2-氨基-N-(2-氯-6-甲基苯基)-5-噻唑酰胺 | 4720-68-7

• 物质功能分类: 医药中间体 - 原料药中间体
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并间二氧杂环戊烯类
• 中文名称: 2-氨基-N-(2-氯-6-甲基苯基)-5-噻唑酰胺
• 英文名称: 4,5-methylenedioxy-2-hydroxybenzaldehyde
• 英文别名: 6-hydroxybenzo[d][1,3]dioxole-5-carbaldehyde；2-hydroxy-4,5-methylenedioxybenzaldehyde；6-hydroxypiperonal；6-hydroxy-3,4-(methylenedioxy)benzaldehyde；6-hydroxy-2H-1,3-benzodioxole-5-carbaldehyde；6-hydroxy-1,3-benzodioxole-5-carbaldehyde
• CAS: 4720-68-7
• 化学式: C₈H₆O₄
• mdl: MFCD09864084
• 分子量: 166.133
• InChiKey: SXMMQAVECVAGBF-UHFFFAOYSA-N

物化性质

• 熔点：
  125-126 °C
• 沸点：
  296.7±40.0 °C(Predicted)
• 密度：
  1.500±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.125
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  | 室温下，保存于惰性气体中 |

反应信息

• 作为反应物：
  描述：

  2-氨基-N-(2-氯-6-甲基苯基)-5-噻唑酰胺 在 potassium cyanide 、 manganese(IV) oxide 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成 Methyl 6-(methoxymethoxy)-1,3-benzodioxole-5-carboxylate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Study of Lamellarin Derivatives

  摘要：

  Ten derivatives (3-12) of marine alkaloid lamellarin D (1) were synthesized and evaluated for cytotoxicity against a HeLa cell line in an effort to examine their structure-activity relationships. It appeared that the hydroxyl groups at positions C-8 and C-20 of 1 were important structural requirements for cytotoxic activity, while the hydroxyl group at C-14 and the two methoxy groups at C-13 and C-21 were not necessary for the activity.

  DOI：

  10.1021/np0104525
• 作为产物：
  描述：

  6-氨基苯并[1,3]二氧杂环戊烯-5-甲醛 在 硫酸 、 sodium nitrite 、 水 、 copper(II) sulfate 作用下， 以 水 为溶剂， 反应 8.0h， 以58%的产率得到2-氨基-N-(2-氯-6-甲基苯基)-5-噻唑酰胺
  参考文献：
  名称：

  Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis

  摘要：

  A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC50 = 20.74 mu M and 16.40 mu M, respectively. The intracellular amastigotes assays showed IC50 = 22.00 mu M (22) and 17.00 mu M (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.09.009

文献信息

• [EN] CHROMAN-4-ONE DERIVATIVES FOR THE TREATMENT AND PROPHYLAXIS OF HEPATITIS B VIRUS INFECTION<br/>[FR] DÉRIVÉS DE CHROMAN-4-ONE POUR LE TRAITEMENT ET LA PROPHYLAXIE D'UNE INFECTION PAR LE VIRUS DE L'HÉPATITE B
  申请人：HOFFMANN LA ROCHE

  公开号：WO2020120642A1

  公开（公告）日：2020-06-18

  The present invention provides compounds having the general formula (I) wherein R1 to R10, Gi, G2, X and m are as described herein, compositions including the compounds and methods of using the compounds for treating hepatitis B.

  本发明提供具有一般式（I）的化合物，其中R1至R10、Gi、G2、X和m如本文所述，包括这些化合物的组合物以及使用这些化合物治疗乙型肝炎的方法。
• Controllable Rh(III)-Catalyzed Annulation between Salicylaldehydes and Diazo Compounds: Divergent Synthesis of Chromones and Benzofurans
  作者：Peng Sun、Shang Gao、Chi Yang、Songjin Guo、Aijun Lin、Hequan Yao

  DOI：10.1021/acs.orglett.6b03355

  日期：2016.12.16

  A Rh(III)-catalyzed annulation between salicylaldehydes and diazo compounds with controllable chemoselectivity is described. AgNTf2 favored benzofurans via a tandem C–H activation/decarbonylation/annulation process, while AcOH led to chromones through a C–H activation/annulation pathway. The reaction exhibited good functional group tolerance and scalability. Moreover, only a single regioisomer of benzofuran

  描述了Rh（III）催化的水杨醛和重氮化合物之间具有可控的化学选择性的环化反应。AgNTf 2通过串联的C–H活化/脱羰/环化过程有利于苯并呋喃，而AcOH通过C–H活化/环化途径生成色酮。该反应表现出良好的官能团耐受性和可扩展性。此外，由于原位脱羰取向作用，仅获得了单一的苯并呋喃的区域异构体。
• Exploring tertiary enamides as versatile synthons in organic synthesis
  作者：Mei-Xiang Wang

