4-(5-氰基吡啶-2-基)哌嗪-1-羧酸叔丁酯 | 683274-61-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 4-(5-氰基吡啶-2-基)哌嗪-1-羧酸叔丁酯
• 中文别名: 5-氰基-2-[4-丁氧基羰基（哌嗪子）]吡啶
• 英文名称: tert-butyl 4-(5-cyanopyridine-2-yl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-(5-cyanopyridin-2-yl)piperazine-1-carboxylate；tert-butyl 4-(5-cyano-2-pyridyl)piperazine-1-carboxylate；t-butyl4-(5-cyanopyridin-2-yl)piperazin-1-carboxylate
• CAS: 683274-61-5
• 化学式: C₁₅H₂₀N₄O₂
• mdl: MFCD03407524
• 分子量: 288.349
• InChiKey: CUKYCLGXUNOINC-UHFFFAOYSA-N

物化性质

• 熔点：
  126-128°C

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.533
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  4-(5-氰基吡啶-2-基)哌嗪-1-羧酸叔丁酯 在 盐酸 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.67h， 生成 6-(4-[[3-(2-[[6-oxo-5-(trifluoromethyl)-1,6-dihydropyridazin-4-yl]oxy]ethoxy)phenyl]carbonyl]piperazin-1-yl)pyridine-3-carbonitrile
  参考文献：
  名称：

  PYRIDAZINONES AS PARP7 INHIBITORS

  摘要：

  本发明涉及吡啶并嗪酮和相关化合物，它们是PARP7的抑制剂，并且在癌症治疗中很有用。

  公开号：

  US20190330194A1
• 作为产物：
  描述：

  6-氯-3-氰基吡啶 、 N-Boc-哌嗪 在 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 4-(5-氰基吡啶-2-基)哌嗪-1-羧酸叔丁酯
  参考文献：
  名称：

  LipE 指导发现异丙基苯基哒嗪作为泛酸激酶调节剂

  摘要：

  泛酸激酶 (PANK) 是细胞内辅酶 A 水平的关键调节剂，已成为治疗神经和代谢疾病的有吸引力的靶标。本报告描述了一种新化学系列泛酸竞争性 PANK 抑制剂的优化、合成和完整的构效关系。使用源自人 PANK3 IC 50的亲脂性配体效率 (LipE) 通过优化高通量筛选命中获得有效的药物样分子指导配体开发的价值。确定了具有优化指数抑制剂的 PANK3 的 X 射线晶体结构，以合理化新出现的结构活性关系。分析揭示了哒嗪和 R306' 之间的关键双齿氢键相互作用是优化中观察到的 LipE 增益的主要贡献者。本研究产生了一系列易于处理的 PANK3 调节剂，具有纳摩尔效力、优异的 LipE 值、理想的物理化学性质和明确的结构结合模式。

  DOI：

  10.1016/j.bmc.2021.116504

文献信息

• [EN] OGA INHIBITOR COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS D'OGA
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2021123291A1

  公开（公告）日：2021-06-24

  The present invention relates to O-GlcNAc hydrolase (OGA) inhibitors. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes for preparing such compounds and compositions, and to the use of such compounds and compositions for the prevention and treatment of disorders in which inhibition of OGA is beneficial, such as tauopathies, in particular Alzheimer's disease or progressive supranuclear palsy; and neurodegenerative diseases accompanied by a tau pathology, in particular amyotrophic lateral sclerosis or frontotemporal lobe dementia caused by C9ORF72 mutations; or alpha synucleinopathies, in particular Parkinson's disease, dementia due to Parkinson's (or neurocognitive disorder due to Parkinson's disease), dementia with Lewy bodies, multiple system atrophy, or alpha synucleinopathy caused by Gaucher's disease.

  本发明涉及O-GlcNAc水解酶（OGA）抑制剂。该发明还涉及包含这类化合物的药物组合物，制备这类化合物和组合物的方法，以及利用这类化合物和组合物预防和治疗抑制OGA有益的疾病的用途，例如tau病变，特别是阿尔茨海默病或进行性上行性核瘫痪；以及伴有tau病理的神经退行性疾病，特别是由C9ORF72突变引起的肌萎缩侧索硬化或额颞叶痴呆；或α-突触核蛋白病，特别是帕金森病、帕金森病引起的痴呆（或由帕金森病引起的神经认知障碍）、带有Lewy小体的痴呆、多系统萎缩，或由高雪氏病引起的α-突触核蛋白病。
• An expedient Pd/DBU mediated cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6]
  作者：Dengyou Zhang、Haifeng Sun、Lei Zhang、Yu Zhou、Chunpu Li、Hualiang Jiang、Kaixian Chen、Hong Liu

  DOI：10.1039/c2cc17468e

  日期：——

  A practical Pd(PPh3)4/DBU catalytic system for the synthesis of pharmaceutically relevant aminopyridine nitrile intermediates, as well as a variety of other aryl nitriles using non-toxic K4[Fe(CN)6] has been developed. The key features of our new protocol for cyanation lie in that the reaction can be carried out with readily available Pd(PPh3)4 under mild and green conditions, even without the assistance of other ligands.

