2-(Dimethylamino)-5-methyl-1,3-thiazole | 52963-36-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-(Dimethylamino)-5-methyl-1,3-thiazole
• 英文别名: dimethyl-(5-methylthiazol-2-yl)amine；dimethyl-(5-methyl-thiazol-2-yl)-amine；NoName_3479；N,N,5-trimethyl-1,3-thiazol-2-amine
• CAS: 52963-36-7
• 化学式: C₆H₁₀N₂S
• 分子量: 142.225
• InChiKey: PJAOORCTPZQZPX-UHFFFAOYSA-N

物化性质

• 沸点：
  197.6±33.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(Dimethylamino)-5-methyl-1,3-thiazole 、 四氰基乙烯 以 二氯甲烷 为溶剂， 反应 2.0h， 以25%的产率得到2-(Dimethylamino)-5-methyl-1,3-thiazolium 1,1,2,3,3-pentacyanopropenide
  参考文献：
  名称：

  Functionalization of thiazoles. Selectivity in the reactions of 2-(dimethylamino)-1,3-thiazoles with electrophiles: formation of Michael-type adducts and thiazolium salts

  摘要：

  DOI：

  10.1021/jo00326a039
• 作为产物：
  描述：

  dimethyl-(5-methylene-4,5-dihydro-thiazol-2-yl)-amine 以 xylene 为溶剂， 反应 4.0h， 生成 2-(Dimethylamino)-5-methyl-1,3-thiazole
  参考文献：
  名称：

  Eloy; Deryckere, Chimica therapeutica, 1973, vol. 8, # 4, p. 437 - 446

  摘要：

  DOI：
• 作为试剂：
  描述：

  Moore's ketene 在 2-(Dimethylamino)-5-methyl-1,3-thiazole 、 三乙胺 作用下， 生成 1,3-di-tert-butyl-1,3-dicyanoallene
  参考文献：
  名称：

  Cycloadditions with heterocycles. Reactions of tert-butylcyanoketene with 2-(dimethylamino)thiazoles

  摘要：

  DOI：

  10.1021/jo01292a013

文献信息

• [EN] PROTEOLYSIS TARGETING CHIMERIC (PROTAC) COMPOUND WITH E3 UBIQUITIN LIGASE BINDING ACTIVITY AND TARGETING ALPHA-SYNUCLEIN PROTEIN FOR TREATING NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉ CHIMÈRE CIBLANT LA PROTÉOLYSE (PROTAC) AYANT UNE ACTIVITÉ DE LIAISON À L'UBIQUITINE LIGASE E3 ET CIBLANT UNE PROTÉINE ALPHA-SYNUCLÉINE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：ARVINAS OPERATIONS INC

  公开号：WO2020041331A1

  公开（公告）日：2020-02-27

  The present disclosure relates to bifunctional compounds, which find utility as modulators of alpha-synuclein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/ inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure. Such diseases or disorders are alpha-synucleinopathies or neurodegenerative diseases associated with alpha-synuclein accumulation and aggregation, such as e.g. Parkinson Disease, Alzheimer's Disease, dementia, dementia with Lewy bodies or multiple system atrophy, in particular Parkinson's Disease.

  本公开涉及双功能化合物，其作为α-突触核蛋白（目标蛋白）的调节剂具有实用性。具体而言，本公开涉及包含一端为Von Hippel-Lindau、cereblon、凋亡抑制蛋白或鼠双分子同源物2配体的双功能化合物，该配体与相应的E3泛素连接酶结合，另一端为与目标蛋白结合的基团，使得目标蛋白靠近泛素连接酶以促使目标蛋白的降解（和抑制）。本公开展示了与目标蛋白的降解/抑制相关的广泛药理活性范围。本公开的化合物和组合物用于治疗或预防由目标蛋白聚集或积累导致的疾病或紊乱。这些疾病或紊乱是与α-突触核蛋白积累和聚集相关的α-突触核蛋白病或神经退行性疾病，例如帕金森病、阿尔茨海默病、痴呆症、带有Lewy小体的痴呆症或多系统萎缩，特别是帕金森病。
• Synthesis of Unexpected Bifunctionalized Thiazoles by Nucleophilic Attack on Allenyl Isothiocyanate
  作者：Baker Jawabrah Al-Hourani、Frank Richter、Kai Vrobel、Klaus Banert、Marcus Korb、Tobias Rüffer、Bernhard Walfort、Heinrich Lang

