4-Chloro-2-(pyridin-2-yl)-quinazoline | 91748-47-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4-Chloro-2-(pyridin-2-yl)-quinazoline
• 英文别名: 4-Chloro-2-(pyridin-2-yl)quinazoline；4-chloro-2-pyridin-2-ylquinazoline
• CAS: 91748-47-9
• 化学式: C₁₃H₈ClN₃
• mdl: MFCD03694420
• 分子量: 241.68
• InChiKey: WEQSCSKJHXQJOB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-Chloro-2-(pyridin-2-yl)-quinazoline 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 生成 N-[(2S)-1-oxo-3-phenyl-1-{4-[2-(pyridin-2-yl)quinazolin-4-yl]piperazin-1-yl}propan-2-yl]acetamide
  参考文献：
  名称：

  Pyridinylquinazolines Selectively Inhibit Human Methionine Aminopeptidase-1 in Cells

  摘要：

  Methionine aminopeptidases (MetAPs), which remove the initiator methionine from nascent peptides, are essential in all organisms. While MetAP2 has been demonstrated to be a therapeutic target for inhibiting angiogenesis in mammals, MetAP1 seems to be vital for cell proliferation. Our earlier efforts identified two structural classes of human MetAP1 (HsMetAP1)-selective inhibitors (14), but all of them failed to inhibit cellular HsMetAP1. Using Mn(II) or Zn(II) to activate HsMetAP1, we found that 14 could only effectively inhibit purified HsMetAP1 in the presence of physiologically unachievable concentrations of Co(II). In an effort to seek Co(II)-independent inhibitors, a novel structural class containing a 2-(pyridin-2-yl)quinazoline core has been discovered. Many compounds in this class potently and selectively inhibited HsMetAP1 without Co(II). Subsequently, we demonstrated that 11j, an auxiliary metal-dependent inhibitor, effectively inhibited HsMetAP1 in primary cells. This is the first report that an HsMetAP1-selective inhibitor is effective against its target in cells.

  DOI：

  10.1021/jm400227z
• 作为产物：
  描述：

  2-吡啶甲酰氯 在 sodium methylate 、 N,N-二甲基苯胺 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 42.5h， 生成 4-Chloro-2-(pyridin-2-yl)-quinazoline
  参考文献：
  名称：

  Discovery of Potent Cyclic GMP Phosphodiesterase Inhibitors. 2-Pyridyl- and 2-Imidazolylquinazolines Possessing Cyclic GMP Phosphodiesterase and Thromboxane Synthesis Inhibitory Activities

  摘要：

  Moderate cyclic GMP phosphodiesterase (cGMP-PDE, PDE V) inhibitor 2-phenyl-4-anilino-quinazoline (1) was identified utilizing MultiCASE assisted drug design (MCADD) technology. Modification of compound 1 was conducted at the 2-, 4-, and 6-positions of the quinazoline ring for enhancement of cGMP-PDE inhibitory activity. The 6-substituted 2-(imidazol-1-yl)-quinazolines are 1000 times more potent in in vitro PDE V enzyme assay than the well-known inhibitor zaprinast. The 6-substituted derivatives of 2-(3-pyridyl)quinazoline 84 and 2-(imidazol-1-yl)quinazoline 86 exhibited more than 1000-fold selectivity for PDE V over the other four PDE isozymes. In addition, cGMP-PDE inhibitors 64, 65, and 73 were found to have an additional property of thromboxane synthesis inhibitory activity.

