1,2,3 trimethoxy-5-(prop-2-yn-1-yl)benzene | 931103-01-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1,2,3 trimethoxy-5-(prop-2-yn-1-yl)benzene
• 英文别名: 1,2,3-trimethoxy-5-(2-propynyl)benzene；1,2,3-Trimethoxy-5-(prop-2-ynyl)benzene；1,2,3-trimethoxy-5-prop-2-ynylbenzene
• CAS: 931103-01-4
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: KYVDMJSJIYTYOO-UHFFFAOYSA-N

物化性质

• 沸点：
  274.6±35.0 °C(Predicted)
• 密度：
  1.060±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  27.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,2,3 trimethoxy-5-(prop-2-yn-1-yl)benzene 、 环己烷基甲醛 在 (S)-(+)-alpha,alpha-二苯基脯氨醇 、 copper(I) bromide 、 zinc dibromide 作用下， 以 1,4-二氧六环 为溶剂， 反应 24.0h， 以50%的产率得到(R)-1-cyclohexyl-4-(3,4,5-trimethoxyphenyl)buta-1,2-diene
  参考文献：
  名称：

  双核金催化丙二烯环化反应不对称构筑六元环

  摘要：

  一种用于通过金催化6-合成的1,4- dihydroarenes简单且有效的方法内苄丙二烯的环化得到了发展。此外，已认识到对映体富集的烯的不对称加氢芳基化反应为包含手性立体中心的芳环稠合六元环（如1,4-二氢萘，1,4-二氢二苯并[ b，d ]噻吩，和双核[（dppm）Au 2 Cl 2施加4,7-二氢苯并[ b ]噻吩[dppm ＝亚甲基双（二苯基膦）]与AgOTf组合作为催化剂，以确保手性转移的高效率。ESI-MS已成功用于表征某些关键的反应性双核金中间体。

  DOI：

  10.1002/chem.201503179
• 作为产物：
  描述：

  3,4,5-三甲氧基苯乙酸 在 lithium aluminium tetrahydride 、 potassium carbonate 、 戴斯-马丁氧化剂 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 1,2,3 trimethoxy-5-(prop-2-yn-1-yl)benzene
  参考文献：
  名称：

  Highly Efficient Ligands for Dihydrofolate Reductase from Cryptosporidium hominis and Toxoplasma gondii Inspired by Structural Analysis

  摘要：

  The search for effective therapeutics for cryptosporidiosis and toxoplasmosis has led to the discovery of novel inhibitors of dihydrofolate reductase (DHFR) that possess high ligand efficiency: compounds with high potency and low molecular weight. Detailed analysis of the crystal structure of dihydrofolate reductase-thymidylate synthase from Cryptosporidium hominis and a homology model of DHFR from Toxoplasma gondii inspired the synthesis of a new series of compounds with a propargyl-based linker between a substituted 2,4-diaminopyrimidine and a trimethoxyphenyl ring. An enantiomerically pure compound in this series exhibits IC50 values of 38 and 1 nM against C. hominis and T. gondii DHFR, respectively. Improvements of 368-fold or 5714-fold (C. hominis and T. gondii) relative to trimethoprim were generated by synthesizing just 14 new analogues and by adding only a total of 52 Da to the mass of the parent compound, creating an efficient ligand as an excellent candidate for further study.

  DOI：

  10.1021/jm061027h

文献信息

• Inhibitors of Dihydrofolate Reductase With Antibacterial Antiprotozoal, Antifungal and Anticancer Properties
  申请人：Anderson Amy C.

  公开号：US20090105287A1

  公开（公告）日：2009-04-23

  The compositions and methods described herein discloses the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus , fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii . These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

  本文描述的组合物和方法揭示了设计、合成和测试作为DHFR抑制剂的化合物。这些抑制剂的基本骨架包括一个2,4-二氨基嘧啶环，带有一个丙炔基连接到另一个取代芳基、双环或杂环芳基环。这些DHFR抑制剂对许多不同的病原体具有强大的选择性作用，包括来自细菌如炭疽芽胞杆菌和耐甲氧西林金黄色葡萄球菌、真菌如白色假丝酵母、白念珠菌和新生隐球菌，以及原虫如人类隐孢子虫和弓形虫的DHFR酶。这些化合物和其他类似化合物也对哺乳动物酶具有强大的作用，可能有助于作为抗癌治疗药物。
• Direct Substitution of Arylalkynyl Carbinols Provides Access to Diverse Terminal Acetylene Building Blocks
  作者：Narendran G-Dayanandan、Eric W. Scocchera、Santosh Keshipeddy、Heather F. Jones、Amy C. Anderson、Dennis L. Wright

  DOI：10.1021/acs.orglett.6b03438

  日期：2017.1.6

  trimethoprim-resistant bacteria, synthetic methods were needed to prepare a diverse array of 3-aryl-propynes with various substitutions at the propargyl position. A direct route was sought whereby nucleophilic addition of acetylene to aryl carboxaldehydes would be followed by reduction or substitution of the resulting propargyl alcohol. The direct reduction, methylation, and dimethylation of these readily available