  DOI：10.1002/ejoc.201301851

  日期：2014.5

  reactivity is also seen with N-aminophthalimide. In the presence of azide salt, hydrazoic acid, or N,N-disubstituted hydroxylamines, however, allenyl isothiocyanate is converted into bifunctionalized thiazoles. We explain the formation of these products by nucleophilic addition at the isothiocyanato moiety followed by ring closure and an N–N or N–O cleavage reaction to generate short-lived 2-imino-5-methylidenethiazole

  用各种亲核试剂处理异硫氰酸丙二烯酯会产生在 2 位具有官能团的 5-甲基噻唑。N-氨基邻苯二甲酰亚胺也观察到相同的反应模式。然而，在叠氮化物盐、偶氮酸或 N,N-二取代羟胺的存在下，异硫氰酸烯丙酯被转化为双官能化的噻唑。我们通过在异硫氰酸基部分亲核加成，然后闭环和 N-N 或 N-O 裂解反应来生成短寿命的 2-imino-5-methylidenethiazole 或 5-methylidenethiazol-2-one 来解释这些产物的形成。这些中间体通过加成反应被捕获以得到最终的杂环化合物。在 N,N-二取代羟胺的情况下，
• METHOD FOR PRODUCING CYANOACETIC ACID, METHOD FOR PRODUCING CYANOACETIC ACID DERIVATIVE AND METHOD FOR PRODUCING METAL CONTAINING COMPOUND
  申请人：IKEMIZU Dai

  公开号：US20130253213A1

  公开（公告）日：2013-09-26

  Provided is a method for producing cyanoacetic acid in a hydrolysis reaction of a predetermined cyanoacetate in the presence of an acid catalyst. Further, are provided methods for producing a cyanoacetic acid derivative and a metal containing compound by using the produced cyanoacetic acid as a staring material. Herein, the method for producing cyanoacetic acid enables the content of a malonic acid byproduct generated in the hydrolysis reaction to be greatly lowered, allowing the produced cyanoacetic acid to be used as a starting material without any purification treatments. Those advantageous effects result in the great improvement in the purity and yields of the cyanoacetic acid derivative and the metal containing compound produced by said cyanoacetic acid. Accordingly, the above mentioned methods make it possible to produce cyanoacetic acid, the cyanoacetic acid derivative and the metal containing compound, as excellent in the productivity and economical efficiency.

  提供了一种在酸催化剂存在下，通过水解预定的氰乙酸盐生成氰乙酸的方法。此外，提供了利用生成的氰乙酸作为起始物质来生产氰乙酸衍生物和含金属化合物的方法。在这种生产氰乙酸的方法中，使得在水解反应中生成的丙二酸副产物的含量大大降低，使得生成的氰乙酸可以作为起始物质而无需任何纯化处理。这些有利效果导致了通过该氰乙酸生成的氰乙酸衍生物和含金属化合物的纯度和产量显著提高。因此，上述方法使得能够以高生产率和经济效益生产氰乙酸、氰乙酸衍生物和含金属化合物。
• SPIRO-OXINDOLE COMPOUNDS AND THEIR USE AS THERAPEUTIC AGENTS
  申请人：Chafeev Mikhail

  公开号：US20100137299A1

  公开（公告）日：2010-06-03

  This invention is directed to spiro-oxindole compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

  本发明涉及螺环氧吲哚化合物，包括其立体异构体、对映异构体、互变异构体或其混合物；或其药学上可接受的盐、溶剂化合物或前药，用于治疗和/或预防钠通道介导的疾病或症状，例如疼痛。
• SPIRO-OXINDOLE COMPOUNDS AND THEIR USES AS THERAPEUTIC AGENTS
  申请人：Chafeev Mikhail

  公开号：US20120295897A1

  公开（公告）日：2012-11-22

  This invention is directed to spiro-oxindole compounds, as stereoisomers, enantiomers, tautomers thereof or mixtures thereof; or pharmaceutically acceptable salts, solvates or prodrugs thereof, for the treatment and/or prevention of sodium channel-mediated diseases or conditions, such as pain.

  本发明涉及螺环氧吲哚化合物，包括立体异构体、对映体、互变异构体或其混合物；或其药学上可接受的盐、溶剂合物或前药，用于治疗和/或预防钠通道介导的疾病或病症，例如疼痛。