1,3-thiazole-5-carbaldehyde oxime | 116045-57-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,3-thiazole-5-carbaldehyde oxime
• 英文别名: thiazole-5-carbaldehyde oxime；Thiazole-5-carbaldehyde oxime；N-(1,3-thiazol-5-ylmethylidene)hydroxylamine
• CAS: 116045-57-9
• 化学式: C₄H₄N₂OS
• 分子量: 128.155
• InChiKey: NYLFWCLYZJUCIW-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：

  1,3-thiazole-5-carbaldehyde oxime 在 三乙胺 、 三氟乙酸酐 作用下， 以 1,4-二氧六环 为溶剂， 以58%的产率得到5-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：

  5-噻唑甲醛 在 sodium hydroxide 、 盐酸羟胺 作用下， 以 乙醇 为溶剂， 反应 0.67h， 以85%的产率得到1,3-thiazole-5-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

• Copper-Catalyzed β-Lactam Formation Initiated by 1,3-Azaprotio Transfer of Oximes and Methyl Propiolate
  作者：Zhenjie Qi、Shaozhong Wang

  DOI：10.1021/acs.orglett.1c01937

  日期：2021.8.6

  A copper(II)-catalyzed protocol to construct trans-configured β-lactams and spirocyclic β-lactams from oximes and methyl propiolate has been developed, which features excellent substrate flexibility and diastereoselectivity (up to >99:1 dr). In situ FT-IR mechanistic experiments support that ketene species might be involved in the formation of β-lactams.

  已经开发了一种铜 (II) 催化的协议，用于从肟和丙炔酸甲酯构建反式配置的β-内酰胺和螺环 β-内酰胺，其具有出色的底物灵活性和非对映选择性（高达 >99:1 dr）。原位 FT-IR 机械实验支持乙烯酮物质可能参与 β-内酰胺的形成。
• 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。
• [EN] 1, 2, 4 - OXADIAZOLE DERIVATIVES AS ETHR INHIBITORS FOR USE IN THE TREATMENT TUBERCULOSIS<br/>[FR] COMPOSÉS PRÉSENTANT UNE ACTIVITÉ D'INHIBITION D'ETHR, UTILISATION DESDITS COMPOSÉS EN TANT QUE MÉDICAMENTS, COMPOSITION PHARMACEUTIQUE ET PRODUIT CONTENANT LESDITS COMPOSÉS
  申请人：UNIV LILLE II DROIT & SANTE

  公开号：WO2013060744A3

  公开（公告）日：2013-06-20
• 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
  作者：Marion Flipo、Matthieu Desroses、Nathalie Lecat-Guillet、Baptiste Villemagne、Nicolas Blondiaux、Florence Leroux、Catherine Piveteau、Vanessa Mathys、Marie-Pierre Flament、Juergen Siepmann、Vincent Villeret、Alexandre Wohlkönig、René Wintjens、Sameh H. Soror、Thierry Christophe、Hee Kyoung Jeon、Camille Locht、Priscille Brodin、Benoit Déprez、Alain R. Baulard、Nicolas Willand

  DOI：10.1021/jm200825u

  日期：2012.1.12

  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.
• Uncharged mono- and bisoximes: In search of a zwitterion to countermeasure organophosphorus intoxication
  作者：Lukas Gorecki、Aneta Markova、Vendula Hepnarova、Natalie Zivna、Lucie Junova、Martina Hrabinova、Jiri Janousek、Tereza Kobrlova、Lukas Prchal、Daniel Jun、Ondrej Soukup、Gabriele Horn、Franz Worek、Jan Marek、Jan Korabecny

  DOI：10.1016/j.cbi.2024.110941

  日期：2024.5

  imposes a new class of organophosphorus (OP)-inhibited cholinesterase reactivators by conceptualizing a family of asymmetric bisoximes with various reactivating scaffolds. Several novel nucleophilic warheads were investigated, putting forward 29 novel reactivating options, by evaluating their nucleophilicity and ability to directly decompose OP compounds. Adopting the so-called zwitterionic strategy, 17

  目前的研究通过概念化具有各种重新激活支架的不对称双肟家族，提出了一类新的有机磷（OP）抑制胆碱酯酶重新激活剂。研究了几种新型亲核弹头，通过评估其亲核性和直接分解OP化合物的能力，提出了29种新型重新激活选项。采用所谓的两性离子策略，发现了 17 种单肟和 9 种双肟重激活剂，重点是双功能部分方法。将化合物与临床使用的标准品和其他已知的实验突出的再激活剂进行比较。我们的结果显然支持不对称双肟作为功效和多功能性方面领先的再激活剂的概念。这些排名靠前的化合物通过再激活动力学参数进行了详细表征，并评估了潜在的中枢神经系统可用性。突出显示的分子 、 和 具有各种重新激活弹头，超过了解磷定和几种著名的不带电重新激活剂的重新激活效力。还针对 OP 抑制的丁酰胆碱酯酶检查了主要候选药物的多功能性，结果显示与现有的临床解毒剂相比，其比率要高得多。