3-(哌啶-4-基)丙基氨基甲酸叔丁酯 | 885268-87-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 3-(哌啶-4-基)丙基氨基甲酸叔丁酯
• 中文别名: N-[3-(哌啶-4-基)丙基]氨基甲酸叔丁酯
• 英文名称: tert-butyl (3-(piperidin-4-yl)propyl)carbamate
• 英文别名: Tert-butyl 3-(piperidin-4-YL)propylcarbamate；tert-butyl N-(3-piperidin-4-ylpropyl)carbamate
• CAS: 885268-87-1
• 化学式: C₁₃H₂₆N₂O₂
• 分子量: 242.362
• InChiKey: BCVMKVMKZSEQIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  50.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  3-(哌啶-4-基)丙基氨基甲酸叔丁酯 在 sodium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 24.08h， 生成 4-[4-(2-Acetamidoethyl)piperidin-1-yl]thieno[3,2-d]pyrimidine-6-carboxamide
  参考文献：
  名称：

  Discovery of Thieno[3,2-d]pyrimidine-6-carboxamides as Potent Inhibitors of SIRT1, SIRT2, and SIRT3

  摘要：

  The sirtuins SIRT1, SIRT2, and SIRT3 are NAD(+) dependent deacetylases that are considered potential targets for metabolic, inflammatory, oncologic, and neurodegenerative disorders. Encoded library technology (ELT) was used to affinity screen a 1.2 million heterocycle enriched library of DNA encoded small molecules, which identified pan-inhibitors of SIRT1/2/3 with nanomolar potency (e.g., 11c: IC50 = 3.6, 2.7, and 4.0 nM for SIRT1, SIRT2, and SIRT3, respectively). Subsequent SAR studies to improve physiochemical properties identified the potent drug like analogues 28 and 31. Crystallographic studies of 11c, 28, and 31 bound in the SIRT3 active site revealed that the common carboxamide binds in the nicotinamide C-pocket and the aliphatic portions of the inhibitors extend through the substrate channel, explaining the observable SAR. These pan SIRT1/2/3 inhibitors, representing a novel chemotype, are significantly more potent than currently available inhibitors, which makes them valuable tools for sirtuin research.

  DOI：

  10.1021/jm400204k
• 作为产物：
  描述：

  3-(1-Benzyl-piperidin-4-yl)-propan-1-ol 在 氯化亚砜 、 palladium on activated charcoal 、 氢气 、 palladium(II) hydroxide 、 potassium carbonate 、 一水合肼 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 54.0h， 生成 3-(哌啶-4-基)丙基氨基甲酸叔丁酯
  参考文献：
  名称：

  AURKA 선택적 분해 유도 화합물

  摘要：

  本发明涉及一种能够诱导AURKA（ Aurora kinase A）选择性分解的新型化合物，具体来说，它是一种双功能化合物，其中包含与AURKA结合的基团和与E3泛素连接酶结合的基团，并且这两个基团通过化学连接基团相连。此外，本发明还提供这种化合物的制备方法及其用途。根据本发明的化合物在AURKA相关疾病的预防或治疗中具有应用价值。

  公开号：

  KR20240008889A

文献信息

• [EN] THIENO[3,2-D]PYRIMIDINE-6-CARBOXAMIDES AND ANALOGUES AS SIRTUIN MODULATORS<br/>[FR] THIÉNO[3,2-D]PYRIMIDINE-6-CARBOXAMIDES ET ANALOGUES COMME MODULATEUR DE SIRTUINE
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2014138562A1

  公开（公告）日：2014-09-12

  Provided herein are novel substituted thieno[3,2-d]pyrimidine-6-carboxamide sirtuin inhibitors and methods of use thereof. The sirtuin inhibitors may be used for inhibiting a sirtuin-mediated biological process, and, e.g. for treating and/or preventing diseases and disorders including, but not limited to cancer, neurodegenerative disease and inflammation. Also provided herein are pharmaceutical compositions comprising these sirtuin inhibitors and compositions comprising a sirtuin inhibitor in combination with another therapeutic agent.

