thiazole-2-carbaldehyde oxime | 13838-77-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: thiazole-2-carbaldehyde oxime
• 英文别名: N-(1,3-thiazol-2-ylmethylidene)hydroxylamine
• CAS: 13838-77-2
• 化学式: C₄H₄N₂OS
• 分子量: 128.155
• InChiKey: ZOGBUYDVIGIHTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  thiazole-2-carbaldehyde oxime 在 三乙胺 、 三氟乙酸酐 作用下， 以 1,4-二氧六环 为溶剂， 生成 2-氰基噻唑
  参考文献：
  名称：

  Ethionamide Boosters. 2. Combining Bioisosteric Replacement and Structure-Based Drug Design To Solve Pharmacokinetic Issues in a Series of Potent 1,2,4-Oxadiazole EthR Inhibitors

  摘要：

  Mycobacterial transcriptional repressor EthR controls the expression of EthA, the bacterial monooxygenase activating ethionamide, and is thus largely responsible for the low sensitivity of the human pathogen Mycobacterium tuberculosis to this antibiotic. We recently reported structure-activity relationships of a series of 1,2,4-oxadiazole EthR inhibitors leading to the discovery of potent ethionamide boosters. Despite high metabolic stability, pharmacokinetic evaluation revealed poor mice exposure; therefore, a second phase of optimization was required. Herein a structure-property relationship study is reported according to the replacement of the two aromatic heterocycles: 2-thienyl and 1,2,4-oxadiazolyl moieties. This work was done using a combination of structure-based drug design and in vitro/ex vivo evaluations of ethionamide boosters on the targeted protein EthR and on the human pathogen Mycobacterium tuberculosis. Thanks to this process, we identified compound 42 (BDM41906), which displays improved efficacy in addition to high exposure to mice after oral administration.

  DOI：

  10.1021/jm200825u
• 作为产物：
  描述：

  2-醛基噻唑 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 0.67h， 以79%的产率得到thiazole-2-carbaldehyde oxime
  参考文献：
  名称：

  A New Convenient Preparation of 2-, 4-, and 5- Thiazolecarboxaldehydes and Their Conversion into the Corresponding CarbonitrileN-Oxides: Synthesis of 3-Thiazolylisoxazoles and 3-Thiazolylisoxazolines

  摘要：

  标题醛类化合物通过淬灭2-锂噻唑、4-锂-和5-锂-2-三甲基硅基噻唑与N-甲酰吗啉来制备，产率较高。在后两种情况下，随后进行脱硅化处理。这些醛类化合物通过其肟和羟肟酰氯转化为氰化物，与烯烃和乙炔二极亲电试剂反应，以中等至良好产率得到3-噻唑基异恶唑啉和3-噻唑基异恶唑。

  DOI：

  10.1055/s-1987-28146

文献信息

• Thiazole benzamide derivatives and pharmaceutical compositions for inhibiting cell proliferation, and methods for their use
  申请人：——

  公开号：US20030225147A1

  公开（公告）日：2003-12-04

  Aminothiazole compounds with mono-/di-substituted benzamide are represented by the Formula (I), and their pharmaceutically acceptable salts, pharmaceutically acceptable prodrugs, pharmaceutically active metabolites, and pharmaceutically acceptable salts of said metabolites are described. 1 These agents modulate and/or inhibit the cell proliferation and activity of protein kinases and are useful as pharmaceuticals for treating malignancies and other disorders.

  氨基噻唑化合物与单取代/双取代苯甲酰胺的结构由式(I)表示，并描述了它们的药学上可接受的盐、药学上可接受的前药、药学上活性代谢物以及所述代谢物的药学上可接受的盐。 这些药物调节和/或抑制细胞增殖和蛋白激酶活性，并可用作治疗恶性肿瘤和其他疾病的药物。
• A New Convenient Preparation of 2-, 4-, and 5- Thiazolecarboxaldehydes and Their Conversion into the Corresponding Carbonitrile<i>N</i>-Oxides: Synthesis of 3-Thiazolylisoxazoles and 3-Thiazolylisoxazolines
  作者：Alessandro Dondoni、Giancarlo Fantin、Marco Fogagnolo、Alessandro Medici、Paola Pedrini

  DOI：10.1055/s-1987-28146

  日期：——

  The title aldehydes are prepared in high Yieids by quenching 2-lithiothiazole, 4-litho-, and 5-litho-2-trimethylsilylthiazole with N-formylmorpholine followed by protodesilylation in the latter two cases. The aldehydes are transformed through their oximes and hydroxamoyl chlorides into nitrile oxides which react with alkene and acetylene dipolarophiles to give 3-thiazolylisoxazolines and 3-thiazolylisoxazoles in moderate to good yields

