6-氨基-5-氧代-1,2,3,5-四氢-8-吲嗪羧酸 | 185856-19-3

• 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-5-氧代-1,2,3,5-四氢-8-吲嗪羧酸
• 英文名称: 6-Amino-5-oxo-1,2,3,5-tetrahydro-indolizine-8-carboxylic acid
• 英文别名: 6-Amino-5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylic acid；6-amino-5-oxo-2,3-dihydro-1H-indolizine-8-carboxylic acid
• CAS: 185856-19-3
• 化学式: C₉H₁₀N₂O₃
• 分子量: 194.19
• InChiKey: XSCBIVUGSMDBOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  83.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  甲胺 、 6-氨基-5-氧代-1,2,3,5-四氢-8-吲嗪羧酸 在 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以57%的产率得到6-amino-N-methyl-5-oxo-2,3-dihydro-1H-indolizine-8-carboxamide
  参考文献：
  名称：

  [EN] CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS
  [FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE COMME INHIBITEURS DE NIK

  摘要：

  融合的芳香族双环取代5-(2-氨基-4-嘧啶基)-氰基吲哚衍生物（I）用于哺乳动物的治疗和/或预防，特别是用于抑制NF-KB诱导激酶（NIK - 也称为MAP3K14）的抑制剂，用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病的代谢性疾病和自身免疫性疾病。

  公开号：

  WO2018002219A1
• 作为产物：
  描述：

  methyl α-(tetrahydro-2-pyrrolidinylidene)acetate 在 bismuth (III) nitrate pentahydrate 、 水 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 0.42h， 生成 6-氨基-5-氧代-1,2,3,5-四氢-8-吲嗪羧酸
  参考文献：
  名称：

  [EN] CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS
  [FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE COMME INHIBITEURS DE NIK

  摘要：

  融合的芳香族双环取代5-(2-氨基-4-嘧啶基)-氰基吲哚衍生物（I）用于哺乳动物的治疗和/或预防，特别是用于抑制NF-KB诱导激酶（NIK - 也称为MAP3K14）的抑制剂，用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病的代谢性疾病和自身免疫性疾病。

  公开号：

  WO2018002219A1

文献信息

• Cyanoindoline derivatives as NIK inhibitors
  申请人：Janssen Pharmaceutica NV

  公开号：US11186589B2

  公开（公告）日：2021-11-30

  The present invention relates to pharmaceutical agents useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-κB-inducing kinase (NIK—also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  本发明涉及可用于哺乳动物治疗和/或预防的药物制剂，尤其涉及可用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病等疾病的NF-κB诱导激酶（NIK-又称MAP3K14）抑制剂。本发明还涉及包含此类化合物的药物组合物，以及使用此类化合物或药物组合物预防或治疗癌症、炎症性疾病、代谢紊乱（包括肥胖和糖尿病）和自身免疫性疾病等疾病。
• Formation of Dihydropyridone- and Pyridone-Based Peptide Analogs through Aza-Annulation of β-Enamino Ester and Amide Substrates with α-Amido Acrylate Derivatives
  作者：Lars G. Beholz、Petr Benovsky、Donald L. Ward、Nancy S. Barta、John R. Stille

  DOI：10.1021/jo9600520

  日期：1997.2.1

  The aza-annulation of beta-enamino ester and amide substrates with the mixed anhydride of 2-acetamidoacrylic acid was used for the efficient construction of highly substituted alpha-acetamido delta-lactam products. With the alpha-acetamido substituent, lactam functionality, and gamma-carboxylate group, these delta-lactam products represent an interesting class of conformationally restricted dipeptide analogs. The framework of this lactam hub is structurally related to that of an alpha-amino acid coupled with a beta-amino acid. When alpha-amino esters derived from naturally occurring amino acids were used in the enamine formation step, subsequent aza-annulation led to branched peptide surrogates with two C-termini that extended from a common N-terminus. Oxidation of the aza-annulation products resulted in the generation of a planar system with peptide functionality radiating from the 1, 3, and 5 positions of the pyridone hub. Alternatively, pyridone products could be formed directly from the enamino amides by reaction with 2-phenyl-4-(ethoxymethylene)oxazolone. Subsequent hydrolysis of the acetamido and ester substituents of the N-benzylpyridones was selectively performed to access unique beta-amino acid products. Formation of the mixed anhydride of this acid, followed by amide bond formation with the ester of an alpha-amino acid, allowed extension of the peptide chain from the dihydropyridone structure.
• CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS
  申请人：Janssen Pharmaceutica NV

  公开号：EP3478673B1

  公开（公告）日：2020-09-16
• [EN] CYANOINDOLINE DERIVATIVES AS NIK INHIBITORS<br/>[FR] NOUVEAUX DÉRIVÉS DE CYANOINDOLINE COMME INHIBITEURS DE NIK
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2018002219A1

  公开（公告）日：2018-01-04

  Fused aromatic bicyclic substituted 5-(2-amino-4-pyrimidinyl)- cyanoindoline derivatives (I) useful for therapy and/or prophylaxis in a mammal, and in particular to inhibitors of NF-KB-inducing kinase (NIK - also known as MAP3K14) useful for treating diseases such as cancer, inflammatory disorders, metabolic disorders and autoimmune disorders. The invention is also directed to pharmaceutical compositions comprising such compounds, and to the use of such compounds or pharmaceutical compositions for the prevention or treatment of diseases such as cancer, inflammatory disorders, metabolic disorders including obesity and diabetes, and autoimmune disorders.

  融合的芳香族双环取代5-(2-氨基-4-嘧啶基)-氰基吲哚衍生物（I）用于哺乳动物的治疗和/或预防，特别是用于抑制NF-KB诱导激酶（NIK - 也称为MAP3K14）的抑制剂，用于治疗癌症、炎症性疾病、代谢性疾病和自身免疫性疾病。本发明还涉及包含这些化合物的药物组合物，以及使用这些化合物或药物组合物预防或治疗癌症、炎症性疾病、包括肥胖和糖尿病的代谢性疾病和自身免疫性疾病。