  DOI：

  10.1021/jm00018a014

文献信息

• 4-Anilino-2-pyridylquinazolines and -pyrimidines as Highly Potent and Nontoxic Inhibitors of Breast Cancer Resistance Protein (ABCG2)
  作者：Michael K. Krapf、Jennifer Gallus、Michael Wiese

  DOI：10.1021/acs.jmedchem.7b00441

  日期：2017.5.25

  particular for breast cancer resistance protein (BCRP/ABCG2), there is a persistent need for studies of inhibitors of ABCG2. In this study, we investigated a systematic series of 4-substituted-2-pyridylquinazolines in terms of their inhibitory potency as well as selectivity toward ABCG2. For comparison, the quinazoline scaffold was reduced to the significantly smaller 4-methylpyrimidine basic structure

  由ATP结合盒（ABC）转运蛋白介导的多药耐药性（MDR）仍然是癌症化学治疗中的主要问题，可以通过抑制转运蛋白来克服。由于缺乏了解，特别是对于乳腺癌抗性蛋白（BCRP / ABCG2），转运过程中涉及的复杂机制，一直需要研究ABCG2抑制剂。在这项研究中，我们研究了系统的一系列4-取代的-2-吡啶基喹唑啉，它们具有抑制力以及对ABCG2的选择性。为了比较，将喹唑啉支架还原为明显更小的4-甲基嘧啶基本结构。此外，用化学治疗剂SN-38和米托蒽醌（MX）测试了细胞毒性和逆转MDR的能力。通过比色ATP酶测定法研究了化合物与ABCG2的相互作用。以Hoechst 33342作为荧光染料和ABCG2的底物进行酶动力学研究，以阐明化合物的结合模式。
• Compounds for use in inhibiting HIV capsid assembly
  申请人：Ruprecht-Karls-Universität Heidelberg

  公开号：EP2769723A1

  公开（公告）日：2014-08-27

  The present invention relates to a compound or a pharmaceutically acceptable salt or solvate thereof for use in inhibiting HIV capsid assembly, the compound comprising the core structure wherein E is CR7or S, and wherein f is 0 or 1, and wherein in case E is S, f is 0, and wherein the core structure is at least substituted in 2 and 4 position, and wherein the residue R6 and R7, are, independently of each other, selected from the group consisting of -H, -D, -alkyl, alkoxy, alkenyl, alkynyl, halides, -NO2, - OH, - NH2, -NHR4#, -CN, -S(O)R4#, -SO2R4#, -P(O)R4#R5#, -P(O)(OR4#)R5#, - P(O)(OR4#)(OR5#), -C(O)NR4#R5#, -C(O)SR4#, -C(O)R4#, -C(O)O-R4#, alkoxy and glycol chains; and wherein R6 may optionally form a cyclic residue, with a further substituent present 5 or 6 position, and wherein R4# and R5# are, independently of each other, selected from the group consisting of -H, -alkyl, -alkenyl, - heterocycloalkyl, aryl and heteroaryl.

  本发明涉及一种化合物或其药学上可接受的盐或溶剂，用于抑制HIV壳蛋白组装，所述化合物包括核心结构，其中E为CR7或S，f为0或1，若E为S，则f为0，核心结构至少在2和4位置被取代，残基R6和R7，独立于彼此，选自-H、-D、-烷基、烷氧基、烯基、炔基、卤素、-NO2、-OH、-NH2、-NHR4#、-CN、-S(O)R4#、-SO2R4#、-P(O)R4#R5#、-P(O)(OR4#)R5#、-P(O)(OR4#)(OR5#)、-C(O)NR4#R5#、-C(O)SR4#、-C(O)R4#、-C(O)O-R4#、烷氧基和甘醇链；R6可以选择形成一个环状残基，进一步的取代物位于5或6位置，R4#和R5#，独立于彼此，选自-H、-烷基、-烯基、-杂环烷基、芳基和杂芳基。
• [EN] COMPOUNDS FOR USE IN INHIBITING HIV CAPSID ASSEMBLY<br/>[FR] COMPOSÉS POUR UTILISATION DANS L'INHIBITION DE L'ASSEMBLAGE DE CAPSIDE DE VIH
  申请人：RUPRECHT KARLS UNIVERSITÄT HEIDELBERG

