[4-amino-2-(methylthio)thiazole-5-yl](phenyl)methanone | 39736-27-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [4-amino-2-(methylthio)thiazole-5-yl](phenyl)methanone
• 英文别名: (4-amino-2-(methylthio)thiazol-5-yl)(phenyl)methanone；4-amino-5-benzoyl-2-methylthio-thiazole；4-amino-5-benzoyl-2-methylthiothiazole；(4-amino-2-methylsulfanyl-thiazol-5-yl)-phenyl-methanone；[4-amino-2-(methylthio)thiazole-5-yl] (phenyl)methanone；[4-Amino-2-(methylsulfanyl)-1,3-thiazol-5-yl](phenyl)methanone；(4-amino-2-methylsulfanyl-1,3-thiazol-5-yl)-phenylmethanone
• CAS: 39736-27-1
• 化学式: C₁₁H₁₀N₂OS₂
• 分子量: 250.345
• InChiKey: QVPDSWIYSVKEKP-UHFFFAOYSA-N

物化性质

• 熔点：
  149-151 °C(Solv: ethanol (64-17-5))
• 沸点：
  482.1±55.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [4-amino-2-(methylthio)thiazole-5-yl](phenyl)methanone 在 亚硝酸特丁酯 、 copper dichloride 作用下， 以 乙腈 为溶剂， 以31%的产率得到(4-chloro-2-(methylsulfanyl)-1,3-thiazol-5-yl)(phenyl)methanone
  参考文献：
  名称：

  4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K+-ATPase and Ras oncogene activity in cancer cells

  摘要：

  The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12a) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12b) displayed similar to 10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na+/K+-ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.046
• 作为产物：
  描述：

  [Methylsulfanyl(phenacylsulfanyl)methylidene]cyanamide 在 potassium carbonate 作用下， 反应 1.0h， 生成 [4-amino-2-(methylthio)thiazole-5-yl](phenyl)methanone
  参考文献：
  名称：

  4-Bromo-2-(piperidin-1-yl)thiazol-5-yl-phenyl methanone (12b) inhibits Na+/K+-ATPase and Ras oncogene activity in cancer cells

  摘要：

  The in vitro growth inhibitory activity of 26 thiazoles (including 4-halogeno-2,5-disubtituted-1,3-thiazoles) and 5 thienothiazoles was assessed on a panel of 6 human cancer cell lines, including glioma cell lines. (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12a) and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone (12b) displayed similar to 10 times greater in vitro growth inhibitory activity than perillyl alcohol (POH), which therapeutically benefits glioma patients through the inhibition of both alpha-1 Na+/K+-ATPase (NAK) and Ras oncogene activity. The in vitro cytostatic activities (as revealed by quantitative videomicroscopy) displayed by 12a and 12b were independent of the intrinsic resistance to pro-apoptotic stimuli associated with cancer cells. Compounds 12a and 12b displayed relatively similar inhibitory activities on purified guinea pig brain preparations that mainly express NAK alpha-2 and alpha-3 subunits, whereas only compound 12b was efficacious against purified guinea pig kidney preparations that mainly express the NAK alpha-1 subunit, which is also expressed in gliomas, melanomas and non-small-cell lung cancers NSCLCs. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.046

文献信息

• Beiträge zum reaktionsverhalten von derivaten der imidodithiokohlensäure—I
  作者：W. Walek、M. Pallas、M. Augustin

  DOI：10.1016/s0040-4020(01)93783-4

  日期：1976.1

  The reaction of potassium-alkyl-cyanoimidodithiocarbonate 1 with α-CH-acid halo compounds to 4-aminothiazoles 3, with monochloramine to 3-amino-1,2,4-thiadiazoles 5, and with α-halocarboxylic acid anilides to 4-thiazolidinones derivatives 12 is described. Characteristics of mass- and IR-spectra of the synthesized compounds are discussed.

  烷基烷基氰基氨基二硫代碳酸钾1与α-CH-酸卤代化合物反应成4-氨基噻唑3，一氯胺反应生成3-氨基-1,2,4-噻二唑5，与α-卤代羧酸酐反应成4-噻唑烷酮描述了导数12。讨论了合成化合物的质谱和红外光谱特征。
• NBS-mediated sequential one-pot synthesis of multifunctionalized thiazoles and thiophenes from 1,3-dicarbonyl compounds and mercaptonitrile salts
  作者：Laichun Luo、Lanlan Meng、Qi Sun、Zemei Ge、Runtao Li

  DOI：10.1016/j.tetlet.2013.11.014

  日期：2014.1

  A NBS-mediated sequential one-pot synthesis of multifunctionalized thiazoles and thiophenes from 1,3-dicarbonyl compounds and mercaptonitrile salts has been developed under mild conditions. This transformation involves sequential bromination/SN2 alkylation/Thorpe–Ziegler cyclization/regio-selective elimination of a –COR group, affording the desired products in moderate to good yields. The sequence

  由NBS介导的从1,3-二羰基化合物和硫醇腈盐开始的多官能噻唑和噻吩的顺序一锅法合成已经在温和的条件下进行。该转化涉及顺序溴化/ S N 2烷基化/索普-齐格勒环化/ -COR基团的区域选择性消除，以中等至良好的收率提供所需的产物。确定了-COR基团离去反应的顺序，并提出了可能的机制。
• [EN] NOVEL BRIDGED BICYCLOALKYL-SUBSTITUTED AMINOTHIZOLES AND THEIR METHODS OF USE<br/>[FR] NOUVEAUX AMINOTHIAZOLES À SUBSTITUTION BICYCLOALKYLE PONTÉS ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV TEMPLE

  公开号：WO2018136766A1

  公开（公告）日：2018-07-26

  The present invention includes novel bridged bicycloalkyl-substituted aminothiazole compounds useful in preventing or treating cancer in a subject in need thereof. The present invention also includes methods of preventing or treating cancer in a subject in need thereof by administering to the subject a therapeutically effective amount of a compound of the invention.

