tert-butyl 4-(4-(hydrazinecarbonyl)-1H-1,2,3-triazol-1-yl)piperidine-1-carboxylate | 1207740-65-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl 4-(4-(hydrazinecarbonyl)-1H-1,2,3-triazol-1-yl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[4-(hydrazinecarbonyl)triazol-1-yl]piperidine-1-carboxylate
• CAS: 1207740-65-5
• 化学式: C₁₃H₂₂N₆O₃
• 分子量: 310.356
• InChiKey: KVUZOLRXPRAMBO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(4-(hydrazinecarbonyl)-1H-1,2,3-triazol-1-yl)piperidine-1-carboxylate 在 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 18.75h， 生成 2-(1-(1-ethylpiperidin-4-yl)-1H-1,2,3-triazol-4-yl)-5-phenyl-1,3,4-oxadiazole
  参考文献：
  名称：

  Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents

  摘要：

  Sodium bisulfite has been reported first time for the synthesis of 2,5-disubstituted 1,3,4-oxadiazole using microwave and conventional method in ethanol-water. The yields obtained are in the range of 90-95% using microwave and 87-91% using conventional method. All the synthesized compounds (8a-8s) are novel and were evaluated for their in vitro antifungal activity. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Some of the compounds from the series like 8k was equipotent with miconazole against Candida albicans and Fusarium oxysporum. Also compound 8n was equipotent with miconazole against F. oxysporum. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.120
• 作为产物：
  描述：

  N-叔丁氧羰基-4-哌啶酮 在 sodium tetrahydroborate 、 copper(l) iodide 、 sodium azide 、 一水合肼 、 三乙胺 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 30.0h， 生成 tert-butyl 4-(4-(hydrazinecarbonyl)-1H-1,2,3-triazol-1-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents

  摘要：

  Sodium bisulfite has been reported first time for the synthesis of 2,5-disubstituted 1,3,4-oxadiazole using microwave and conventional method in ethanol-water. The yields obtained are in the range of 90-95% using microwave and 87-91% using conventional method. All the synthesized compounds (8a-8s) are novel and were evaluated for their in vitro antifungal activity. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Some of the compounds from the series like 8k was equipotent with miconazole against Candida albicans and Fusarium oxysporum. Also compound 8n was equipotent with miconazole against F. oxysporum. (c) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.120

文献信息

• [EN] 1, 3, 4-OXADIAZOLE DERIVATIVES AND USES THEREOF<br/>[FR] DÉRIVÉS DE 1, 3, 4-OXADIAZOLE ET LEURS UTILISATIONS
  申请人：ALXERION BIOTECH CORP

  公开号：WO2020060963A1

  公开（公告）日：2020-03-26

  The disclosure provides 1, 3, 4-oxadiazole derivatives useful for stemming bleeding and for treating cancer.

  该披露提供了用于止血和治疗癌症的1,3,4-噁二唑衍生物。
• 1,2,3-TRIAZOLE DERIVATIVES AND USES THEREOF
  申请人：Alxerion Biotech LLC

  公开号：US20210317113A1

  公开（公告）日：2021-10-14

  Provided herein are 1,2,3-triazole derivatives and methods of use thereof.

  本文提供了1,2,3-三唑衍生物及其使用方法。
• Synthesis, Antifungal Activity, and Docking Study of Some New 1,2,4-triazole Analogs
  作者：Jaiprakash N. Sangshetti、Deepak K. Lokwani、Aniket P. Sarkate、Devanand B. Shinde

  DOI：10.1111/j.1747-0285.2011.01178.x

  日期：2011.11

  Synthesis of new series of 1,2,4‐triazole with 1,2,3‐triazole and piperidine ring using ZrOCl2·8H2O as a catalyst in ethanol has been described. The yields obtained are in the range of 80–85%. All the synthesized compounds (3a–3o) are novel and were evaluated for their in vitro antifungal activities using standard agar method. Docking study of the newly synthesized compounds was performed, and results