  一种用于合成具有药物相关性的氨基吡啶腈中间体的实用Pd(PPh3)4/DBU催化体系，以及其他多种使用无毒K4[Fe(CN)6]的芳基腈，已经开发出来。我们新方案中氰化的关键特点在于，反应可以在温和且环保的条件下，使用易于获得的Pd(PPh3)4进行，甚至无需其他配体的辅助。
• NOVEL 3-(4(BENZYLOXY)PHENYL)HEX-4-INOIC ACID DERIVATIVE, METHOD OF PREPARING SAME AND PHARMACEUTICAL COMPOSITION FOR PREVENTING AND TREATING METABOLIC DISEASE INCLUDING SAME AS EFFECTIVE INGREDIENT
  申请人：HYUNDAI PHARM CO., LTD

  公开号：US20160024063A1

  公开（公告）日：2016-01-28

  The present invention relates to a novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, a preparation method thereof, and a pharmaceutical composition comprising the same as an active ingredient for the prevention and treatment of metabolic disease. The novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention has excellent activities of activating GPR40 protein and promoting insulin secretion accordingly but has no toxicity when co-administered with other drugs. That is, the novel 3-(4-(benzyloxy)phenyl)hex-4-inoic acid derivative, the optical isomer thereof, or the pharmaceutically acceptable salt thereof of the present invention can be co-administered with other drugs and can promote the activation of GPR40 protein significantly, so that the composition comprising the same as an active ingredient can be efficiently used as a pharmaceutical composition for the prevention and treatment of metabolic disease such as obesity, type I diabetes, type II diabetes, incompatible glucose tolerance, insulin resistance, hyperglycemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, dyslipidemia, and syndrome X, etc.

  本发明涉及一种新型的3-(4-(苄氧基)苯基)己-4-羧酸衍生物，其制备方法以及包含该衍生物作为活性成分的药物组合物，用于预防和治疗代谢性疾病。本发明的这种新型的3-(4-(苄氧基)苯基)己-4-羧酸衍生物、其光学异构体或其药用可接受盐，对于激活GPR40蛋白并相应地促进胰岛素分泌具有优良活性，且在与其他药物联合使用时没有毒性。也就是说，本发明的这种新型的3-(4-(苄氧基)苯基)己-4-羧酸衍生物、其光学异构体或其药用可接受盐，可以与其他药物联合使用，并且能显著促进GPR40蛋白的激活，使得包含其作为活性成分的组合物能有效地用作预防和治疗诸如肥胖、I型糖尿病、II型糖尿病、糖耐量异常、胰岛素抵抗、高血糖、高脂血症、高甘油三酯血症、高胆固醇血症、血脂异常和X综合症等代谢性疾病的药物组合物。
• Synthesis of new and potent analogues of anti-tuberculosis agent 5-nitro-furan-2-carboxylic acid 4-(4-benzyl-piperazin-1-yl)-benzylamide with improved bioavailability
  作者：Rajendra P. Tangallapally、Robin E.B. Lee、Anne J.M. Lenaerts、Richard E. Lee

  DOI：10.1016/j.bmcl.2006.02.048

  日期：2006.5

  bioavailability, a new series of analogues was successfully synthesized using three modification schemes: replacement of the benzyl group on the piperazine C-ring with carbamate and urea functional groups; introduction of a nitrogen atom into the aromatic ring-B; and expansion of the ring-B to a bicyclic tetrahydroisoquinoline moiety. These modifications retained strong activity and in some case gained superior

  以前，在我们的抗结核药物发现计划中已经确定了先导化合物5-硝基呋喃-2-羧酸4-（4-苄基哌嗪-1-基）-苄基酰胺。尽管该化合物具有出色的体外活性，但由于其结构特征导致快速的代谢裂解和吸收不良，因此未能达到预期的体内分布，因此限制了其生物利用度。为了提高生物利用度，使用三种修饰方案成功合成了一系列新的类似物：用氨基甲酸酯和尿素官能团取代哌嗪C环上的苄基；将氮原子引入芳族环-B中；环B膨胀成双环四氢异喹啉部分。
• 3-ARYL-5-SUBSTITUTED-ISOQUINOLIN-1-ONE COMPOUNDS AND THEIR THERAPEUTIC USE
  申请人：INSTITUTE OF CANCER RESEARCH: ROYAL CANCER HOSPITAL (THE)

  公开号：US20150099732A1

  公开（公告）日：2015-04-09

  The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain 3-aryl-5-substituted-2H-isoquinolin-1-one compounds that, inter alia, inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.) and/or Wnt signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to inhibit Wnt signalling; to treat disorders that are ameliorated by the inhibition of PARP (e.g., PARP1, TNKS1, TNKS2, etc.); to treat disorders that are ameliorated by the inhibition of Wnt signalling; to treat proliferative conditions such as cancer, etc.

  本发明通常涉及治疗化合物领域。更具体地，本发明涉及某些3-芳基-5-取代-2H-异喹啉-1-酮化合物，该化合物在抑制PARP（例如PARP1，TNKS1，TNKS2等）和/或Wnt信号传导方面具有作用。本发明还涉及包含这些化合物的药物组合物，以及利用这些化合物和组合物，在体内和体外，来抑制PARP（例如PARP1，TNKS1，TNKS2等）；抑制Wnt信号传导；治疗通过抑制PARP（例如PARP1，TNKS1，TNKS2等）改善的疾病；治疗通过抑制Wnt信号传导改善的疾病；治疗癌症等增生症状。