3-溴-4-甲基-1,2,4-三唑 | 16681-73-5

• 物质功能分类: 医药中间体 - 杂环化合物
• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 中文名称: 3-溴-4-甲基-1,2,4-三唑
• 中文别名: 3-溴-4-甲基-1,2,4-噻唑
• 英文名称: 5-Brom-4-methyl-1,2,4-triazol
• 英文别名: 3-bromo-4-methyl-4H-1,2,4-triazole；3-bromo-4-methyl-1,2,4-triazole
• CAS: 16681-73-5
• 化学式: C₃H₄BrN₃
• mdl: MFCD10696422
• 分子量: 161.989
• InChiKey: PYMVKLCRJYMSGC-UHFFFAOYSA-N

物化性质

• 沸点：
  255.9±23.0 °C(Predicted)
• 密度：
  1.93±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  7
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  3-溴-4-甲基-1,2,4-三唑 、 4-[5-bromo-1-(4-fluorophenyl)-1H-indol-3-yl]piperidine-1-carboxylic acid tert-butyl ester 在 正丁基锂 、 zinc(II) chloride 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.55h， 以31%的产率得到4-[1-(4-fluorophenyl)-5-(1-methyl-1,3,4-triazol-2-yl)-1H-indol-3-yl]piperidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  抗精神病药sertindole的5-杂芳基取代的类似物的合成和结构亲和关系研究。一类新的高度选择性的α（1）肾上腺素受体拮抗剂。

  摘要：

  描述了一类新的5-杂芳基取代的1-（4-氟苯基）-3-（4-哌啶基）-1H-吲哚，它们具有高选择性，并且具有潜在的CNS活性α1-肾上腺素受体拮抗剂。所述化合物衍生自抗精神病药斯多吲哚。优化了5-杂芳基取代基和哌啶氮原子上的取代基的结构亲和性，从而优化了对α1肾上腺素受体的亲和力以及对多巴胺（D（1-4））和5-羟色胺（5-HT）的选择性（1A-1B）和5-HT（2A，2C））受体。获得的最具选择性的化合物3- [4- [1-（4-氟苯基）-5-（1-甲基-1,2,4-三唑-3-基）-1H-吲哚-3-基] -1 -哌啶基]丙腈（15c）对alpha（1a），alpha（1b）和alpha（1d）肾上腺素受体亚型的亲和力分别为0.99、3.2和9.0 nM，对多巴胺D2，D3和D4以及5-羟色胺5-HT（2A）和5-HT（2C）的肾上腺素α（1a）受体的选择性高于900，与哌唑嗪的选择性相当

  DOI：

  10.1021/jm020938y
• 作为产物：
  描述：

  4-甲基-1,2,4-三唑 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 氯仿 为溶剂， 以19%的产率得到3-溴-4-甲基-1,2,4-三唑
  参考文献：
  名称：

  Novel Small Molecule Bradykinin B₂ Receptor Antagonists

  摘要：

  Blockade of the bradykinin B, receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B, receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B-2 receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B-2 receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B-2 receptor, Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B-2 receptor antagonist 52e (JSM 10292), which showed the best overall properties.

  DOI：

  10.1021/jm9002445

文献信息

• [EN] INHIBITORS OF CBL-B AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS DE CBL-B ET LEURS PROCÉDÉS D'UTILISATION
  申请人：NURIX THERAPEUTICS INC

  公开号：WO2019148005A1

  公开（公告）日：2019-08-01

  Compounds, compositions, and methods for use in inhibiting the E3 enzyme Cbl-b in the ubiquitin proteasome pathway are disclosed. The compounds, compositions, and methods can be used to modulate the immune system, to treat diseases amenable to immune system modulation, and for treatment of cells in vivo, in vitro, or ex vivo.

  揭示了用于抑制泛素蛋白酶体途径中的E3酶Cbl-b的化合物、组合物和使用方法。这些化合物、组合物和方法可用于调节免疫系统，治疗适合免疫系统调节的疾病，并用于体内、体外或体外细胞的治疗。
• AOUIAL M.; BERNARDINI A.; VIALLEFONT PH., J. HETEROCYCL. CHEM., 1977, 14, NO 3, 397-400
  作者：AOUIAL M.、 BERNARDINI A.、 VIALLEFONT PH.

  DOI：——

  日期：——
• WO2024097953A1
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] 3-(6-PYRIDIN-3-YL)-2-[4-(4-METHYL-4H-1,2,4-TRIAZOL-3-YL)PIPERIDIN-1-YL]BENZONITRILE DERIVATIVES AND SIMILAR COMPOUNDS AS QPCTL AND QPCT INHIBITORS FOR THE TREATMENT OF CANCER<br/>[FR] DÉRIVÉS DE 3-(6-PYRIDIN-3-YL)-2-[4-(4-MÉTHYL-4H-1,2,4-TRIAZOL-3-YL)PIPÉRIDIN-1-YL]BENZONITRILE ET COMPOSÉS SIMILAIRES UTILISÉS EN TANT QU'INHIBITEURS DE QPCTL ET QPCT POUR LE TRAITEMENT DU CANCER
  申请人：[en]858 THERAPEUTICS, INC.

  公开号：WO2024020517A1

  公开（公告）日：2024-01-25

  Provided herein are compounds of formula (II) and formula (I) that are inhibitors of QPCTL and QPCT: (II) & (I) Also provided are pharmaceutical compositions comprising the compounds, as well as the compounds for use in methods for the treatment of cancer, neurodegenerative, inflammatory or autoimmune diseases. A exemplary compound is e.g. 3-(6-fluoropyridin-3-yl)-2-[4-(4- methyl-4H-1,2,4-triazol-3-yl)piperidin-1-yl]benzonitrile (example 1): (1) Pharmacological data is provided.
• Novel Small Molecule Bradykinin B₂ Receptor Antagonists
  作者：Christoph Gibson、Karsten Schnatbaum、Jochen R. Pfeifer、Elsa Locardi、Matthias Paschke、Ulf Reimer、Uwe Richter、Dirk Scharn、Alexander Faussner、Thomas Tradler

  DOI：10.1021/jm9002445

  日期：2009.7.23

  Blockade of the bradykinin B, receptor provides therapeutic benefit in hereditary angioedema (HAE) and potentially in many other diseases. Herein, we describe the development of highly potent B, receptor antagonists with a molecular weight of approximately 500 g/mol. First, known quinoline-based B-2 receptor antagonists were stripped down to their shared core motif 53, which turned out to be the minimum pharmacophore. Targeted modifications of 53 resulted in the highly water-soluble lead compound 8a. Extensive exploration of its structure-activity relationship resulted in a series of highly potent B-2 receptor antagonists, featuring a hydrogen bond accepting functionality, which presumably interacts with the side chain of Asn-107 of the B-2 receptor, Optimization of the microsomal stability and cytochrome P450 inhibition eventually led to the discovery of the highly potent and orally available B-2 receptor antagonist 52e (JSM 10292), which showed the best overall properties.

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