  公开号：WO2014128206A1

  公开（公告）日：2014-08-28

  The present invention relates to a compound or a pharmaceutically acceptable salt or solvate thereof for use in inhibiting HIV capsid assembly, the compound comprising the core structure wherein E is CR7or S, and wherein f is 0 or 1, and wherein in case E is S, f is 0, and wherein the core structure is at least substituted in 2 and 4 position, and wherein the residue R6 and R7, are, independently of each other, selected from the group consisting of -H, -D, -alkyl, alkoxy, alkenyl, alkynyl, halides, -NO2, - OH, -NH2, -NHR4#, -CN, - S(O)R4#, -SO2R4#, -P(O)R4#R5#, -P(O)(OR4#)R5#, -P(O)(OR4#)(OR5#), -C(O)NR4#R5#, - C(O)SR4#, -C(O)R4#, -C(O)O-R4#, alkoxy and glycol chains; and wherein R6 may optionally form a cyclic residue, with a further substituent present 5 or 6 position, and wherein R4# and R5# are, independently of each other, selected from the group consisting of -H, -alkyl, -alkenyl, -heterocyclo alkyl, aryl and heteroaryl.

  本发明涉及一种化合物或其在抑制HIV衣壳组装中的药用盐或溶剂中的使用，该化合物包括核心结构，其中E为CR7或S，其中f为0或1，在E为S的情况下，f为0，在核心结构至少在2和4位置被取代，在残基R6和R7中，它们分别选自-H，-D，-烷基，烷氧基，烯基，炔基，卤素，-NO2，-OH，-NH2，-NHR4#，-CN，-S(O)R4#，-SO2R4#，-P(O)R4#R5#，-P(O)(OR4#)R5#，-P(O)(OR4#)(OR5#)，-C(O)NR4#R5#，-C(O)SR4#，-C(O)R4#，-C(O)O-R4#，烷氧基和甘醇链；其中R6可以选择形成一个环状残基，并在5或6位置存在另一个取代基，而R4#和R5#分别选自-H，-烷基，-烯基，-杂环烷基，芳基和杂芳基。
• Conversion of Quinazoline Modulators from Inhibitors to Activators of β-Glucocerebrosidase
  作者：Jianbin Zheng、Sohee Jeon、Weilan Jiang、Lena F. Burbulla、Daniel Ysselstein、Kristine Oevel、Dimitri Krainc、Richard B. Silverman

  DOI：10.1021/acs.jmedchem.8b01294

  日期：2019.2.14

  work, we present a structure-activity relationship (SAR) study of quinazoline compounds that serve as inhibitors of GCase. Unexpectedly, we found that N-methylation of these inhibitors transformed them into GCase activators. A systematic SAR study further revealed that replacement of the key oxygen atom in the linker of the quinazoline derivative also contributed to the activity switch. PD patient-derived

  高雪氏病是一种溶酶体病，是由β-葡萄糖脑苷脂酶基因（GBA1和GCase）的突变引起的，这些突变也与帕金森氏病（PD）和弥漫性路易氏体痴呆的风险增加有关。先前的研究表明，突变的GCase蛋白会发生错误折叠和降解，因此，突变蛋白的稳定代表了突触核蛋白病的重要治疗策略。在这项工作中，我们提出了作为GCase抑制剂的喹唑啉化合物的构效关系（SAR）研究。出乎意料的是，我们发现这些抑制剂的N-甲基化将它们转化为GCase激活剂。一项系统的SAR研究进一步表明，替换喹唑啉衍生物连接基中的关键氧原子也有助于活性转换。PD患者衍生的成纤维细胞和多巴胺能中脑神经元用选定的化合物（9q）处理，该化合物部分稳定了GCase并提高了其活性。这些结果突出了PD和相关突触核蛋白病中非抑制性GCase调节剂的治疗性开发的新策略。
• Method for inhibiting neoplastic cells and related conditions by exposure to 4-aminoquinazoline derivatives
  申请人：——

  公开号：US20020025968A1

  公开（公告）日：2002-02-28

  A method for inhibiting neoplastic cells and related conditions by exposing them to 4-aminoquinazoline derivatives.

  通过将肿瘤细胞暴露于4-氨基喹噁啉衍生物来抑制肿瘤细胞和相关疾病的方法。