2-氰基-5-苄氧基嘧啶 | 166672-22-6

• 物质功能分类: 医药中间体 - 杂环化合物 - 嘧啶类化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-氰基-5-苄氧基嘧啶
• 中文别名: 5-(苄氧基)嘧啶-2-甲腈
• 英文名称: 5-benzyloxypyrimidine-2-carbonitrile
• 英文别名: 5-benzyloxy-2-cyano-pyrimidine；2-cyano-5-benzyloxypyrimidine；5-(Benzyloxy)pyrimidine-2-carbonitrile；5-phenylmethoxypyrimidine-2-carbonitrile
• CAS: 166672-22-6
• 化学式: C₁₂H₉N₃O
• 分子量: 211.223
• InChiKey: IGWUAUDJTKKCAB-UHFFFAOYSA-N

物化性质

• 密度：
  1.25±0.1 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  58.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-氰基-5-苄氧基嘧啶 在 palladium 10% on activated carbon 、 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 36.0h， 生成 2-氰基-5-羟基嘧啶
  参考文献：
  名称：

  Synthesis and Evaluation of Heterocyclic Analogues of Bromoxynil

  摘要：

  One attractive strategy to discover more active and/or crop-selective herbicides is to make structural changes to currently registered compounds. This strategy is especially appealing for those compounds with limited herbicide resistance and whose chemistry is accompanied with transgenic tools to enable herbicide tolerance in crop plants. Bromoxynil is a photosystem II (PSII) inhibitor registered for control of broadleaf weeds in several agronomic and specialty crops. Recently at the University of Tennessee-Knoxville several analogues of bromoxynil were synthesized including a previously synthesized pyridine (2,6-dibromo-5-hydroxypyridine-2-carbonitrile sodium salt), a novel pyrimidine (4,6-dibromo-5-hydroxypyrimidine-2-carbonitrile sodium salt), and a novel pyridine N-oxide (2,6-dibromo-1-oxidopyridin-1-ium-4-carbonitrile). These new analogues of bromoxynil were also evaluated for their herbicidal activity on soybean (Glycine max), cotton (Gossypium hirsutum), redroot pigweed (Amaranthus retroflexus), velvetleaf (Abutilon theophrasti), large crabgrass (Digitaria sanguinalis), and pitted morningglory ( Ipomoea lacunose ) when applied at 0.28 kg ha(-1). A second study was conducted on a glyphosate-resistant weed (Amaranthus palmeri) with the compounds being applied at 0.56 kg ha(-1). Although all compounds were believed to inhibit PSII by binding in the quinone binding pocket of D1, the pyridine and pyridine-N-oxide analogues were clearly more potent than bromoxynil on Amaranthus retroflexus. However, application of the pyrimidine herbicide resulted in the least injury to all species tested. These variations in efficacy were investigated using molecular docking simulations, which indicate that the pyridine analogue may form a stronger hydrogen bond in the pocket of the D1 protein than the original bromoxynil. A pyridine analogue was able to control the glyphosate-resistant Amaranthus palmeri with >80% efficacy. The pyridine analogues of bromoxynil showed potential to have a different weed control spectrum compared to bromoxynil. A pyridine analogue of bromoxynil synthesized in this research controlled several weed species greater than bromoxynil itself, potentially due to enhanced binding within the PSII binding pocket. Future research should compare this analogue to bromoxynil using optimized formulations at higher application rates.

  DOI：

  10.1021/jf404209d
• 作为产物：
  描述：

  5-苄氧基-2-甲基磺酰基嘧啶 、 氰化钾 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以62%的产率得到2-氰基-5-苄氧基嘧啶
  参考文献：
  名称：

  取代的5-（芳基羰基氧基）-2（对氰基苯基）嘧啶的合成及液晶性质

  摘要：

  DOI：

  10.1007/bf01373550

文献信息

• Design, Synthesis, and Biological Evaluation of Novel Pyrimido[4,5-<i>b</i>]indole Derivatives Against Gram-Negative Multidrug-Resistant Pathogens
  作者：Qidi Kong、Wei Pan、Heng Xu、Yaru Xue、Bin Guo、Xin Meng、Cheng Luo、Ting Wang、Shuhua Zhang、Yushe Yang

  DOI：10.1021/acs.jmedchem.1c00621

  日期：2021.6.24

  potent activity against Gram-negative pathogens have been reported. Among them, pyrimido[4,5-b]indole derivatives represented by GP-1 demonstrated excellent broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria but were limited by hERG inhibition and poor pharmacokinetics profile. To improve their drug-like properties, we designed a series of novel pyrimido[4,5-b]indole

