4-[1,2,4]Triazol-1-yl-benzene-1,2-diamine | 131885-90-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-[1,2,4]Triazol-1-yl-benzene-1,2-diamine
• 英文别名: 4-(1,2,4-Triazol-1-yl)-o-phenylenediamine；4-(1,2,4-triazol-1-yl)benzene-1,2-diamine
• CAS: 131885-90-0
• 化学式: C₈H₉N₅
• 分子量: 175.193
• InChiKey: NUESBGFDOSMZCV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  82.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[1,2,4]Triazol-1-yl-benzene-1,2-diamine 在 三乙胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 78.25h， 生成 N-(5(6)-(1H-1,2,4-triazol-1-yl)-1H-benzimidazol-2-yl)(1H-pyrazol-3(5)-yl)acetamide
  参考文献：
  名称：

  2-氨基苯并咪唑衍生物作为蛋白激酶 CK1 Delta 新型抑制剂的结构研究

  摘要：

  蛋白激酶 CK1δ (CK1δ) 是一种丝氨酸-苏氨酸/激酶，可调节不同的生理过程，包括细胞周期、DNA 修复和细胞凋亡。 CK1δ 过度表达以及随之而来的特定蛋白质的过度磷酸化可能导致睡眠障碍、癌症和神经退行性疾病。 CK1δ 抑制剂在帕金森病、阿尔茨海默病和肌萎缩侧索硬化症的细胞和动物模型中显示出抗癌特性以及神经保护作用。为了获得新的 ATP 竞争性 CK1δ 抑制剂，合成了三组苯并咪唑-2-氨基衍生物 (1-32)，在稠合苯并环 (R) 上带有不同的取代基，在 2-氨基上带有不同的含吡唑酰基部分。性能最好的衍生物是在苯并咪唑-2-氨基支架 (13-32) 上具有 (1H-吡唑-3-基)-乙酰基部分的衍生物，其在低微摩尔范围内显示出 CK1δ 抑制剂活性。在 R 取代基中，5-氰基是最有利的，导致化合物具有纳摩尔效力（23，IC50 = 98.6 nM）。进行分子对接和动力学研究以指出抑制剂-激酶相互作用。

  DOI：

  10.3390/ph17040468
• 作为产物：
  描述：

  2-nitro-5-(1,2,4-triazol-1-yl)aniline 在 镍 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 4-[1,2,4]Triazol-1-yl-benzene-1,2-diamine
  参考文献：
  名称：

  Cardiotonic agents. Synthesis and cardiovascular properties of novel 2-arylbenzimidazoles and azabenzimidazoles

  摘要：

  Novel 2-arylbenzimidazoles and azabenzimidazoles were synthesized, and their inotropic action was evaluated. Changes in left ventricular pressure, dP/dt max, were measured as an index of cardiac contractility. The structural features that impart optimal inotropic activity are presented. The most potent compounds were evaluated orally in conscious dogs with implanted Konigsberg pressure transducers. To investigate the mechanism of action, the most potent compounds were tested for their calcium-sensitizing properties and their potential for the inhibition of phosphodiesterase. Two compounds, 1 and 4 1, showed interesting in vitro and oral activity without side effects. They have a more potent calcium-sensitizing effect than MCI-154 and are under futher investigation.

  DOI：

  10.1021/jm00101a024

文献信息

• 4-(Benzoimidazol-2-yl)-thiazole Compounds and Related Aza Derivatives
  申请人：Actelion Pharmaceuticals Ltd.

  公开号：US20140371204A1

  公开（公告）日：2014-12-18

  The invention relates to compounds of Formula (I) wherein ring A, X, (R 1 ) n , R 2 , R 3 , R 4 , R 4′ , R 5 , n, and p are as described in the description; to pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments, especially as modulators of the CXCR3 receptor.

  本发明涉及式(I)化合物，其中环A、X、(R1)n、R2、R3、R4、R4′、R5、n和p如描述中所述；涉及药用可接受的盐，以及将此类化合物用作药物，尤其是用作CXCR3受体的调节剂。
• [EN] 4-(BENZOIMIDAZOL-2-YL)-THIAZOLE COMPOUNDS AND RELATED AZA DERIVATIVES<br/>[FR] COMPOSÉS DE 4-(BENZOIMIDAZOL-2-YLE)-THIAZOLE ET DÉRIVÉS AZA ASSOCIÉS
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2013114332A1

  公开（公告）日：2013-08-08

  The invention relates to compounds of Formula (I) wherein ring A, X, (R1)n, R2, R3, R4, R4', R5, n, and p are as described in the description; to pharmaceutically acceptable salts thereof, and to the use of such compounds as medicaments, especially as modulators of the CXCR3 receptor.

  本发明涉及式(I)化合物，其中环A、X、(R1)n、R2、R3、R4、R4'、R5、n和p如描述中所述；涉及药用可接受的盐，以及将此类化合物用作药物，尤其是用作CXCR3受体的调节剂。
• Benzimidazole derivatives and pharmacologically acceptable salts thereof
  申请人：Taiho Pharmaceutical Co., Ltd.

