4-氯喹唑啉-2-甲酸乙酯 | 34632-69-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-氯喹唑啉-2-甲酸乙酯
• 中文别名: 乙基4-氯喹唑啉-2-甲酸酯
• 英文名称: ethyl 4-chloroquinazoline-2-carboxylate
• CAS: 34632-69-4
• 化学式: C₁₁H₉ClN₂O₂
• mdl: MFCD04107645
• 分子量: 236.658
• InChiKey: ZMAJSODACDWUAS-UHFFFAOYSA-N

物化性质

• 熔点：
  100-101°C
• 沸点：
  391.3±34.0 °C(Predicted)
• 密度：
  1.341±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  52.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  4-氯喹唑啉-2-甲酸乙酯 在 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、103.42 kPa 条件下， 反应 8.25h， 生成 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(4-quinazoline-2-carboxamido)morphinan
  参考文献：
  名称：

  Design, syntheses, and pharmacological characterization of 17-cyclopropylmethyl-3,14β-dihydroxy-4,5α-epoxy-6α-(isoquinoline-3′-carboxamido)morphinan analogues as opioid receptor ligands

  摘要：

  A series of 17-cyclopropylmethyl-3,14 beta-dihydroxy-4,5 alpha-epoxy-6 alpha-(isoquinoline-3 '-carboxamido)morphinan (NAQ) analogues were synthesized and pharmacologically characterized to study their structure-activity relationship at the mu opioid receptor (MOR). The competition binding assay showed two-atom spacer and aromatic side chain were optimal for MOR selectivity. Meanwhile, substitutions at the 1 '- and/or 4 '-position of the isoquinoline ring retained or improved MOR selectivity over the kappa opioid receptor while still possessing above 20-fold MOR selectivity over the delta opioid receptor. In contrast, substitutions at the 6 '- and/or 7 '-position of the isoquinoline ring reduced MOR selectivity as well as MOR efficacy. Among this series of ligands, compound 11 acted as an antagonist when challenged with morphine in warm-water tail immersion assay and produced less significant withdrawal symptoms compared to naltrexone in morphine-pelleted mice. Compound 11 also antagonized the intracellular Ca2+ increase induced by DAMGO. Molecular dynamics simulation studies of 11 in three opioid receptors indicated orientation of the 6 '-nitro group varied significantly in the different 'address' domains of the receptors and played a crucial role in the observed binding affinities and selectivity. Collectively, the current findings provide valuable insights for future development of NAQ-based MOR selective ligands. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.02.055
• 作为产物：
  描述：

  4-喹唑啉酮-2-甲酸乙酯 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 生成 4-氯喹唑啉-2-甲酸乙酯
  参考文献：
  名称：

  包含1,2,4-三唑并[4,3- a ]吡啶部分的新型喹唑啉硫醚衍生物的合成，晶体结构和农业抗菌性评价

  摘要：

  总共设计，合成和评估了22个结合有1,2,4-三唑并[4,3- a ]吡啶部分的喹唑啉硫醚衍生物，并将其作为农业上的抗菌剂进行了评估。在这些化合物中，通过单晶X射线衍射分析进一步证实了化合物6l的化学结构。生物测定结果表明，某些化合物对被测植物病原菌具有显着的体外抗菌活性。例如，化合物6b和6g的抗轴索黄单胞菌pv的EC 50值低至10.0和24.7μg / mL 。红蜘蛛（西飞），分别比市售农用杀菌剂比美噻唑（56.9μg/ mL）好得多。特别地，还发现化合物6b能够抑制病原细菌米氏黄单胞菌（Xanthomonas oryzae pv）。米曲霉（白叶枯病）约12倍于对照叶枯唑更有效，在其EC方面50的值（7.2对89.8微克/毫升）。重要的是，在该系列中，活性最高的化合物6b证明是具有最高亲水性和最低分子量的化合物。体内生物测定进一步显示了6b作为控制Xoo的有前途的植物杀菌剂的应用前景。。另外，还在50μg/

  DOI：

  10.1021/acs.jafc.9b04733

文献信息

• QUINAZOLINE COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Hadd Michael J.

  公开号：US20120053174A1

  公开（公告）日：2012-03-01

  Provided herein are quinazoline compounds for treatment of JAK kinase mediated diseases, including JAK2 kinase-, JAK3 kinase- or TYK2 kinase-mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.

  本文提供了喹唑啉化合物，用于治疗JAK激酶介导的疾病，包括JAK2激酶、JAK3激酶或TYK2激酶介导的疾病。还提供了包含这些化合物的药物组合物以及使用这些化合物和组合物的方法。
• SUBSTITUTED 2- AMIDOQUINAZOL-4-ONES AS MATRIX METALLOPROTEINASE-13 INHIBITORS
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150329556A1

  公开（公告）日：2015-11-19

  The present invention provides a novel amide derivative having a matrix metalloproteinase inhibitory activity, and useful as a pharmaceutical agent, which is a compound represented by the formula (I) wherein ring A is an optionally substituted, nitrogen containing heterocycle, ring B is an optionally substituted monocyclic homocycle or an optionally substituted monocyclic heterocycle, Z is N or NR 1 (R 1 is a hydrogen atom or an optionally substituted hydrocarbon group), is a single bond or a double bond, R 2 is a hydrogen atom or an optionally substituted hydrocarbon group, X is an optionally substituted spacer having 1 to 6 atoms, ring C is (1) an optionally substituted homocycle or (2) an optionally substituted heterocycle other than a ring represented by (II) (X′ is S, O, SO, or CH 2 ), and at least one of ring B and ring C has substituent(s), provided that N-(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]2 hydroxypropyl}5,6 dimethyl 4 oxo 1,4 dihydrothieno[2,3-d]pyrimidine-2-carboxamide is excluded, or a salt thereof.

