乙基2-(3-甲基-4-氧亚基-3,4-二氢酞嗪-1-基)醋酸盐 | 356790-62-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 乙基2-(3-甲基-4-氧亚基-3,4-二氢酞嗪-1-基)醋酸盐
• 英文名称: ethyl 2-(3-methyl-4-oxo-3,4-dihydrophthalazin-1-yl)acetate
• 英文别名: ethyl 2-(3-methyl-4-oxophthalazin-1-yl)acetate
• CAS: 356790-62-0
• 化学式: C₁₃H₁₄N₂O₃
• 分子量: 246.266
• InChiKey: MOQFTWAPXKWBLW-UHFFFAOYSA-N

物化性质

• 沸点：
  387.6±44.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙基2-(3-甲基-4-氧亚基-3,4-二氢酞嗪-1-基)醋酸盐 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 (3-甲基-4-氧代-3,4-二氢-1-酞嗪)乙酸
  参考文献：
  名称：

  Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum

  摘要：

  Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C parvum infection is also presented. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.12.037
• 作为产物：
  描述：

  ethyl [(E)-3-oxo-1,3-dihydroisobenzofuran-1-ylidene]acetate 在 potassium carbonate 、 肼 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 乙基2-(3-甲基-4-氧亚基-3,4-二氢酞嗪-1-基)醋酸盐
  参考文献：
  名称：

  [EN] NOVEL IL-2/IL-15 RECEPTOR ANTAGONIST COMPOUNDS AND USES THEREOF FOR THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES OR GRAFT REJECTION
  [FR] NOUVEAUX COMPOSÉS ANTAGONISTES DES RÉCEPTEURS DE L'IL-2/IL-15 ET LEURS UTILISATIONS POUR LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET INFLAMMATOIRES OU DU REJET DE GREFFE

  摘要：

  新型IL-2/IL-15受体拮抗剂化合物及其用于治疗自身免疫和炎症性疾病或移植排斥的用途。该发明涉及一般式（1）的化合物，其中X代表O、S或NR4，其中R4为烷基；A从S、SO、SO2、NH和O中选择；Y代表（CR5R6）n或（CR5 R6 O）n，其中R5和R6相同或不同为H或烷基，n表示1至15的整数；R1代表5至10成员芳香或非芳香单环或双环，1可选择桥接环，R2为C1-C4烷基；R3为H或烷基；p为0或1；或其药学上可接受的盐。该发明的化合物是IL-2/15与IL-2/15Rβ相互作用的抑制剂，因此在治疗自身免疫或炎症性疾病和移植排斥方面有用。

  公开号：

  WO2015181394A1

文献信息

• [EN] NOVEL IL-2/IL-15 RECEPTOR ANTAGONIST COMPOUNDS AND USES THEREOF FOR THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES OR GRAFT REJECTION<br/>[FR] NOUVEAUX COMPOSÉS ANTAGONISTES DES RÉCEPTEURS DE L'IL-2/IL-15 ET LEURS UTILISATIONS POUR LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET INFLAMMATOIRES OU DU REJET DE GREFFE
  申请人：INSERM INST NAT DE LA SANTÉ ET DE LA RECH MÉDICALE

  公开号：WO2015181394A1

  公开（公告）日：2015-12-03

  Novel IL-2/IL-15 Receptor antagonist compounds and uses thereof for the treatment of autoimmune and inflammatory diseases or graft rejection Novel IL-2/IL-15 Receptor antagonist compounds and uses thereof for the treatment of autoimmune and inflammatory diseases or graft rejection. The invention relates to a compound of general formula (1) wherein X represents O, S or NR 4, wherein R4 is alkyl; A is selected from S, SO, SO2, NH and O; Y represents (CR5R6)n or (CR5 R6 O)n, wherein R5 and R6 identical or different are H or alkyl and n represents an integer from 1 to 15; R1 represents a 5 to 10 membered aromatic or non-aromatic mono-or bicyclic, 1 optionally bridged ring, R2 is C1-C4 alkyl; R3 is H or alkyl; p is 0 or 1; or a pharmaceutically acceptable salt thereof. The compounds of the invention are inhibitors of the interactions of IL-2/15 to IL-2/15Rβand hence useful in the treatment of an autoimmune or an inflammatory diseases and graft rejection.

