4,5,6,7-四氢-1,2,3-三氮唑并[1,5-A]吡嗪 | 123291-54-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: 4,5,6,7-四氢-1,2,3-三氮唑并[1,5-A]吡嗪
• 英文名称: 4,5,6,7-tetrahydro-1,2,3-triazolo[1,5-a]pyrazine
• 英文别名: 4,5,6,7-tetrahydrotriazolo[1,5-a]pyrazine
• CAS: 123291-54-3
• 化学式: C₅H₈N₄
• mdl: MFCD09802206
• 分子量: 124.145
• InChiKey: RMXGROKBRJVWRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 储存条件：
  室温且干燥

反应信息

• 作为反应物：
  描述：

  4,5,6,7-四氢-1,2,3-三氮唑并[1,5-A]吡嗪 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-3-amino-4-(2,4,5-trifluorophenyl)-1-(6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazin-5(4H)-yl)butan-1-one fumaric acid
  参考文献：
  名称：

  发现有效的衍生自带有取代的[1,2,3]-三唑并哌啶的β-氨基酰胺的二肽基肽酶IV抑制剂，用于治疗2型糖尿病

  摘要：

  合成了一系列新颖的[1,2,3]-三唑并哌啶衍生物5a-5y，并作为二肽基肽酶IV（DPP-4）的抑制剂进行了评估，用于治疗2型糖尿病，大多数化合物具有出色的体外药效（ 针对DPP-4的IC 50 <50 nM）。在这些化合物中，对DPP-4具有强大的体外活性和良好的药代动力学特征的化合物5d在ICR小鼠的口服葡萄糖耐量试验（OGTT）中表现出明显的体内功效。基于这些特性，选择化合物5d作为治疗2型糖尿病的潜在新候选药物。

  DOI：

  10.1016/j.bmcl.2011.01.086
• 作为产物：
  描述：

  N-benzyl-N-(2-hydroxyethyl)prop-2-yn-1-amine 在 吡啶 、 氯化亚砜 、 氢气 、 palladium(II) hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 10.0h， 生成 4,5,6,7-四氢-1,2,3-三氮唑并[1,5-A]吡嗪
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Novel Fused Heterocycles-Linked Triazoles with Good Activity and Water Solubility

  摘要：

  Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]-triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.

  DOI：

  10.1021/jm4016284

文献信息

• [EN] COMPOUNDS THAT INHIBIT MCL-1 PROTEIN<br/>[FR] COMPOSÉS INHIBANT LA PROTÉINE MCL-1
  申请人：AMGEN INC

  公开号：WO2018183418A1

  公开（公告）日：2018-10-04

  Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula (I), or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

  本文提供了髓样细胞白血病1蛋白（Mcl-1）抑制剂，其制备方法，相关的药物组合物，以及使用这些物质的方法。例如，本文提供了化合物的化学式（I）或其立体异构体；以及这些化合物的药用盐和含有这些化合物的药物组合物。本文提供的化合物和组合物可以用于治疗癌症等疾病或症状。
• An improved, scalable synthesis of Notum inhibitor LP-922056 using 1-chloro-1,2-benziodoxol-3-one as a superior electrophilic chlorinating agent
  作者：Nicky J Willis、Elliott D Bayle、George Papageorgiou、David Steadman、Benjamin N Atkinson、William Mahy、Paul V Fish

  DOI：10.3762/bjoc.15.271

  日期：——

  negative regulator of the Wnt signalling pathway by mediating the depalmitoleoylation of Wnt proteins. LP-922056 (1) is an orally active inhibitor of Notum. We are investigating the role of Notum in modulating Wnt signalling in the central nervous system and wished to establish if 1 would serve as a peripherally restricted control. An accessible and improved synthetic route would allow 1 to become more readily