  本文提供了新颖的替代噻吩[3,2-d]嘧啶-6-羧酰胺Sirtuin抑制剂及其使用方法。这些Sirtuin抑制剂可用于抑制Sirtuin介导的生物过程，例如用于治疗和/或预防包括但不限于癌症、神经退行性疾病和炎症在内的疾病和疾患。本文还提供了包含这些Sirtuin抑制剂的药物组合物以及包含Sirtuin抑制剂与另一种治疗药剂组合的组合物。
• THIENO[3,2-D]PYRIMIDINE-6-CARBOXAMIDES AND ANALOGUES AS SIRTUIN MODULATORS
  申请人：GLAXOSMITHKLINE LLC

  公开号：US20160002273A1

  公开（公告）日：2016-01-07

  Provided herein are novel substituted thieno[3,2-d]pyrimidine-6-carboxamide sirtuin inhibitors and methods of use thereof. The sirtuin inhibitors may be used for inhibiting a sirtuin-mediated biological process, and, e.g. for treating and/or preventing diseases and disorders including, but not limited to cancer, neurodegenerative disease and inflammation. Also provided herein are pharmaceutical compositions comprising these sirtuin inhibitors and compositions comprising a sirtuin inhibitor in combination with another therapeutic agent.

  本文提供了一种新型的取代噻吩[3,2-d]嘧啶-6-羧酰胺sirtuin抑制剂及其使用方法。这些sirtuin抑制剂可用于抑制sirtuin介导的生物过程，例如用于治疗和/或预防癌症、神经退行性疾病和炎症等疾病和疾患。本文还提供了包含这些sirtuin抑制剂的制药组合物和包含sirtuin抑制剂与另一种治疗剂的组合物。
• Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein–Protein Interaction from Nonselective Fragments
  作者：Markella Konstantinidou、Emira J. Visser、Edmee Vandenboorn、Sheng Chen、Priyadarshini Jaishankar、Maurits Overmans、Shubhankar Dutta、R. Jeffrey Neitz、Adam R. Renslo、Christian Ottmann、Luc Brunsveld、Michelle R. Arkin

  DOI：10.1021/jacs.3c05161

  日期：2023.9.20

  fragment toward selective and highly potent small-molecule stabilizers of the 14-3-3σ/ERα complex. The more elaborated molecular glues, for example, show no stabilization of 14-3-3σ/C-RAF up to 150 μM compound. Orthogonal biophysical assays, including mass spectrometry and fluorescence anisotropy, were used to establish structure–activity relationships. The binding modes of 37 compounds were elucidated

  蛋白质-蛋白质相互作用（PPI）的稳定已成为化学生物学和药物发现领域的一种有前景的策略。确定稳定天然 PPI 的合适起点以及随后将其加工成选择性和有效的分子胶，缺乏结构引导的优化策略。我们之前已经鉴定了一个二硫键片段，该片段可以稳定与几个客户（包括 ERα 和 C-RAF）结合的中心蛋白 14-3-3σ。在这里，我们展示了针对 14-3-3σ/ERα 复合物的选择性和高效小分子稳定剂的非选择性片段的基于结构的优化。例如，更精细的分子胶在高达 150 μM 的化合物中显示出 14-3-3σ/C-RAF 没有稳定性。正交生物物理测定，包括质谱和荧光各向异性，用于建立结构-活性关系。通过X射线晶体学阐明了37种化合物的结合模式，这进一步有助于伴随的结构引导优化。通过靶向 14-3-3σ/ERα 界面中的特定氨基酸并用螺环锁定构象，优化的共价稳定剂181实现了与天然产物 Fusicoccin-A
• Rapid PROTAC Discovery Platform: Nanomole-Scale Array Synthesis and Direct Screening of Reaction Mixtures
  作者：Mateusz P. Plesniak、Emilia K. Taylor、Frederik Eisele、Christopher M. B. K. Kourra、Iacovos N. Michaelides、Alice Oram、Johan Wernevik、Zulma Santisteban Valencia、Hannah Rowbottom、Nadia Mann、Linda Fredlund、Valentyna Pivnytska、Anna Novén、Mohammad Pirmoradian、Thomas Lundbäck、R. Ian Storer、Mariell Pettersson、Gian M. De Donatis、Marie Rehnström

