2,5-dioxopyrrolidin-1-yl picolinate | 83039-59-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2,5-dioxopyrrolidin-1-yl picolinate
• 英文别名: (2,5-dioxopyrrolidin-1-yl) pyridine-2-carboxylate；1-[(2-Pyridinylcarbonyl)oxy]-2,5-pyrrolidinedione
• CAS: 83039-59-2
• 化学式: C₁₀H₈N₂O₄
• mdl: MFCD02916458
• 分子量: 220.185
• InChiKey: PEYUFPYVQJYKPV-UHFFFAOYSA-N

物化性质

• 沸点：
  370.3±34.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  76.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,5-dioxopyrrolidin-1-yl picolinate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 氯仿 、 水 、 乙腈 为溶剂， 反应 6.0h， 生成 N-(2’-吡啶甲酰基)哌嗪
  参考文献：
  名称：

  Structure–Activity Relationships of Potent, Targeted Covalent Inhibitors That Abolish Both the Transamidation and GTP Binding Activities of Human Tissue Transglutaminase

  摘要：

  Human tissue transglutaminase (hTG2) is a multifunctional enzyme. It is primarily known for its calcium dependent transamidation activity that leads to formation of an isopeptide bond between glutamine and lysine residues found on the surface of proteins, but it is also a GTP binding protein. Overexpression and unregulated hTG2 activity have been associated with numerous human diseases, including cancer stem cell survival and metastatic phenotype. Herein, we present a series of targeted covalent inhibitors (TCIs) based on our previously reported Cbz-Lys scaffold. From this structure activity relationship (SAR) study, novel irreversible inhibitors were identified that block the transamidation activity of hTG2 and allosterically abolish its GTP binding ability with a high degree of selectivity and efficiency (k(inact)/K-I > 10(5) M-1 min(-1)). One optimized inhibitor (VA4) was also shown to inhibit epidermal cancer stem cell invasion with an EC50 of 3.9 mu M, representing a significant improvement over our previously reported "hit" NC9.

  DOI：

  10.1021/acs.jmedchem.7b01070
• 作为产物：
  描述：

  2-吡啶甲酸 在 氯化亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 2,5-dioxopyrrolidin-1-yl picolinate
  参考文献：
  名称：

  一种合成异烟酸和吡啶甲酸活性酯的简单方法

  摘要：

  报道了从相应的酸制备异烟酸和吡啶甲酸的对硝基苯基-、N-羟基琥珀酰亚胺基-和五氟苯基酯的方法。

  DOI：

  10.3390/60100047

文献信息

• [EN] CHEMOSELECTIVE SENSITIVITY BOOSTER FOR TAGGING A PEPTIDE, PEPTIDE CONJUGATE, OR SIMILAR REACTIVE MOLECULE<br/>[FR] AMPLIFICATEUR DE SENSIBILITÉ CHIMIOSÉLECTIF POUR MARQUER UN PEPTIDE, UN CONJUGUÉ PEPTIDIQUE OU UNE MOLÉCULE RÉACTIVE SIMILAIRE
  申请人：INDIAN INSTITUTE OF SCIENCE EDUCATION AND RES BHOPAL

  公开号：WO2020245843A1

  公开（公告）日：2020-12-10

  The invention pertains to chemoselective sensitivity booster for tagging a peptide, peptide conjugate, or similar reactive molecule for analysis of a peptide, protein, antibody, protein bioconjugate, antibody bioconjugate, and similar analytes. The sensitivity booster comprises of sp2 or sp3 nitrogen centers in combination with hydrophobic carbon chains linked with an electrophile or nucleophile for attachment with a peptide, peptide conjugate, or molecules with similar reactivity.

  这项发明涉及一种化学选择性增敏剂，用于标记肽、肽共轭物或类似的反应分子，以便分析肽、蛋白质、抗体、蛋白生物共轭物、抗体生物共轭物和类似的分析物。该增敏剂包括与亲水碳链结合的sp2或sp3氮中心，与带有亲电子或亲核子的肽、肽共轭物或具有类似反应性的分子结合。
• Preparation of Deuterated Methyl and Dimethyl Substituted Nicotinoylating Agents for Derivatization of the N-Terminal of Protein
  作者：Hiroki Tsumoto、Chie Murata、Naoki Miyata、Ryo Taguchi、Kohfuku Kohda

  DOI：10.1248/cpb.51.1399

  日期：——

  Methyl groups of 6-methylnicotinic acid and 2,6-dimethylnicotinic acid were deuterated by an H-D exchange reaction under conditions of 1% NaOD/D(2)O on heating. With a condensation reaction between the D-labeled nicotinic acid derivative and N-hydroxysuccinimide with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, the nicotinoylating agents, 1-(6-methyl[D(3)]nicotinoyloxy)succinimide (2c)