  为了开发用于抗甲氧苄啶的细菌的下一代抗叶酸药物，需要合成方法来制备在炔丙基位置具有各种取代基的3-芳基丙炔的不同阵列。寻求直接途径，其中将乙炔亲核加成至芳基甲醛中，然后还原或取代所得炔丙醇。这些容易获得的醇类的直接还原，甲基化和二甲基化可有效利用这种罕见的功能阵列。另外，在炔丙基醇的还原中观察到不寻常的硅烷交换反应。
• Synthetic and Crystallographic Studies of a New Inhibitor Series Targeting <i>Bacillus anthracis</i> Dihydrofolate Reductase
  作者：Jennifer M. Beierlein、Kathleen M. Frey、David B. Bolstad、Phillip M. Pelphrey、Tammy M. Joska、Adrienne E. Smith、Nigel D. Priestley、Dennis L. Wright、Amy C. Anderson

  DOI：10.1021/jm800776a

  日期：2008.12.11

  of resistance have produced a compelling need for new therapeutic agents against this organism. Bacillus anthracis is known to be insensitive to the clinically used antifolate, trimethoprim, because of a lack of potency against the dihydrofolate reductase enzyme. Herein, we describe a novel lead series of B. anthracis dihydrofolate reductase inhibitors characterized by an extended trimethoprim-like scaffold

  炭疽芽孢杆菌是炭疽病的病原体，具有重大的生物防御危险。批准的治疗方法的严重限制和耐药性的产生已经产生了对针对这种生物的新治疗剂的迫切需求。已知炭疽芽孢杆菌对临床使用的抗叶酸甲氧苄啶不敏感，因为它对二氢叶酸还原酶缺乏效力。在此，我们描述了一种新型先导系列炭疽芽孢杆菌二氢叶酸还原酶抑制剂，其特征是扩展的甲氧苄啶样支架。最好的先导化合物的分子量仅增加 22 Da，其效力是甲氧苄啶的 82 倍。该先导化合物在 NADPH 存在下与炭疽芽孢杆菌二氢叶酸还原酶结合的 X 射线晶体结构被确定为 2.25 A 分辨率。
• HETEROCYCLIC ANALOGS OF PROPARGYL-LINKED INHIBITORS OF DIHYDROFOLATE REDUCTASE
  申请人：Anderson Amy C.

  公开号：US20120196859A1

  公开（公告）日：2012-08-02

  The compositions and methods described herein disclose the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus , fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii . These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

  本文所描述的组合物和方法揭示了设计、合成和测试作为DHFR抑制剂的化合物。这些抑制剂的基本骨架包括一个2,4-二氨基嘧啶环，带有一个丙炔基连接到另一个取代芳基、双环或杂环环上。这些DHFR抑制剂对许多不同的病原微生物具有强效和选择性作用，包括来自细菌（如炭疽芽孢杆菌和甲氧西林耐药金黄色葡萄球菌）、真菌（如光滑念珠菌、白色念珠菌和新生隐球菌）和原虫（如人类隐孢子虫和弓形虫）的DHFR酶。这些化合物和其他类似化合物也对哺乳动物酶具有强效作用，可能有用作抗癌治疗药物。
• Heterocyclic analogs of propargyl-linked inhibitors of dihydrofolate reductase
  申请人：Anderson Amy C.

  公开号：US08853228B2

  公开（公告）日：2014-10-07

  The compositions and methods described herein disclose the design, synthesis and testing of compounds that act as inhibitors of DHFR. The basic scaffold of these inhibitors includes a 2,4-diaminopyrimidine ring with a propargyl linker to another substituted aryl, bicyclo or heteroaryl ring. These DHFR inhibitors are potent and selective for many different pathogenic organisms, including the DHFR enzyme from bacteria such as Bacillus anthracis and methicillin-resistant Staphylococcus aureus, fungi such as Candida glabrata, Candida albicans and Cryptococcus neoformans and protozoa such as Cryptosporidium hominis and Toxoplasma gondii. These compounds and other similar compounds are also potent against the mammalian enzyme and may be useful as anti-cancer therapeutics.

  本文所述的组合物和方法揭示了设计、合成和测试作为DHFR抑制剂的化合物。这些抑制剂的基本支架包括一个2,4-二氨基嘧啶环，带有一个丙炔基连接到另一个取代芳基、双环或杂环环上。这些DHFR抑制剂对许多不同的致病微生物具有强效和选择性，包括来自细菌如炭疽芽孢杆菌和耐甲氧西林金黄色葡萄球菌的DHFR酶，真菌如光滑念珠菌，白色念珠菌和新型隐球菌和原虫如人类隐孢子虫和弓形虫的DHFR酶。这些化合物和其他类似化合物也对哺乳动物酶具有强效作用，可能有用作抗癌治疗药物。