  公开号：US06248768B1

  公开（公告）日：2001-06-19

  This invention provides a compound having both IL-4 production inhibitory activity and PDE (IV) inhibitory activity, represented by formula (I): and a pharmaceutical composition or a therapeutic agent for acute and chronic inflammatory diseases and an anti-allergic or anti-inflammatory agent, each of which comprising an effective amount of the compound and a pharmacological carrier. It also provides use of the compound of formula (I) for the production of the aforementioned pharmaceutical composition or therapeutic agent for acute and chronic inflammatory diseases and anti-allergic or anti-inflammatory agent, and a method for treating acute and chronic inflammatory diseases.

  本发明提供一种具有IL-4产生抑制活性和PDE（IV）抑制活性的化合物，其化学式表示为（I）：以及包含该化合物的有效量和药理载体的制药组合物或治疗剂，用于急性和慢性炎症性疾病的抗过敏或抗炎药物。还提供了化合物（I）的用途，用于制备上述的制药组合物或治疗剂，以及治疗急性和慢性炎症性疾病的方法。
• Design, Synthesis, and Pharmacological Evaluation of Benzimidazolo-thiazoles as Potent CXCR3 Antagonists with Therapeutic Potential in Autoimmune Diseases: Discovery of ACT-672125
  作者：Eva Caroff、Emmanuel A. Meyer、Päivi Äänismaa、Sylvie Froidevaux、Marcel Keller、Luca Piali

  DOI：10.1021/acs.jmedchem.2c00676

  日期：2022.9.8

  the benzimidazolo-thiazole core scaffold. The optimization of potency and the mitigation of an hERG liability are described. Further pharmacokinetic considerations led to the identification of the potent CXCR3 antagonist ACT-672125 (29). The compound showed good physicochemical properties and safety profile. In a proof-of-mechanism model of lung inflammation, ACT-672125 inhibited the recruitment of

  趋化因子受体 CXCR3 允许将先天性和适应性炎症免疫细胞选择性募集到发炎组织中。CXCR3 配体在暴露于促炎细胞因子后分泌。与 CXCR3 配体结合后，表达 CXCR3 的 T 淋巴细胞会迁移到炎症部位并促进组织损伤。因此，拮抗这种受体可能为患有以高浓度 CXCR3 配体为特征的自身免疫性疾病的患者提供临床益处。在这里，我们报告了我们的 CXCR3 发现计划的第二部分，我们探索了苯并咪唑并噻唑核心支架。描述了效力的优化和hERG责任的减轻。进一步的药代动力学考虑导致了有效的 CXCR3 拮抗剂 ACT-672125 ( 29）。该化合物显示出良好的物理化学性质和安全性。在肺部炎症的机制证明模型中，ACT-672125 以剂量依赖性方式抑制表达 CXCR3 的 T 细胞募集到发炎的肺部。
• BENZIMIDAZOLE DERIVATIVES AND PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：TAIHO PHARMACEUTICAL COMPANY, LIMITED

  公开号：EP0974589A1

  公开（公告）日：2000-01-26

  This invention provides a compound having both IL-4 production inhibitory activity and PDE (IV) inhibitory activity, represented by formula (I): [wherein A represents a triazole group; R1 and R2 may be the same or different from each other and each represents an aliphatic hydrocarbon radical which may have an alicyclic or aromatic hydrocarbon radical or an alicyclic hydrocarbon radical; R3 represents hydrogen atom or a substituent group; and R4 represents a hydrogen atom or a protective group of the nitrogen atom], and a pharmaceutical composition, a therapeutic or preventive agent for acute and chronic inflammatory diseases and an anti-allergic or anti-inflammatory agent, each of which comprising an effective amount of the compound and a pharmacological carrier. It also provides use of the compound of formula (I) for the production of the aforementioned pharmaceutical composition, therapeutic or preventive agent for acute and chronic inflammatory diseases and anti-allergic or anti-inflammatory agent, and a method for treating and/or preventing acute and chronic inflammatory diseases.

  本发明提供了一种同时具有IL-4产生抑制活性和PDE（IV）抑制活性的化合物，由式（I）表示： [其中 A 代表三唑基团；R1 和 R2 可以彼此相同或不同，并且各自代表脂肪族烃基，该烃基可以具有脂环族或芳香族烃基或脂环族烃基；R3 代表氢原子或取代基团；以及 R4 代表氢原子或氮原子的保护基团]，以及一种药物组合物、急性和慢性炎症性疾病的治疗剂或预防剂以及抗过敏剂或抗炎剂，其中每种药物组合物包括有效量的该化合物和药理学载体。本发明还提供了式（I）化合物用于生产上述药物组合物、急慢性炎症疾病的治疗或预防剂和抗过敏或抗炎剂的用途，以及治疗和/或预防急慢性炎症疾病的方法。