(4-甲基呋咱-3-基)-乙酸 | 15323-69-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (4-甲基呋咱-3-基)-乙酸
• 英文名称: 2-(4-methyl-1,2,5-oxadiazol-3-yl)acetic acid
• 英文别名: (4-methyl-1,2,5-oxadiazol-3-yl)acetic acid；(4-methyl-furazan-3-yl)-acetic acid
• CAS: 15323-69-0
• 化学式: C₅H₆N₂O₃
• mdl: MFCD06010348
• 分子量: 142.114
• InChiKey: KTQDLOCXIKPNTI-UHFFFAOYSA-N

物化性质

• 熔点：
  83-84 °C
• 沸点：
  295.4±32.0 °C(Predicted)
• 密度：
  1.387±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  76.2
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  (4-甲基呋咱-3-基)-乙酸 在 五氯化磷 作用下， 反应 2.0h， 生成 (4-methyl-1,2,5-oxadiazol-3-yl)acetic acid chloride
  参考文献：
  名称：

  Esterification of 1,2,5-oxadiazolylacetic acids with polynitro alcohols

  摘要：

  4-取代(1,2,5-恶二唑-3-基)乙酸与2,2,2-三硝基和2-氟-2,2-二硝基乙醇的反应生成相应的酯，这些酯可以作为气体生成组合物的组分。

  DOI：

  10.1007/s11172-009-0303-0
• 作为产物：
  描述：

  1-(4-甲基-1,2,5-噁二唑-3-基)-1-乙酮 在 硫酸 、 sulfur 作用下， 反应 13.0h， 生成 (4-甲基呋咱-3-基)-乙酸
  参考文献：
  名称：

  Tselinskii; Mel'nikova; Zelenov, Russian Journal of Organic Chemistry, 1996, vol. 32, # 5, p. 734 - 737

  摘要：

  DOI：

文献信息

• Lithiation of five-membered heteroaromatic compounds. The methyl substituted 1,2-azoles, oxadiazoles, and thiadiazoles
  作者：R. G. Micetich

  DOI：10.1139/v70-334

  日期：1970.7.1

  The lithiation of various methyl substituted isoxazoles, isothiazoles, pyrazoles, oxadiazoles, and thiadiazoles using n-butyllithium has been studied. Three types of reactions, namely, lateral lithiation, ring cleavage, and addition of butyllithium to the ring, have been found. 3,5-Dimethylisoxazole, 3-phenyl-5-methylisoxazole, 3,4-dimethyl-1,2,5-oxadiazole, 2,5-dimethyl-1,3,4-thiadiazole, 3-phenyl-5-methyl-1,2,4-oxadiazole, and 3,5-dimethyl-1,2,4-thiadiazole all undergo lateral lithiation to give the respective acetic acids after carboxylation. 1-Methyl-3,5-disubstituted pyrazoles form the 1-lithiomethyl derivatives, while 1-phenyl-3,5-disubstituted pyrazoles are converted to the 1-ortholithiophenyl-3,5-disubstituted pyrazoles. 4-Methylisothiazole is lithiated mainly at C-5, but also suffers ring cleavage to form 1-n-butylthio-2-cyanoprop-1-ene. Heteroaromatic compounds containing an N—S bond, such as 3,4-dimeth yl-1,2,5-thiadiazole, 4-methyl-5-phenyl-1,2,3-thiadiazole, and 3,5-dimethylisothiazole, undergo nucleophilic attack at sulfur with resulting ring cleavage. 3,5-Dimethylisothiazole produces 2-n-butylthiopent-2-en-4-one. 3-Methyl-5-phenyl-1,2,4-oxadiazole gave 3-methyl-5-phenyl-5-n-butyl-1,2,4-dihydroöxadiazole by addition to the azomethine bond. The results of these lithiations are discussed. 3-Methyl-5-lithiomethylisoxazole was converted to various derivatives. Nuclear magnetic resonance spectral analysis was used to establish the identity of the products.

