6-氨基-2-氯烟酸 | 1060811-66-6

• 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
• 中文名称: 6-氨基-2-氯烟酸
• 英文名称: 6-amino-2-chloronicotinic acid
• 英文别名: 6-Amino-2-chloronicotinic acid；6-amino-2-chloropyridine-3-carboxylic acid
• CAS: 1060811-66-6
• 化学式: C₆H₅ClN₂O₂
• 分子量: 172.571
• InChiKey: USUMQEZUENCWOG-UHFFFAOYSA-N

物化性质

• 沸点：
  399.0±42.0 °C(Predicted)
• 密度：
  1.577±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  76.2
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-氨基-2-氯烟酸 在 盐酸 、 硅酸四乙酯 、 三乙酰氧基硼氢化钠 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 溶剂黄146 、 三乙胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 3′-aza-2′-chlorofolic acid
  参考文献：
  名称：

  3'-Aza-2'-[ 18 F]氟叶酸的放射合成和临床前评价：新型叶酸受体靶向PET示踪剂。

  摘要：

  叶酸受体（FR）已被确定为通过正电子发射断层扫描（PET）参与炎症和自身免疫性疾病的癌症和活化巨噬细胞成像的重要靶标。因此，已经通过将放射性标记的辅基与叶酸的谷氨酸部分偶联而合成了叶酸的缀合物（penent方法）。在这项工作中，我们提出了一类新的叶酸，其中叶酸的苯环被吡啶部分等位取代，以便直接用[ 18 F]氟化物标记（整合方法）。在体外对3'-氮杂叶酸及其2'-卤代衍生物（2'-氯和2'-氟）进行了评估，以确定它们的结合亲和力。3'-Aza-2'-[ 18 F]氟叶酸（[ 18 F] 6从N 2-乙酰基-3'-氮杂-2'-氯叶酸二叔丁酯（2）开始，在≥98％的放射化学纯度和高比重下，经最大衰变校正的放射化学收率约为9％。活性为35–127 GBq /μmol。与FR的结合亲和力高（IC 50= 0.8±0.2 nM），并且放射性示踪剂在人体血浆中在37°C下经过4 h稳定。将放射性示踪剂

  DOI：

  10.1021/bc300483a
• 作为产物：
  描述：

  2-氨基-6-氯吡啶 在 N-碘代丁二酰亚胺 、 正丁基锂 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 43.83h， 生成 6-氨基-2-氯烟酸
  参考文献：
  名称：

  Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABAA receptor agonists

  摘要：

  A series of 6-aminonicotinic acid analogues have been synthesized and pharmacologically characterized at native and selected recombinant GABA(A) receptors. 6-Aminonicotinic acid (3) as well as 2- and 4-alkylated analogues (9-11, 14-16) display low to mid-micromolar GABA(A)R binding affinities to native GABA(A) receptors (K(i) 1.1-24 μM). The tetrahydropyridine analogue of 3 (22) shows low-nanomolar affinity (K(i) 0.044 μM) and equipotency as an agonist to GABA itself as well as the standard GABA(A) agonist isoguvacine. Cavities surrounding the core of the GABA binding pocket were predicted by molecular interaction field calculations and docking studies in a α1β2γ2 GABA(A) receptor homology model, and were confirmed by affinities of substituted analogues of 3. The tight steric requirements observed for the remarkably few GABA(A)R agonists reported to date is challenged by our findings. New openings for agonist design are proposed which potentially could facilitate the exploration of different pharmacological profiles within the GABA(A)R area.

  DOI：

  10.1016/j.ejmech.2014.07.039

文献信息

• [EN] 18F-LABELLED FOLATE/ANTIFOLATE ANALOGUES<br/>[FR] ANALOGUES DE FOLATES/ANTIFOLATES MARQUÉS AU 18F
  申请人：MERCK & CIE

  公开号：WO2013167653A1

  公开（公告）日：2013-11-14

  The present invention is directed towards new 18 F- folate/antifolate analogue radiopharmaceuticals, wherein the phenyl group within folate structures has been replaced by an 18F- heterocycle, their precursors, a method of their preparation, as well as their use in diagnosis of a cell or population of cells expressing a folate-receptor and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.

  本发明涉及新的18F-叶酸/抗叶酸类似物放射性药物，其中叶酸结构中的苯基已被18F-杂环取代，其前体物，其制备方法，以及它们在诊断表达叶酸受体的细胞或细胞群以及癌症和炎症性和自身免疫疾病的监测和治疗中的应用。
• 18F-LABELLED FOLATE/ANTIFOLATE ANALOGUES
  申请人：MERCK & CIE

  公开号：US20150125390A1

  公开（公告）日：2015-05-07

  The present invention is directed towards new 18 F-folate/antifolate analogue radiopharmaceuticals, wherein the phenyl group within folate structures has been replaced by an 18 F-heterocycle, their precursors, a method of their preparation, as well as their use in diagnosis of a cell or population of cells expressing a folate-receptor and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.