  DOI：10.1021/acsmedchemlett.3c00314

  日期：2023.12.14

  empirical, which requires a significant investment of time and resources. To facilitate rapid hit finding, we developed capabilities for PROTAC parallel synthesis and purification by harnessing an array of preformed E3-ligand-linker intermediates. In the next iteration of this approach, we developed a rapid, nanomole-scale PROTAC synthesis methodology using amide coupling that enables direct screening of

  精确的长度、形状和接头连接点都是设计有效的蛋白水解靶向嵌合体 （PROTAC） 的组成部分。由于这些异双功能降解剂的合成复杂性以及计算建模辅助 PROTAC 设计的难度，对结构-活性关系的探索主要依靠经验进行，这需要投入大量时间和资源。为了促进快速发现苗头化合物，我们利用一系列预制的 E3 配体接头中间体开发了 PROTAC 平行合成和纯化的能力。在该方法的下一次迭代中，我们开发了一种使用酰胺偶联的快速、纳摩尔级 PROTAC 合成方法，该方法能够在基于细胞的降解测定以及 logD 和 EPSA 测量中直接筛选未纯化的反应混合物。这种方法极大地扩展和加速了 PROTAC SAR 勘探（5 天而不是几周），并避免了费力且对溶剂要求高的反应混合物进行纯化，从而使其成为一种经济且更可持续的 PROTAC 苗头化合物发现方法。
• M2 Subtype preferring dibenzodiazepinone-type muscarinic receptor ligands: Effect of chemical homo-dimerization on orthosteric (and allosteric?) binding
  作者：Max Keller、Christian Tränkle、Xueke She、Andrea Pegoli、Günther Bernhardt、Armin Buschauer、Roger W. Read

  DOI：10.1016/j.bmc.2015.01.015

  日期：2015.7

  A series of new dibenzodiazepinone-type muscarinic receptor ligands, including two homo-dimeric compounds, was prepared. Sixteen representative compounds were characterized in equilibrium binding studies with [H-3]N-methylscopolamine ([H-3]NMS) at the muscarinic receptor subtype M-2, and seven selected compounds were additionally investigated at M-1, M-3, M-4 and M-5 with respect to receptor subtype selectivity. The side chain of the known M-2 preferring muscarinic receptor antagonist DIBA was widely varied with respect to chain length and type of the basic group (amine, imidazole, guanidine and piperazine). Most of the structural changes were well tolerated with respect to muscarinic receptor binding, determined by displacement of [H-3]NMS. Compounds investigated at all subtypes shared a similar selectivity profile, which can be summarized as M-2 > M-1 approximate to M-4 > M-3 approximate to M-5 (46, 50, 57, 62-64) and M-2 > M-1 approximate to M-4 > M-3 > M-5 (1, 58). The homo-dimeric dibenzodiazepinone derivatives UNSW-MK250 (63) and UNSW-MK262 (64) exhibited the highest M-2 receptor affinities (pIC(50) = 9.0 and 9.2, respectively). At the M-2 receptor a steep curve slope of -2 was found for the dimeric ligand 63, which cannot be described according to the law of mass action, suggesting a more complex mechanism of binding. In addition to equilibrium binding studies, for selected ligands, we determined pEC(50,diss), an estimate of affinity to the allosteric site of M-2 receptors occupied with [H-3]NMS. Compounds 58 and 62-64 were capable of retarding [H-3]NMS dissociation by a factor > 10 (E-max,E-diss >92%), with highest potency (pEC(50,diss) = 5.56) residing in the dimeric compound 64. As the monomeric counterpart of 64 was 100 times less potent (62: pEC(50),(diss) = 3.59), these data suggest that chemical dimerization of dibenzodiazepinone-type M receptor ligands can enhance allosteric binding. (C) 2015 Elsevier Ltd. All rights reserved.