  标题醛类化合物通过淬灭2-锂噻唑、4-锂-和5-锂-2-三甲基硅基噻唑与N-甲酰吗啉来制备，产率较高。在后两种情况下，随后进行脱硅化处理。这些醛类化合物通过其肟和羟肟酰氯转化为氰化物，与烯烃和乙炔二极亲电试剂反应，以中等至良好产率得到3-噻唑基异恶唑啉和3-噻唑基异恶唑。
• Cyclic quaternary ammonium salts. Part VI. Synthesis of thiazolo-[3,2-a]pyrazin-5-ium salts
  作者：J. Adamson、E. C. Campbell、E. E. Glover

  DOI：10.1039/j39690002270

  日期：——

  The synthesis of the 2-oxides of thiazolo[3,2-a]pyrazinum salts (IV) and their deoxygenation to the title compounds (V) is described. An alternative route to the title compounds by intramolecular cyclisation of the anils formed between 2-acylthiazoles and aminoacetaldehyde dimethylacetal is also described.

  描述了噻唑并[3,2- a ]吡嗪鎓盐（IV）的2-氧化物的合成及其脱氧为标题化合物（V）。还描述了通过分子内环化2-酰基噻唑和氨基乙醛二甲基乙缩醛之间形成的苯胺制得标题化合物的另一种途径。
• Development of Glucose Regulated Protein 94-Selective Inhibitors Based on the BnIm and Radamide Scaffold
  作者：Vincent M. Crowley、Anuj Khandelwal、Sanket Mishra、Andrew R. Stothert、Dustin J. E. Huard、Jinbo Zhao、Aaron Muth、Adam S. Duerfeldt、James L. Kizziah、Raquel L. Lieberman、Chad A. Dickey、Brian S. J. Blagg

  DOI：10.1021/acs.jmedchem.6b00085

  日期：2016.4.14

  that was used to design isoform-selective inhibitors. Incorporation of a cis-amide bioisostere into the radamide scaffold led to development of the original Grp94-selective inhibitor, BnIm. Structure–activity relationship studies have now been performed on the aryl side chain of BnIm, which resulted in improved analogues that exhibit better potency and selectivity for Grp94. These analogues also manifest

  葡萄糖调节蛋白94（Grp94）是分子伴侣蛋白的热休克蛋白90 kDa（Hsp90）家族的内质网居民。Grp94与许多参与细胞黏附和信号传导的蛋白质相关，包括整联蛋白，Toll样受体，免疫球蛋白和突变型myocilin。Grp94被认为是包括青光眼，癌症转移和多发性骨髓瘤在内的多个治疗领域的靶标。虽然与其他Hsp90同工型具有85％的相同性，但Grp94的N末端ATP结合位点具有一个独特的疏水性口袋，该口袋用于设计同工型选择性抑制剂。合并顺式-酰胺生物甾体进入radamide支架导致了最初的Grp94选择性抑制剂BnIm的开发。现在已经对BnIm的芳基侧链进行了结构-活性关系研究，从而得到了改进的类似物，对Grp94表现出了更好的效价和选择性。与BnIm相比，这些类似物在转移模型中还表现出优异的抗迁移活性，并且在青光眼模型中还表现出增强的突变型肌球蛋白降解。
• Alkylation of Camphor and Pinanone Imines of 2-(Aminomethyl)thiazole. Enantioselective Synthesis of 2-(1-Aminoalkyl)thiazoles
  作者：Alessandro Dondoni、Francisco L. Merchan、Pedro Merino、Isabel Rojo、Tomas Tejero

  DOI：10.1055/s-1996-4259

  日期：1996.5

  A method is described for the enantioselective synthesis of 2-(1-aminoalkyl)thiazoles 6 via stereoselective alkylation of the carbanions of (+)-(R)-camphor and (-)-(1S, 2S 5S)-2-hydroxypinan-3-one-imines 2 and 3 derived from 2-(aminomethyl)thiazole (2-AMT, 1). Compounds 6 serve as α-amino aldehyde precursors via thiazolyl-to-formyl conversion.

  描述了一种通过对(+)-(R)-樟脑和(-)-(1S, 2S 5S)-2-羟基匹那酮亚胺（由2-(氨基甲基)噻唑（2-AMT, 1）衍生）进行立体选择性的烷基化，来实现2-(1-氨基烷基)噻唑化合物6的立体选择性合成的方法。化合物6可作为α-氨基醛前体，通过噻唑基转化为甲醛。