  新型IL-2/IL-15受体拮抗剂化合物及其用于治疗自身免疫和炎症性疾病或移植排斥的用途。该发明涉及一般式（1）的化合物，其中X代表O、S或NR4，其中R4为烷基；A从S、SO、SO2、NH和O中选择；Y代表（CR5R6）n或（CR5 R6 O）n，其中R5和R6相同或不同为H或烷基，n表示1至15的整数；R1代表5至10成员芳香或非芳香单环或双环，1可选择桥接环，R2为C1-C4烷基；R3为H或烷基；p为0或1；或其药学上可接受的盐。该发明的化合物是IL-2/15与IL-2/15Rβ相互作用的抑制剂，因此在治疗自身免疫或炎症性疾病和移植排斥方面有用。
• COMPOUNDS AND METHODS FOR TREATING MAMMALIAN GASTROINTESTINAL MICROBIAL INFECTIONS
  申请人：Brandeis University

  公开号：US20150210727A1

  公开（公告）日：2015-07-30

  Disclosed are compounds and pharmaceutically acceptable salts thereof, which are useful as inhibitors of IMPDH. In certain embodiments, a compound selectively inhibits a parasitic IMPDH versus a host IMPDH. Also disclosed are pharmaceutical compositions comprising one or more compounds of the invention. Related methods of treating various parasitic and bacterial infections in mammals are disclosed. Moreover, the compounds may be used alone or in combination with other therapeutic or prophylactic agents, such as anti-virals, anti-inflammatory agents, antimicrobials and immunosuppressants.

  本发明公开了一种化合物及其药学上可接受的盐，它们可用作IMPDH的抑制剂。在某些实施例中，该化合物选择性地抑制寄生IMPDH而不影响宿主IMPDH。本发明还公开了包含本发明中一种或多种化合物的制药组合物。公开了治疗哺乳动物中各种寄生虫和细菌感染的相关方法。此外，这些化合物可单独或与其他治疗或预防药物，如抗病毒药物、抗炎药物、抗微生物药物和免疫抑制剂一起使用。
• Phthalazinone inhibitors of inosine-5′-monophosphate dehydrogenase from Cryptosporidium parvum
  作者：Corey R. Johnson、Suresh Kumar Gorla、Mandapati Kavitha、Minjia Zhang、Xiaoping Liu、Boris Striepen、Jan R. Mead、Gregory D. Cuny、Lizbeth Hedstrom

  DOI：10.1016/j.bmcl.2012.12.037

  日期：2013.2

  Cryptosporidium parvum (Cp) is a potential biowarfare agent and major cause of diarrhea and malnutrition. This protozoan parasite relies on inosine 5'-monophosphate dehydrogenase (IMPDH) for the production of guanine nucleotides. A CpIMPDH-selective N-aryl-3,4-dihydro-3-methyl-4-oxo-1-phthalazineacetamide inhibitor was previously identified in a high throughput screening campaign. Herein we report a structure-activity relationship study for the phthalazinone-based series that resulted in the discovery of benzofuranamide analogs that exhibit low nanomolar inhibition of CpIMPDH. In addition, the antiparasitic activity of select analogs in a Toxoplasma gondii model of C parvum infection is also presented. (C) 2012 Elsevier Ltd. All rights reserved.
• [EN] COMPOUNDS AND METHODS FOR TREATING MAMMALIAN GASTROINTESTINAL MICROBIAL INFECTIONS<br/>[FR] COMPOSÉS ET PROCÉDÉS DE TRAITEMENT D'INFECTIONS MICROBIENNES GASTRO-INTESTINALES DE MAMMIFÈRE
  申请人：UNIV BRANDEIS

  公开号：WO2014028931A3

  公开（公告）日：2014-10-09
• US9447134B2
  申请人：——

  公开号：US9447134B2

  公开（公告）日：2016-09-20