  由于革兰氏阴性细菌膜的渗透性差和细菌外排机制麻烦，因此仅报道了少数对革兰氏阴性病原体具有有效活性的 GyrB/ParE 抑制剂。其中，以GP-1为代表的嘧啶并[4,5- b ]吲哚衍生物对革兰氏阳性菌和革兰氏阴性菌均表现出优异的广谱抗菌活性，但受到hERG抑制和较差的药代动力学特征的限制。为了改善它们的类药物特性，我们设计了一系列基于 GP-1 的三环支架和阿卡沙星的 C-7 部分的新型嘧啶并 [4,5- b ] 吲哚衍生物。这些努力最终导致了有希望的化合物18r的发现减少 hERG 责任和改善 PK 概况。化合物18R表现出优异的广谱体外相比GP-1的抗菌活性，包括各种临床耐药的G -病原体，尤其是鲍曼不动杆菌，并且在体内的功效还证实在中性粒细胞减少一个小鼠感染的多药大腿模型耐药鲍曼不动杆菌。
• 一种5-羟基嘧啶-2-羧酸的合成方法
  申请人：上海毕得医药科技有限公司

  公开号：CN103880757B

  公开（公告）日：2016-02-24

  本发明公开了一种5-羟基嘧啶-2-羧酸的合成方法。该合成方法为：将5-溴-2-氰基嘧啶与苯甲醇反应生成5-苄氧基-2-氰基嘧啶；然后5-苄氧基-2-氰基嘧啶在碱性条件下进行反应，再通过对反应液进行酸调节使产物析出，对析出的固体过滤干燥后，即获得目标化合物5-羟基嘧啶-2-羧酸。本发明的主要有益效果为：设计了5-羟基嘧啶-2-羧酸的合成路线，提供了该化合物的制备方法。
• 吲哚并嘧啶三环类化合物及其制备方法和用途
  申请人：中国科学院上海药物研究所

  公开号：CN114763357B

  公开（公告）日：2024-06-18

  本发明公开了一类吲哚并嘧啶三环类化合物及其制备方法和用途，本发明的吲哚并嘧啶三环类化合物的结构如式I所示，式中，各取代基的定义如说明书和权利要求书中所述。本发明的吲哚并嘧啶三环类化合物，体外抗菌活性、hERG毒性和药物代谢性质明显优于GP‑1的一系列螺嘧啶三酮类化合物，适合作为抗菌药物用于人或动物的细菌感染疾病的治疗。#imgabs0#
• Synthesis and liquid crystal properties of substituted 5-(arylcarbonyloxy)-2(p-cyanophenyl)pyrimidines
  作者：M. A. Mikhaleva、G. A. Igonina、V. A. Savel'ev

  DOI：10.1007/bf01373550

  日期：1995.3
• Synthesis and Evaluation of Heterocyclic Analogues of Bromoxynil
  作者：Matthew A. Cutulle、Gregory R. Armel、James T. Brosnan、Michael D. Best、Dean A. Kopsell、Barry D. Bruce、Heidi E. Bostic、Donovan S. Layton

  DOI：10.1021/jf404209d

  日期：2014.1.15

  One attractive strategy to discover more active and/or crop-selective herbicides is to make structural changes to currently registered compounds. This strategy is especially appealing for those compounds with limited herbicide resistance and whose chemistry is accompanied with transgenic tools to enable herbicide tolerance in crop plants. Bromoxynil is a photosystem II (PSII) inhibitor registered for control of broadleaf weeds in several agronomic and specialty crops. Recently at the University of Tennessee-Knoxville several analogues of bromoxynil were synthesized including a previously synthesized pyridine (2,6-dibromo-5-hydroxypyridine-2-carbonitrile sodium salt), a novel pyrimidine (4,6-dibromo-5-hydroxypyrimidine-2-carbonitrile sodium salt), and a novel pyridine N-oxide (2,6-dibromo-1-oxidopyridin-1-ium-4-carbonitrile). These new analogues of bromoxynil were also evaluated for their herbicidal activity on soybean (Glycine max), cotton (Gossypium hirsutum), redroot pigweed (Amaranthus retroflexus), velvetleaf (Abutilon theophrasti), large crabgrass (Digitaria sanguinalis), and pitted morningglory ( Ipomoea lacunose ) when applied at 0.28 kg ha(-1). A second study was conducted on a glyphosate-resistant weed (Amaranthus palmeri) with the compounds being applied at 0.56 kg ha(-1). Although all compounds were believed to inhibit PSII by binding in the quinone binding pocket of D1, the pyridine and pyridine-N-oxide analogues were clearly more potent than bromoxynil on Amaranthus retroflexus. However, application of the pyrimidine herbicide resulted in the least injury to all species tested. These variations in efficacy were investigated using molecular docking simulations, which indicate that the pyridine analogue may form a stronger hydrogen bond in the pocket of the D1 protein than the original bromoxynil. A pyridine analogue was able to control the glyphosate-resistant Amaranthus palmeri with >80% efficacy. The pyridine analogues of bromoxynil showed potential to have a different weed control spectrum compared to bromoxynil. A pyridine analogue of bromoxynil synthesized in this research controlled several weed species greater than bromoxynil itself, potentially due to enhanced binding within the PSII binding pocket. Future research should compare this analogue to bromoxynil using optimized formulations at higher application rates.