  本发明涉及一种新颖的桥联双环烷基取代的氨基噻唑化合物，用于预防或治疗需要的患者的癌症。本发明还涉及通过向患者施用本发明化合物的治疗有效量来预防或治疗需要的患者的癌症的方法。
• Identification of Metabolites of <i>N</i>-(5-Benzoyl-2-(4-(2-Methoxyphenyl)piperazin-1-yl)thiazol-4-yl)pivalamide Including CYP3A4-Mediated <i>C</i>-Demethylation in Human Liver Microsomes with High-Resolution/High-Accuracy Tandem Mass
  作者：Min Song、Doohyun Lee、Sun Kim、Jong-Sup Bae、Jaeick Lee、Young-Dae Gong、Taeho Lee、Sangkyu Lee

  DOI：10.1124/dmd.114.057570

  日期：2014.8

  KRO-105714 [ N -(5-benzoyl-2-(4-(2-methoxyphenyl)piperazin-1-yl)thiazol-4-yl)pivalamide] is a 2,4,5-trisubstituted 1,3-thiazole derivative that exerts anti–atopic dermatitis activity via robust suppression of the sphingosylphosphorylcholine receptor. This study used high-resolution/high-accuracy tandem mass spectroscopy (HRMS) and recombinant cDNA–expressed cytochrome P450 (P450) isoforms to identify the metabolic pathway and metabolites of KRO-105714 in human liver microsomes (HLMs) as therapeutic agents for inflammation. The incubation of KRO-105714 with pooled HLMs in the presence of NADPH generated four metabolites (M1–M4). The metabolites were identified using HRMS and confirmed using synthetic standards for M2 and M4. M1 and M2 were identified as monohydroxylated metabolites, and M3 and M4 were identified as O -demethyl KRO-105714 and C -demethyl KRO-105714, respectively. In the inhibition study with selective CYP3A4 inhibitors and incubation in recombinant cDNA–expressed P450 enzymes, all the metabolites of KRO-105714 were formed by CYP3A4 in HLMs. The CYP3A4-mediated formation of M4 from M2 was confirmed via incubation of M2 in HLMs. These results showed that the unusual C -demethylated metabolite M4 was generated from monohydroxyl metabolite M2 via a CYP3A4-mediated enzymatic reaction in HLMs.

  KRO-105714 [ N -(5-苯甲酰基-2-(4-(2-甲氧基苯基)哌嗪-1-基)噻唑-4-基)特戊酰胺 ] 是一种 2,4,5-三取代的 1,3-thiazole 衍生物，它通过强效抑制鞘氨醇磷酸胆碱受体而发挥抗异位性皮炎的活性。本研究利用高分辨率/高精度串联质谱（HRMS）和重组 cDNA 表达的细胞色素 P450（P450）同工酶来鉴定 KRO-105714 在人肝微粒体（HLMs）中的代谢途径和代谢产物，并将其作为治疗炎症的药物。在 NADPH 存在下，KRO-105714 与汇集的 HLMs 一起孵育会产生四种代谢物（M1-M4）。利用 HRMS 对代谢物进行了鉴定，并利用合成标准对 M2 和 M4 进行了确认。M1 和 M2 被鉴定为单羟化代谢物，M3 和 M4 分别被鉴定为 O -demethyl KRO-105714 和 C -demethyl KRO-105714。在使用选择性 CYP3A4 抑制剂和重组 cDNA 表达的 P450 酶进行抑制研究时，KRO-105714 的所有代谢物都是由 CYP3A4 在 HLMs 中形成的。通过在 HLMs 中培养 M2，证实了 CYP3A4 介导的 M4 由 M2 形成。这些结果表明，在 HLMs 中，单羟基代谢物 M2 通过 CYP3A4 介导的酶促反应生成了不常见的 C 去甲基代谢物 M4。
• Solid-Phase Synthesis of Thiazolo[4,5-<i>b</i>]pyridine Derivatives Using Friedländer Reaction
  作者：Taeho Lee、Doohyun Lee、Ill Young Lee、Young-Dae Gong

  DOI：10.1021/cc900147y

  日期：2010.1.11

  Traceless solid-phase synthesis of 2,5,6,7-tetrasubstituted thiazolo[4,5-b]pyridine derivatives is described. Thorpe-Ziegler type cyclization of solid supported cyanocarbonimidodithioate with alpha-halo ketones afforded thiazole resin, which were converted to the desired thiazolopyridine resin by the Friedlander protocol under microwave irradiation conditions. After oxidation of sulfides to sulfones

  描述了2,5,6,7-四取代的噻唑并[4,5-b]吡啶衍生物的无痕固相合成。用α-卤代酮对固体负载的氰基碳亚氨基二硫代酸酯进行Thorpe-Ziegler型环化反应，得到噻唑树脂，并通过Friedlander方案在微波辐射条件下将其转化为所需的噻唑并吡啶树脂。在将硫化物氧化为砜后，用胺进行亲核性的脱磺基取代反应可得到目标噻唑并[4,5-b]吡啶衍生物，且总收率良好。