  背景：羧酸酯酶Notum已被证明通过介导Wnt蛋白的去棕榈油酰化作用而成为Wnt信号通路的关键负调控因子。LP-922056（1）是Notum的口服活性抑制剂。我们正在研究Notum在调节中枢神经系统中Wnt信号传导中的作用，并希望确定1是否可以作为周围受限的控制。一种易于使用且经过改进的合成途径将使1可以更容易地用作化学工具，以探索Notum的基本生物学并建立靶标验证，以支持新的药物发现计划。
• [EN] INDAZOLE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF HERPES VIRUSES<br/>[FR] DÉRIVÉS D'INDAZOLE ET LEURS MÉTHODES D'UTILISATION DANS LE TRAITEMENT DE L'HERPÈS VIRUS
  申请人：MERCK SHARP & DOHME

  公开号：WO2021126804A1

  公开（公告）日：2021-06-24

  The present invention relates to novel Indazole Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, X, Y, Z, R1 R5 and R6 are as defined herein. The present invention also relates to compositions comprising at least one Indazole Derivative, and methods of using the Indazole Derivatives for treating or preventing a herpesvirus infection in a patient.

  本发明涉及公式（I）的新型吲唑衍生物及其药用可接受盐，其中A、X、Y、Z、R1、R5和R6如本文所定义。本发明还涉及包含至少一种吲唑衍生物的组合物，以及使用吲唑衍生物治疗或预防患者的疱疹病毒感染的方法。
• [EN] BICYCLIC BIS-HETEROARYL DERIVATIVES AS MODULATORS OF PROTEIN AGGREGATION<br/>[FR] DÉRIVÉS BIS-HÉTÉROARYLIQUES BICYCLIQUES UTILISÉS EN TANT QUE MODULATEURS DE L'AGRÉGATION DES PROTÉINES
  申请人：UCB BIOPHARMA SPRL

  公开号：WO2018138088A1

  公开（公告）日：2018-08-02

  The present invention relates to certain bicyclic bis-heteroaryl compounds of Formula (I), pharmaceutical compositions containing them, and methods of using them, including methods for preventing, reversing, slowing, or inhibiting protein aggregation, and methods of treating diseases that are associated with protein aggregation, including neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease, Lewy body disease, Parkinson's disease with dementia, fronto-temporal dementia, Huntington's Disease, amyotrophic lateral sclerosis, and multiple system atrophy, and cancer including melanoma.

  本发明涉及具有化学式(I)的某些双环杂环芳基化合物，包含它们的药物组合物，以及使用它们的方法，包括预防、逆转、减缓或抑制蛋白聚集的方法，以及治疗与蛋白聚集相关的疾病的方法，包括帕金森病、阿尔茨海默病、路易体病、帕金森病伴痴呆、额颞叶痴呆、亨廷顿病、肌萎缩侧索硬化和多系统萎缩等神经退行性疾病，以及包括黑色素瘤在内的癌症。
• Development of Predictive Classification Models for Whole Cell Antimycobacterial Activity of Benzothiazinones
  作者：Sebastian Schieferdecker、Freddy A. Bernal、K. Philip Wojtas、François Keiff、Yan Li、Hans-Martin Dahse、Florian Kloss

  DOI：10.1021/acs.jmedchem.2c00098

  日期：2022.5.12

  against Mycobacterium tuberculosis. However, relationships between their structural properties and whole cell activity remain poorly predictable. Herein, we present the synthesis and antimycobacterial evaluation of a diverse set of BTZs. High potency was predominantly achieved by piperidine and piperazine substitutions, whereupon three compounds were identified as promising candidates, showing preferable

  硝基苯并噻嗪酮 (BTZ) 是一类非常有效的抗结核分枝杆菌的抗生素. 然而，它们的结构特性和全细胞活性之间的关系仍然很难预测。在此，我们介绍了多种 BTZ 的合成和抗分枝杆菌评估。高效力主要通过哌啶和哌嗪取代来实现，因此三种化合物被确定为有希望的候选物，显示出较好的代谢稳定性。效力和计算的结合能之间缺乏相关性表明靶抑制不是获得合适的抗分枝杆菌剂的唯一要求。相比之下，通过广泛验证的机器学习模型成功地完成了全细胞活动类别的预测。通过对大量报告的 BTZ 进行 >70% 的正确类别预测，进一步验证了卓越模型的性能。