  本发明提供了一种新型酰胺衍生物，具有基质金属蛋白酶抑制活性，并且作为药用剂是有用的，该化合物由以下式(I)表示，其中环A是一个可选择取代的含氮杂环，环B是一个可选择取代的单环同核环或可选择取代的单环杂环，Z是N或NR1（R1是氢原子或可选择取代的碳氢基团），是一个单键或双键，R2是氢原子或可选择取代的碳氢基团，X是一个具有1到6个原子的可选择取代的间隔物，环C是（1）一个可选择取代的同核环或（2）一个除了由（II）表示的环之外的可选择取代的杂环（X′是S、O、SO或CH2），并且环B和环C中至少有一个有取代基，但不包括N-(1S,2R)-1-(3,5-二氟苄基)-3-[(3-乙基苄基)氨基]2-羟基丙基}5,6-二甲基-4-氧代-1,4-二氢噻唑并[2,3-d]嘧啶-2-羧酰胺，或其盐。
• Design, Synthesis and Biological Evaluation of Novel Quinazoline-Based Anti-inflammatory Agents Acting as PDE4B Inhibitors
  作者：Rabah Ahmed Taha Serya、Abeer Hussin Abbas、Nasser Saad Mohamed Ismail、Ahmed Esmat、Dalal Abdelrahman Abou El Ella

  DOI：10.1248/cpb.c14-00737

  日期：——

  A novel series of quinzoline based compounds (IIIa–d, VIa–f, IXa–f) were designed, synthesized and screened for their inhibitory activity towards the PDE4B isoform. The in vivo anti-inflammatory effect of the titled compounds (IIIa–d, VIa–f, IXa–f) as well as their effect on the level of tumor necrosis factor (TNF-α) were evaluated. Among all of the synthesized compounds, IXb, IXd and IXf, exhibited good inhibitory activity against PDE4B enzyme with inhibition percentages of 42, 62 and 68%, respectively. Most of the tested compounds showed potent anti-inflammatory activity compared to indomethacin with a marked decrease in TNF-α level. The ulcerogenic effect of the tested compounds was also examined. The gastric mucosa of the tested animals remained intact after oral administration of the hit compounds. Additionally, docking study was used to explore the possible binding mode of the active compounds on the PDE4B enzyme as well as to illustrate the selectivity of the active hits on the PDE4B isoform.

  设计、合成并筛选了一系列基于喹唑啉的化合物（IIIa–d、VIa–f、IXa–f），以评估它们对PDE4B亚型的抑制活性。评估了目标化合物（IIIa–d、VIa–f、IXa–f）的体内抗炎作用及其对肿瘤坏死因子（TNF-α）水平的影响。在所有合成的化合物中，IXb、IXd和IXf对PDE4B酶表现出良好的抑制活性，抑制百分比分别为42％、62％和68％。与吲哚美辛相比，大多数测试化合物显示出强大的抗炎活性，TNF-α水平显著降低。还检查了测试化合物的致溃疡作用。测试动物在接受命中化合物的口服给药后，胃粘膜保持完整。此外，对接研究用于探索活性化合物在PDE4B酶上的可能结合模式，并说明活性命中对PDE4B亚型的选择性。
• [EN] PIPERIDINE SUBSTITUTED PYRAZOLO[1,5-A]PYRIMIDINE DERIVATIVES WITH INHIBITORY ACTIVITY ON THE REPLICATION OF THE RESPIRATORY SYNCYTIAL VIRUS (RSV)<br/>[FR] DÉRIVÉS DE PYRAZOLO[1,5-A]PYRIMIDINE SUBSTITUÉS PAR PIPÉRIDIN, AYANT UNE ACTIVITÉ INHIBITRICE SUR LA RÉPLICATION DU VIRUS RESPIRATOIRE SYNCYTIAL (RSV)
  申请人：JANSSEN SCIENCES IRELAND UC

  公开号：WO2016091774A1

  公开（公告）日：2016-06-16

  The invention concerns novel substituted bicyclic pyrazolo pyrimidine compounds of formula (I) having antiviral activity, in particular, having an inhibitory activity on the replication of the respiratory syncytial virus (RSV). The invention further concerns the preparation of such novel compounds, compositions comprising these compounds, and the compounds for use in the treatment of respiratory syncytial virus infection.

  这项发明涉及具有抗病毒活性的新型取代的双环吡唑嘧啶化合物，特别是对呼吸道合胞病毒（RSV）复制具有抑制活性的化合物。该发明还涉及制备这种新型化合物，包含这些化合物的组合物，以及用于治疗呼吸道合胞病毒感染的化合物。
• ADENOSINE A3 RECEPTOR MODULATING COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Armstrong Robert C.

  公开号：US20120053176A1

  公开（公告）日：2012-03-01

  Provided herein is a method of preventing, treating, or ameliorating one or more symptoms of an adenosine A 3 -mediated condition, disorder, or disease, with a compound of Formula I. Also provided herein is a method of preventing, treating, or ameliorating one or more symptoms of glaucoma or ocular hypertension. Further provided herein is a method of modulating the activity of an adenosine A 3 receptor.

  本文提供了一种预防、治疗或改善腺苷A3介导的疾病、紊乱或疾病的一个或多个症状的方法，使用化合物I的方法。本文还提供了一种预防、治疗或改善青光眼或眼压增高的一个或多个症状的方法。此外，本文还提供了一种调节腺苷A3受体活性的方法。