  各种甲基取代异噁唑、异硫唑、吡唑、噁二唑和噻二唑的锂化反应已经被研究。发现了三种类型的反应，即侧链锂化、环裂解和丁基锂加入环中。3,5-二甲基异噁唑、3-苯基-5-甲基异噁唑、3,4-二甲基-1,2,5-噁二唑、2,5-二甲基-1,3,4-噻二唑、3-苯基-5-甲基-1,2,4-噁二唑和3,5-二甲基-1,2,4-噻二唑都经历侧链锂化，在羧化后生成相应的乙酸。1-甲基-3,5-二取代吡唑形成1-锂甲基衍生物，而1-苯基-3,5-二取代吡唑转化为1-邻锂苯基-3,5-二取代吡唑。4-甲基异硫唑主要在C-5处发生锂化，但也发生环裂解形成1-正丁硫基-2-氰基丙-1-烯。含有N—S键的杂环化合物，如3,4-二甲基-1,2,5-噻二唑、4-甲基-5-苯基-1,2,3-噻二唑和3,5-二甲基异硫唑，在硫原子上发生亲核攻击，导致环裂解。3,5-二甲基异硫唑产生2-正丁硫代戊-2-烯-4-酮。3-甲基-5-苯基-1,2,4-噁二唑通过加成到偶氮亚胺键生成3-甲基-5-苯基-5-正丁基-1,2,4-二氢噁二唑。讨论了这些锂化的结果。3-甲基-5-锂甲基异噁唑被转化为各种衍生物。核磁共振光谱分析用于确定产物的身份。
• ACYLAMINO-SUBSTITUTED FUSED CYCLOPENTANECARBOXYLIC ACID DERIVATIVES AND THEIR USE AS PHARMACEUTICALS
  申请人：SCHAEFER Matthias

  公开号：US20110152290A1

  公开（公告）日：2011-06-23

  The present invention relates to compounds of the formula I, wherein A, Y, Z, R 3 to R 6 , R 20 to R 22 and R 50 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. Specifically, they are inhibitors of the endothelial differentiation gene receptor 2 (Edg-2, EDG2), which is activated by lysophosphatidic acid (LPA) and is also termed as LPA 1 receptor, and are useful for the treatment of diseases such as atherosclerosis, myocardial infarction and heart failure, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

  本发明涉及式I的化合物，其中A、Y、Z、R3至R6、R20至R22和R50具有所述权利要求中指示的含义，这些化合物是有价值的药物活性化合物。具体来说，它们是内皮分化基因受体2（Edg-2，EDG2）的抑制剂，该受体被溶血磷脂酸（LPA）激活，也称为LPA1受体，可用于治疗动脉粥样硬化、心肌梗塞和心力衰竭等疾病。本发明还涉及制备式I化合物的方法、它们的用途以及包含它们的药物组合物。
• Acylamino-substituted fused cyclopentanecarboxylic acid derivatives and their use as pharmaceuticals
  申请人：Schaefer Matthias

  公开号：US08362073B2

  公开（公告）日：2013-01-29

  The present invention relates to compounds of the formula I, wherein A, Y, Z, R3 to R6, R20 to R22 and R50 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. Specifically, they are inhibitors of the endothelial differentiation gene receptor 2 (Edg-2, EDG2), which is activated by lysophosphatidic acid (LPA) and is also termed as LPA1 receptor, and are useful for the treatment of diseases such as atherosclerosis, myocardial infarction and heart failure, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

  本发明涉及公式I的化合物，其中A，Y，Z，R3至R6，R20至R22和R50具有所述索引中指示的含义，它们是有价值的药物活性化合物。具体来说，它们是内皮分化基因受体2（Edg-2，EDG2）的抑制剂，该受体被溶血磷脂酸（LPA）激活，也称为LPA1受体，对于治疗动脉粥样硬化、心肌梗死和心力衰竭等疾病有用。本发明还涉及制备公式I化合物的方法、它们的使用以及包含它们的药物组合物。
• Highly Selective Sub-Nanomolar Cathepsin S Inhibitors by Merging Fragment Binders with Nitrile Inhibitors
  作者：Markus Schade、Beatrix Merla、Bernhard Lesch、Markus Wagener、Simone Timmermanns、Katrien Pletinckx、Torsten Hertrampf

  DOI：10.1021/acs.jmedchem.0c00949

  日期：2020.10.22

  Pharmacological inhibition of cathepsin S (CatS) allows for a specific modulation of the adaptive immune system and many major diseases. Here, we used NMR fragment screening and crystal structure-aided merging to synthesize novel, highly selective CatS inhibitors with picomolar enzymatic Ki values and nanomolar functional activity in human Raji cells. Noncovalent fragment hits revealed binding hotspots, while the covalent inhibitor structure-activity relationship enabled efficient potency optimization.
• Antibacterial activity of 6-(5-membered heteroarylacetamido)penicillanic acids
  作者：Ronald G. Micetich、Rintje Raap、John Howard、Imre Pushkas

  DOI：10.1021/jm00273a033

  日期：1972.3