  DOI：10.1039/c4cc10327k

  日期：——

  Tertiary enamides have long been thought of as stable and marginally valuable enamine variants in synthesis. This notion has been challenged, however, in recent years. Enabling the regulation of the cross-conjugation system of the tertiary enamides has been successfully shown to enhance delocalization of the nitrogen lone-pair electrons into a carbon-carbon double, thereby reinvigorating the enaminic

  长期以来一直认为叔酰胺是合成中稳定的和边际上有价值的烯胺变体。但是，近年来，这一概念受到了挑战。已成功地显示出使叔酰胺的交叉缀合系统的调节能够增强氮孤对电子的离域化为碳-碳双键，从而使叔酰胺的烯胺反应性恢复活力。在本文中，我总结了叔酰胺类化合物亲核反应探索的最新进展及其在天然产物和具有生物学和药学意义的杂环化合物的合成中的应用，主要侧重于我们自己的工作。
• Novel thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US20040009995A1

  公开（公告）日：2004-01-15

  Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I 1 or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R 3 , R 4 and R 7 are defined in the specification, Z is SO or SO 2 , and Ar is an aromatic or heteroaromatic group as defined herein.

  揭示了一种治疗急性或慢性疾病症状的方法，该方法通过补体级联的经典途径介导，包括向需要此类治疗的哺乳动物施用公式I的化合物的治疗有效量或其溶剂化合物、水合物或药用可接受盐；其中在规范中定义了R1、R2、R3、R4和R7，Z为SO或SO2，Ar为本文中定义的芳香族或杂环芳基。
• Ethyl Cinnamate Derivatives as Promising High-Efficient Acaricides against &lt;i&gt;Psoroptes cuniculi&lt;/i&gt;: Synthesis, Bioactivity and Structure–Activity Relationship
  作者：Bingyu Zhang、Chao Lv、Weibo Li、Zhiming Cui、Dongdong Chen、Fangjun Cao、Fang Miao、Le Zhou

  DOI：10.1248/cpb.c14-00765

  日期：——

  This paper reported the synthesis, structure–activity relationship (SAR) and acaricidal activity in vitro against Psoroptes cuniculi, a mange mite, of 25 ethyl cinnamate derivatives. All target compounds were synthesized and elucidated by means of MS, 1H- and 13C-NMR analysis. The results showed that 24 out of 25 tested compounds at 1.0 mg/mL demonstrated acaricidal activity in varying degrees. Among them, 6, 15, 26, 27 and 30 showed significant activity with median lethal concentration values (LC50) of 89.3, 119.0, 39.2, 29.8 and 41.2 µg/mL, respectively, which were 2.1- to 8.3-fold the activity of ivermectin (LC50=247.4 µg/mL), a standard drug in the treatment of Psoroptes cuniculi. Compared with ivermectin, with a median lethal time value (LT50) of 8.9 h, 27 and 30 showed smaller LT50 values of 7.9 and 1.3 h, respectively, whereas 6, 15 and 26 showed slightly larger LT50 values of 10.6, 11.0 and 10.4 h at 4.5 µmol/mL. SARs showed that the presence of o-NO2 or m-NO2 on the benzene ring significantly improved the activity, whereas the introduction of a hydroxy, methoxy, acetoxy, methylenedioxy, bromo or chloro group reduced the activity. (E)-Cinnamates were more effective than their (Z)-isomer. Nevertheless, the carbon–carbon double bond in the acrylic ester moiety was proven not to be essential to improve the activity of cinnamic acid esters. Thus, the results strongly indicate that cinnamate derivatives, especially their dihydro derivatives, should be promising candidates or lead compounds for the development of novel acaricides for the effective control of animal or human acariasis.

  本研究报道了25种肉桂酸乙酯衍生物的合成、构效关系及其对兔疥螨的杀螨活性。所有目标化合物通过MS、1H-和13C-NMR进行了表征。结果表明,25个化合物中有24个在1.0mg/mL浓度下表现出不同程度的杀螨活性。其中,6、15、26、27和30号化合物显示出显著的活性,半数致死浓度值(LC50)分别为89.3、119.0、39.2、29.8和41.2μg/mL,分别是伊维菌素(LC50=247.4μg/mL)的2.1-8.3倍。与伊维菌素(半数致死时间LT50为8.9h)相比,27和30号化合物的LT50值更小,分别为7.9h和1.3h,而6、15和26号化合物的LT50值稍大,分别为10.6、11.0和10.4h(4.5μmol/mL)。构效关系表明,苯环上的邻硝基或间硝基显著提高了活性,而引入羟基、甲氧基、乙酰氧基、亚甲二氧基、溴或氯则降低了活性。(E)-肉桂酸酯比其(Z)-异构体更有效。然而,丙烯酸酯部分的碳-碳双键对于提高肉桂酸酯的活性并非必需。因此,结果强烈表明,肉桂酸酯衍生物,尤其是其二氢衍生物,应该是开发新型杀螨剂以有效控制人和动物螨病的极具潜力的候选物或先导化合物。