N-羟基-3-[1-(苯基硫代)甲基-1H-1,2,3-三氮唑-4-基]苯甲酰胺 | 1316652-41-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: N-羟基-3-[1-(苯基硫代)甲基-1H-1,2,3-三氮唑-4-基]苯甲酰胺
• 英文名称: NCC-149
• 英文别名: N-hydroxy-3-[1-(phenylthio)methyl-1H-1,2,3-triazol-4-yl]benzamide；N-Hydroxy-3-[1-(phenylthio)methyl-1H-1,2,3-triazol-4-yl]benzamide；N-hydroxy-3-[1-(phenylsulfanylmethyl)triazol-4-yl]benzamide
• CAS: 1316652-41-1
• 化学式: C₁₆H₁₄N₄O₂S
• 分子量: 326.379
• InChiKey: DORPIZJGSLWDIY-UHFFFAOYSA-N

物化性质

• 熔点：
  153 °C(dec.)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 储存条件：
  温度控制在0-10℃范围内，并请避免加热。

制备方法与用途

NCC-149 是一种选择性 HDAC8 抑制剂，适用于神经分化的研究。

反应信息

• 作为产物：
  描述：

  甲基苯基亚砜 在 三乙烯二胺 、 copper(l) iodide 、 二(对硝基苯基)叠氮膦酸酯 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 5.0h， 生成 N-羟基-3-[1-(苯基硫代)甲基-1H-1,2,3-三氮唑-4-基]苯甲酰胺
  参考文献：
  名称：

  双（对-硝基苯基）叠氮化磷作为叠氮化试剂的Pummerer重排：叠氮基甲基硫化物的新型合成

  摘要：

  提出了一种以双（对硝基苯基）叠氮化磷（p -NO 2 DPPA）为叠氮化试剂，通过Pummerer重排合成叠氮叠氮化物的新方法。将各种甲基亚砜转化为相应的叠氮基甲基硫化物。重要的是，该反应能够在不使用有毒或易爆的叠氮化物源的情况下制备叠氮基甲基硫化物。

  DOI：

  10.1016/j.tetlet.2017.08.065

文献信息

• Rapid Discovery of Highly Potent and Selective Inhibitors of Histone Deacetylase 8 Using Click Chemistry to Generate Candidate Libraries
  作者：Takayoshi Suzuki、Yosuke Ota、Masaki Ri、Masashige Bando、Aogu Gotoh、Yukihiro Itoh、Hiroki Tsumoto、Prima R. Tatum、Tamio Mizukami、Hidehiko Nakagawa、Shinsuke Iida、Ryuzo Ueda、Katsuhiko Shirahige、Naoki Miyata

  DOI：10.1021/jm300837y

  日期：2012.11.26

  μM), which was more potent than PCI-34058 (6) (IC50 = 0.31 μM), a known HDAC8 inhibitor. Molecular modeling suggested that the phenylthiomethyl group of C149 binds to a unique hydrophobic pocket of HDAC8, and the orientation of the phenylthiomethyl and hydroxamate moieties (fixed by the triazole moiety) is important for the potency and selectivity. The inhibitors caused selective acetylation of cohesin

  为了找到HDAC8选择性抑制剂，我们设计了一个HDAC抑制剂候选物库，每个候选物均包含一个与活性位点锌离子配位的锌结合基团，并通过三唑部分连接至一个与帽沿边缘上的残基相互作用的加帽结构活动站点。这些化合物通过点击化学合成。筛选鉴定出的HDAC8选择性抑制剂包括C149（IC 50 = 0.070μM），其比已知的HDAC8抑制剂PCI-34058（6）（IC 50 = 0.31μM）更有效。分子建模表明，C149的苯硫基甲基结合到HDAC8的独特疏水口袋，并且苯硫甲基和异羟肟酸酯部分（由三唑部分固定）的方向对于效价和选择性很重要。抑制剂引起细胞内黏附素的选择性乙酰化，并对T细胞淋巴瘤和神经母细胞瘤细胞产生生长抑制作用（GI 50 = 3–80μM）。这些发现表明，HDAC8-选择性抑制剂具有作为抗癌药的潜力。
• COMPOUNDS, SUBSTRATES AND METHODS RELATED TO HISTONE DEACETYLASES
  申请人：The Broad Institute, Inc.

  公开号：US20160060679A1

  公开（公告）日：2016-03-03

  The invention relates to methods for the identification of compounds, peptides and proteins that can act as substrates for histone deacetylases. The invention further relates to compounds of Formula I: F 1 -X 1 -L 1 -X 2 -P 1 -X 3 -G 1 (Formula I) The invention relates to the treatment of diseases or disorders mediated by ARID1A (BAF250A).

  该发明涉及一种用于识别可作为组蛋白去乙酰化酶底物的化合物、肽和蛋白质的方法。该发明还涉及Formula I的化合物：F1-X1-L1-X2-P1-X3-G1（Formula I）。该发明涉及通过ARID1A（BAF250A）介导的疾病或障碍的治疗。
• Process-Controlled Regiodivergent Copper-Catalyzed Azide–Alkyne Cycloadditions: Tailor-made Syntheses of 4- and 5-Bromotriazoles from Bromo(phosphoryl)ethyne
  作者：Yasuhiro Okuda、Kazuto Imafuku、Yoshiyuki Tsuchida、Tomoyo Seo、Haruo Akashi、Akihiro Orita

  DOI：10.1021/acs.orglett.0c01681

  日期：2020.7.2

  We developed a regiodivergent syntheses of 4- and 5-bromo-substituted 1,2,3-triazoles in copper-catalyzed azide-alkyne cycloadditions (CuAACs) by taking advantage of bromo(phosphoryl)-ethyne 1 as a bromoethyne equivalent. A one-shot dephosphorylative CuAAC of 1 afforded 4-bromotriazoles, which was transformed into a histone deacetylase 8 (HDAC8)-selective inhibitor, NCC-149. However, the direct CuAAC catalyzed by CuI/Cu(OAc)(2) provided 5-bromo-4-phosphoryltriazoles. The consecutive nucleophilic substitution of the bromo group with thiols followed by MeOK-promoted dephosphorylation gave 5-thio-substituted triazoles.
• METHODS AND COMPOUNDS FOR THE TREATMENT OF GENETIC DISEASE
  申请人：Design Therapeutics, Inc.

  公开号：US20210238226A1

  公开（公告）日：2021-08-05

  The present disclosure relates to compounds and methods for modulating the expression of dmpk, atxn1, atxn2, atxn3, cacna1a, atxn7, ppp2r2br tbp, htt, jph3r ar, or atn1 and treating diseases and conditions in which dmpk, atxn1, atxn2, atxn3, cacna1a, atxn1, ppp2r2b, tbp, htt, jph3, ar, or atn1 plays an active role. The compound can be a transcription modulator molecule having a first terminus, a second terminus, and oligomeric backbone, wherein: a) the first terminus comprises a DNA-binding moiety capable of noncovalently binding to a nucleotide repeat sequence CAG or CTG; b) the second terminus comprises a protein-binding moiety binding to a regulatory molecule that modulates an expression of a gene comprising the nucleotide repeat sequence CAG or CTG; and c) the oligomeric backbone comprising a linker between the first terminus and the second terminus.
• US9745613B2
  申请人：——

  公开号：US9745613B2

  公开（公告）日：2017-08-29