  本发明涉及新的18F-叶酸类/抗叶酸类模拟放射性药物，其中叶酸结构中的苯基已被18F-杂环取代，其前体，其制备方法，以及它们在诊断表达叶酸受体的细胞或细胞群以及癌症和炎症性和自身免疫疾病的监测和治疗中的应用。
• 18F-labelled folate/antifolate analogues
  申请人：MERCK & CIE

  公开号：US10357576B2

  公开（公告）日：2019-07-23

  The present invention is directed towards new 18F-folate/antifolate analog radiopharmaceuticals, wherein the phenyl group within folate structures has been replaced by an 18F-heterocycle, their precursors, a method of their preparation, as well as their use in diagnosis of a cell or population of cells expressing a folate-receptor and monitoring of cancer and inflammatory and autoimmune diseases and therapy thereof.

  本发明涉及新型 18F 叶酸/抗叶酸类似放射性药物（其中叶酸结构中的苯基已被 18F 异环取代）、其前体、制备方法，以及它们在诊断表达叶酸受体的细胞或细胞群、监测癌症、炎症和自身免疫性疾病及其治疗中的用途。
• Synthesis and pharmacological evaluation of 6-aminonicotinic acid analogues as novel GABAA receptor agonists
  作者：Jette G. Petersen、Troels Sørensen、Maria Damgaard、Birgitte Nielsen、Anders A. Jensen、Thomas Balle、Rikke Bergmann、Bente Frølund

  DOI：10.1016/j.ejmech.2014.07.039

  日期：2014.9

  A series of 6-aminonicotinic acid analogues have been synthesized and pharmacologically characterized at native and selected recombinant GABA(A) receptors. 6-Aminonicotinic acid (3) as well as 2- and 4-alkylated analogues (9-11, 14-16) display low to mid-micromolar GABA(A)R binding affinities to native GABA(A) receptors (K(i) 1.1-24 μM). The tetrahydropyridine analogue of 3 (22) shows low-nanomolar affinity (K(i) 0.044 μM) and equipotency as an agonist to GABA itself as well as the standard GABA(A) agonist isoguvacine. Cavities surrounding the core of the GABA binding pocket were predicted by molecular interaction field calculations and docking studies in a α1β2γ2 GABA(A) receptor homology model, and were confirmed by affinities of substituted analogues of 3. The tight steric requirements observed for the remarkably few GABA(A)R agonists reported to date is challenged by our findings. New openings for agonist design are proposed which potentially could facilitate the exploration of different pharmacological profiles within the GABA(A)R area.
• Radiosynthesis and Preclinical Evaluation of 3′-Aza-2′-[¹⁸F]fluorofolic Acid: A Novel PET Radiotracer for Folate Receptor Targeting
  作者：Thomas Betzel、Cristina Müller、Viola Groehn、Adrienne Müller、Josefine Reber、Cindy R. Fischer、Stefanie D. Krämer、Roger Schibli、Simon M. Ametamey

  DOI：10.1021/bc300483a

  日期：2013.2.20

  where the phenyl ring of folic acid was isosterically replaced by a pyridine moiety for direct labeling with [18F]fluoride (integrated approach). 3′-Azafolic acid and its 2′-halogenated derivatives (2′-chloro and 2′-fluoro) were evaluated in vitro to determine their binding affinity. 3′-Aza-2′-[18F]fluorofolic acid ([18F]6) was obtained, starting from N2-acetyl-3′-aza-2′-chlorofolic acid di-tert-butylester

  叶酸受体（FR）已被确定为通过正电子发射断层扫描（PET）参与炎症和自身免疫性疾病的癌症和活化巨噬细胞成像的重要靶标。因此，已经通过将放射性标记的辅基与叶酸的谷氨酸部分偶联而合成了叶酸的缀合物（penent方法）。在这项工作中，我们提出了一类新的叶酸，其中叶酸的苯环被吡啶部分等位取代，以便直接用[ 18 F]氟化物标记（整合方法）。在体外对3'-氮杂叶酸及其2'-卤代衍生物（2'-氯和2'-氟）进行了评估，以确定它们的结合亲和力。3'-Aza-2'-[ 18 F]氟叶酸（[ 18 F] 6从N 2-乙酰基-3'-氮杂-2'-氯叶酸二叔丁酯（2）开始，在≥98％的放射化学纯度和高比重下，经最大衰变校正的放射化学收率约为9％。活性为35–127 GBq /μmol。与FR的结合亲和力高（IC 50= 0.8±0.2 nM），并且放射性示踪剂在人体血浆中在37°C下经过4 h稳定。将放射性示踪剂