  在1％NaOD / D（2）O的加热条件下，通过HD交换反应使6-甲基烟酸和2,6-二甲基烟酸的甲基氘化。通过D-标记的烟酸衍生物和N-羟基琥珀酰亚胺与1-乙基-3-（3-二甲基氨基丙基）碳二亚胺盐酸盐的缩合反应，烟酰化剂1-（6-甲基[D（3）]烟酰氧基）琥珀酰亚胺制备（2c）和1-（2,6-二甲基[D（6）]烟酰氧基）琥珀酰亚胺（2f）。D标记的烟酰化剂及其未标记的对应物均定量修饰了蛋白质的N端。
• Synthesis and biological evaluation of a new class of triazin–triazoles as potential inhibitors of human farnesyltransferase
  作者：Liliana Lucescu、Elena Bîcu、Dalila Belei、Sergiu Shova、Benoît Rigo、Philippe Gautret、Joëlle Dubois、Alina Ghinet

  DOI：10.1007/s11164-015-2131-1

  日期：2016.3

  A new synthesis of ethynyldimethoxytriazine 1, an important platform-compound for developing new chemical entities for anticancer research and for other biological applications, is described. Compound 1 was further reacted with azides 5a–i to provide triazin–triazoles 2a–i, which were tested on human farnesyltransferase and on the NCI-60 human tumor cell lines. Synthesis of other dimethoxytriazine derivatives 15 and 16, linked to a sp 2 or a sp 3 carbon atom were also studied.

  报道了一种新型乙炔基二甲氧基三嗪1的合成方法，该化合物是开发抗癌研究和其他生物应用中新型化学实体的重要平台化合物。化合物1进一步与叠氮化合物5a–i反应，得到了三嗪-三唑2a–i，并对其在人体法呢基转移酶和NCI-60人体肿瘤细胞系中的活性进行了测试。同时，还研究了其他连接于sp2或sp3碳原子的二甲氧基三嗪衍生物15和16的合成。
• [EN] NEW TRIFLUOROMETHYLPROPANAMIDE DERIVATIVES AS HTRA1 INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE TRIFLUOROMÉTHYLPROPANAMIDE UTILISÉS COMME INHIBITEURS DE HTRA1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2017148964A1

  公开（公告）日：2017-09-08

  The invention provides serine protease HTRA1 inhibiting compounds having the general formula (I) wherein R 2, R 3, R 4, R 5, R 6, R 7, R 3, R 8, R 10, R 11and R 23 are as described herein. These compounds are suitable for the treatment of ocular diseases such as age-related macular degeneration and others.

  这项发明提供了一种通式（I）的丝氨酸蛋白酶HTRA1抑制化合物，其中R2、R3、R4、R5、R6、R7、R3、R8、R10、R11和R23如本文所述。这些化合物适用于治疗眼部疾病，如年龄相关性黄斑变性等。
• Chemistry of Bifunctional Photoprobes. 6. Synthesis and Characterization of High Specific Activity Metalated Photochemical Probes: Development of Novel Rhenium Photoconjugates of Human Serum Albumin and Fab Fragments
  作者：Raghavan Rajagopalan、Robert R. Kuntz、Uday Sharma、Wynn A. Volkert、Raghoottama S. Pandurangi

  DOI：10.1021/jo010782u

  日期：2002.9.1

  Functionalization of perfluoro aryl azides by bifunctional chelating agents (BFCAs) capable of forming high specific activity complexes with (99m)Tc (for gamma-imaging) and (188)Re (for radiotherapy) is described. The synthesis of multidonor BFCAs containing N(2)S(2), N(4), and N(3)S donor groups containing imidazole, pyridine, and pyrazine functionalities that may be important for tuning the pharmacokinetic

  描述了双官能螯合剂（BFCA）对全氟芳基叠氮化物的官能化，该双官能螯合剂能够与（99m）Tc（对于γ成像）和（188）Re（对于放射疗法）形成高比活络合物。还介绍了含有N（2）S（2），N（4）和N（3）S供体基团的多供体BFCA的合成，该供体基团对调节药代动力学参数可能很重要，其中包括咪唑，吡啶和吡嗪官能团。全氟芳基叠氮化物在BFCA上各个位置的功能化产生了新型的双功能光不稳定螯合剂（BFPCA），可用于共价连接生物分子。在模型溶剂二乙胺中的代表性Re-BFPCA 8a可以在不使8a的金属离子分解的情况下，获得高产率的分子间NH插入产物。通过分析技术对所有源自8a在二乙胺中的光解产物进行了表征，并提出了形成不同光解产物的合理机制。Re-BFPCA 8a分子间NH插入的高产率扩展到在水性条件下标记人血清白蛋白（HSA）和Fab片段。此处开发的光标记技术提供了一种新方法，可将诊断和治疗上有用