (K-p = 2.74) and rats (K-p = 4.78), it was orally bioavailable in rats (%F = 69.5), and undesired activity at DAT was ablated.

  DOI：

  10.1021/acsmedchemlett.0c00432

文献信息

• [EN] 3-AMINOTHIENO[3,2-c]QUINOLINE DERIVATIVES, METHODS OF PREPARATION AND USES<br/>[FR] DÉRIVÉS DE 3-AMINOTHIENO[3,2-C]QUINOLINE, PROCÉDÉS DE PRÉPARATION ET UTILISATIONS
  申请人：UNIV TEMPLE

  公开号：WO2013142010A1

  公开（公告）日：2013-09-26

  The present invention relates to compounds according to Formula I: and salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, X, and Y are as defined herein. Methods for preparing compounds of Formula I are also provided. The present invention further includes methods of treating cellular proliferative disorders, such as cancer, with the compounds of Formula I.

  本发明涉及按照以下式I的化合物及其盐，其中R1、R2、R3、R4、R5、R6、R7、X和Y如本文所定义。还提供了制备式I化合物的方法。本发明还包括使用式I化合物治疗细胞增殖性疾病，如癌症的方法。
• Design and Analysis of the 4‐Anilinoquin(az)oline Kinase Inhibition Profiles of GAK/SLK/STK10 Using Quantitative Structure‐Activity Relationships
  作者：Christopher R. M. Asquith、Tuomo Laitinen、James M. Bennett、Carrow I. Wells、Jonathan M. Elkins、William J. Zuercher、Graham J. Tizzard、Antti Poso

  DOI：10.1002/cmdc.201900521

  日期：2020.1.7

  have been associated with negative clinical outcomes. We have designed and synthesized a series of 4-anilinoquin(az)olines in order to better understand the structure-activity relationships of three main collateral kinase targets of quin(az)oline-based kinase inhibitors: cyclin G associated kinase (GAK), STE20-like serine/threonine-protein kinase (SLK) and serine/threonine-protein kinase 10 (STK10)

  4-苯胺基喹啉和4-苯胺基喹唑啉环系统一直是现有激酶药物发现计划中的重大工作重点，这些计划已开发出获批的药物。随着先进的筛选技术的出现，现在已经评估了这些化合物的广泛的动力学特征。这些环系统最初是为包括表皮生长因子受体（EGFR）在内的特定靶标设计的，但实际上显示了许多有效的附带激酶靶标，其中一些与阴性临床结局有关。我们设计和合成了一系列4-苯胺基喹啉（az）脯氨酸，以便更好地了解基于喹（唑啉的激酶抑制剂的三个主要附带激酶靶的结构-活性关系：细胞周期蛋白G相关激酶（GAK），STE20样丝氨酸/苏氨酸蛋白激酶（SLK）和丝氨酸/苏氨酸蛋白激酶10（STK10）。这是通过一系列定量构效关系（QSAR）分析，激酶ATP结合位点的水位分析以及广泛的小分子X射线结构分析实现的。
• 3-AMINOTHIENO[3,2-c]QUINOLINE DERIVATIVES, METHODS OF PREPARATION AND USES
  申请人：TEMPLE UNIVERSITY - OF THE COMMONWEALTH SYSTEM OF HIGHER EDUCATION

  公开号：US20150065499A1

  公开（公告）日：2015-03-05

  The present invention relates to compounds according to Formula I: and salts thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , X, and Y are as defined herein. Methods for preparing compounds of Formula I are also provided. The present invention further includes methods of treating cellular proliferative disorders, such as cancer, with the compounds of Formula I.

  本发明涉及公式I的化合物及其盐，其中R1，R2，R3，R4，R5，R6，R7，X和Y如本文所定义。本发明还提供了制备公式I化合物的方法。本发明还包括使用公式I化合物治疗细胞增殖性疾病，如癌症的方法。
• Synthesis and cytotoxicity studies of quinoline-3-carbonitrile derivatives
  作者：Shu Lan Zhang、Xin Zhai、Shi Jiao Zhang、Hong Hao Yu、Ping Gong

  DOI：10.1016/j.cclet.2010.03.016

  日期：2010.8

  A series of quinoline-3-carbonitrile derivatives were designed and synthesized. Their cytotoxicity in vitro against four cancer cell lines (A549, HT-29, MDA-MB-231 and SMMC-7721) were evaluated by standard MTT assay. The pharmacological results showed that most of the prepared compounds displayed excellent selective cytotoxicity toward SMMC-7721 cell line. Among them, compounds 7c, 7e, 11b, 11f and 11g were more active than Gefitinb against SMMC-7721 cell line. (C) 2010 Ping Gong. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
• Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu₇ Positive Allosteric Modulator Tool Compound
  作者：Carson W. Reed、Jacob J. Kalbfleisch、Madison J. Wong、Jordan P. Washecheck、Ashton Hunter、Alice L. Rodriguez、Anna L. Blobaum、P. Jeffrey Conn、Colleen M. Niswender、Craig W. Lindsley

  DOI：10.1021/acsmedchemlett.0c00432

  日期：2020.9.10

  Herein, we report the discovery of the first selective and CNS penetrant mGlu(7) PAM (VU6027459) derived from a "molecular switch" within a selective mGlu(7) NAM chemotype. VU6027459 displayed CNS penetration in both mice (K-p = 2.74) and rats (K-p = 4.78), it was orally bioavailable in rats (%F = 69.5), and undesired activity at DAT was ablated.