  已经描述了使用ZrOCl 2 ·8H 2 O作为催化剂在乙醇中合成具有1,2,3-三唑和哌啶环的新系列1,2,4-三唑。获得的产率在80-85％的范围内。所有合成的化合物（3a - 3o）都是新颖的，并使用标准琼脂法对其体外抗真菌活性进行了评估。对新合成的化合物进行了对接研究，结果表明，所有新化合物在真菌酶P450细胞色素羊毛甾醇14α-脱甲基酶的活性位点具有相似的结合模式。
• 1,2,3-Triazole Derivatives as Novel Antifibrinolytic Drugs
  作者：Oriol Bosch-Sanz、Yvette Rabadà、Xevi Biarnés、Javier Pedreño、Luis Caveda、Mercedes Balcells、Jordi Martorell、David Sánchez-García

  DOI：10.3390/ijms232314942

  日期：——

  Fibrinolysis is a natural process that ensures blood fluidity through the removal of fibrin deposits. However, excessive fibrinolytic activity can lead to complications in different circumstances, such as general surgery or severe trauma. The current antifibrinolytic drugs in the market, aminocaproic acid (EACA) and tranexamic acid (TXA), require high doses repetitively to maintain their therapeutic effect. These high doses are related to a number of side effects such as headaches, nasal symptoms, or gastrointestinal discomfort and severely limit their use in patients with renal impairment. Therefore, the discovery of novel antifibrinolytics with a higher specificity and lower dosage could vastly improve the applicability of these drugs. Herein, we synthesized a total of ten compounds consisting of a combination of three key moieties: an oxadiazolone, a triazole, and a terminal amine. The IC50 of each compound was calculated in our clot lysis assays, and the best candidate (1) provided approximately a 2.5-fold improvement over the current gold standard, TXA. Molecular docking and molecular dynamics were used to perform a structure–activity relationship (SAR) analysis with the lysine binding site in the Kringle 1 domain of plasminogen. This analysis revealed that 1,2,3-triazole was crucial for the activity, enhancing the binding affinity through pi–pi stacking and polar interactions with Tyr72. The results presented in this work open the door to further investigate this new family as potential antifibrinolytic drugs.

  纤溶是一种自然过程，通过消除纤维蛋白沉积物来确保血液流动性。然而，在不同情况下，如普通手术或严重创伤中，过度的纤溶活性可能导致并发症。目前市场上的抗纤溶药物，氨甲环酸（EACA）和曲马多酸（TXA），需要高剂量反复使用以维持其治疗效果。这些高剂量与头痛、鼻症状或胃肠不适等一些副作用有关，并严重限制了它们在肾功能不全患者中的使用。因此，发现具有更高特异性和更低剂量的新型抗纤溶药物可以极大地改善这些药物的适用性。在这里，我们合成了十种化合物，包括三种关键基团的组合：氧代唑酮、三唑和末端胺基。每种化合物的IC50在我们的凝血溶解试验中被计算出来，最佳候选化合物（1）相比当前的金标准TXA提供了大约2.5倍的改进。分子对接和分子动力学被用来在纤溶酶原的Kringle 1结构域的赖氨酸结合位点中进行结构-活性关系（SAR）分析。这个分析揭示了1,2,3-三唑对活性至关重要，通过pi-pi堆积和与Tyr72的极性相互作用增强了结合亲和力。本研究所提出的结果为进一步研究这种新的家族作为潜在的抗纤溶药物打开了大门。
• One pot synthesis and SAR of some novel 3-substituted 5,6-diphenyl-1,2,4-triazines as antifungal agents
  作者：Jaiprakash N. Sangshetti、Devanand B. Shinde

  DOI：10.1016/j.bmcl.2009.11.048

  日期：2010.1

  An improved protocol for the synthesis of a novel series of 1,2,4-triazines possessing 1,2,3-triazole and piperidine ring using 1-(1-substituted piperidin-4-yl)-1H-1,2,3-triazole-4-carbohydrazide, benzil, ammonium acetate and ZrOCl2 center dot 8H(2)O as a catalyst in ethanol-water has been presented. The yields obtained are in the range of 87-94%. All the synthesized compounds (4a-4l) are novel and were evaluated for their in vitro antifungal activity. SAR for the series has been developed by comparing their MIC values with miconazole and fluconazole. Based on activity data SAR for the series has been developed. Compound 4c from the series was equipotent to miconazole against Candida albicans (MIC-25), Aspergillus niger (MIC-12.5) and Cryptococcus neoformans (MIC-25). Compound 4d was equipotent with miconazole against all tested organisms except Cryptococcus neoformans. Also compound 4i was equipotent with miconazole against C. albicans, A. niger and Fusarium oxysporum. (C) 2009 Elsevier Ltd. All rights reserved.