丁酸,3-[[[(1S,9S)-八氢-9-[(1-异喹啉基羰基)氨基]-6,10-二羰基-6H-吡啶联氮基[1,2-a][1,2]重氮基庚英-1-基]羰基]氨基]-4-羰基-,(3S)- | 192756-07-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: 丁酸,3-[[[(1S,9S)-八氢-9-[(1-异喹啉基羰基)氨基]-6,10-二羰基-6H-吡啶联氮基[1,2-a][1,2]重氮基庚英-1-基]羰基]氨基]-4-羰基-,(3S)-
• 英文名称: pralnacasan
• 英文别名: VRT-18858；WV88DU3Mux；(3S)-3-[[(4S,7S)-7-(isoquinoline-1-carbonylamino)-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carbonyl]amino]-4-oxobutanoic acid
• CAS: 192756-07-3
• 化学式: C₂₄H₂₅N₅O₇
• 分子量: 495.492
• InChiKey: CUVNEENHHCPUBW-SZMVWBNQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  166
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (1S,9S)-9-(1,3-dioxoisoindolin-2-yl)-6,10-dioxooctahydro-1H-pyridazino[1,2-a][1,2]diazepine-1-carboxylic acid 在 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.34h， 生成 丁酸,3-[[[(1S,9S)-八氢-9-[(1-异喹啉基羰基)氨基]-6,10-二羰基-6H-吡啶联氮基[1,2-a][1,2]重氮基庚英-1-基]羰基]氨基]-4-羰基-,(3S)-
  参考文献：
  名称：

  由无铜菌株促进的炔-叠氮化物环加成（SPAAC）组装的熔融双环Caspase-1抑制剂

  摘要：

  开发针对caspase-1的有效和选择性小分子抑制剂时面临着挑战。在此，通过利用二氟环辛炔（DIFO）与各种含叠氮化合物之间的无铜应变促进炔-叠氮环加成（SPAAC）反应，我们首次证明了可以快速合成潜在的胱天蛋白酶-1抑制剂。生成的稠合双环化合物在结构上类似于Pralnacasan（一种著名的小分子caspase-1抑制剂）的中心部分（P 2 –P 3），在P 4处具有多样性。可以从叠氮化物组件方便地安装的亲本抑制剂的位置。由于我们的SPAAC组装的抑制剂库是使用无铜生物正交化学方法合成的，因此所得的52个成员的库（2个DIFOs×26个叠氮化物）可立即用于随后的基于细胞的筛选，以快速鉴定潜在的可渗透细胞的能力有效抑制内源性caspase-1活性的方法。C1FS是一种最近报道的荧光双光子探针，具有提高的活细胞对内源性caspase-1的成像敏感性，已在体外和LPS / ATP诱导的巨噬细胞

  DOI：

  10.1002/chem.201603150

文献信息

• Inhibitors of interleukin-1beta converting enzyme
  申请人：Batchelor James Mark

  公开号：US20080039449A1

  公开（公告）日：2008-02-14

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-γ-mediated diseases and decreasing IGIF and IFN-γ production using the compounds and compositions of this invention. This invention also relates to methods for preparing-N-acylamino compounds.

  本发明涉及一种新型的化合物类别，其为白细胞介素-1β转化酶的抑制剂。本发明的ICE抑制剂具有特定的结构和物理化学特征。本发明还涉及包含这些化合物的制药组合物。本发明的化合物和制药组合物特别适用于抑制ICE活性，因此可以作为抗IL-1、凋亡、IGIF、IFN-γ介导的疾病、炎症性疾病、自身免疫性疾病、破坏性骨病、增生性疾病、感染性疾病、退行性疾病和坏死性疾病的药物。本发明还涉及使用这些化合物和组合物抑制ICE活性、治疗白细胞介素-1、凋亡、IGIF和IFN-γ介导的疾病、降低IGIF和IFN-γ的产生的方法。本发明还涉及制备N-酰基氨基化合物的方法。
• INHIBITORS OF INTERLEUKIN-1 BETA CONVERTING ENZYME
  申请人：Batchelor Mark James

  公开号：US20110178069A1

  公开（公告）日：2011-07-21

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physicochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF- and IFN-γ-mediated diseases and decreasing IGIF and IFN-γ production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

  本发明涉及一种新型化合物类别，其为白细胞介素-1β转化酶抑制剂。本发明的ICE抑制剂具有特定的结构和物理化学特征。本发明还涉及包含这些化合物的制药组合物。本发明的化合物和制药组合物特别适用于抑制ICE活性，因此可以优势地用作对抗IL-1、凋亡、IGIF和IFN-γ介导的疾病、炎症性疾病、自身免疫性疾病、破坏性骨病、增生性疾病、传染性疾病、退行性疾病和坏死性疾病的药剂。本发明还涉及使用本发明的化合物和组合物抑制ICE活性、治疗白细胞介素-1、凋亡、IGIF和IFN-γ介导的疾病、减少IGIF和IFN-γ产生的方法。本发明还涉及制备N-酰基氨基化合物的方法。
• Inhibitors of interleukin-1ß converting enzyme
  申请人：Vertex Pharmceuticals Incorporated

  公开号：EP2083014A2

  公开（公告）日：2009-07-29

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1β converting enzyme. The ICE inhibitors of this invention are characterized by specific structural and physiochemical features. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting ICE activity and consequently, may be advantageously used as agents against IL-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases, inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, degenerative diseases, and necrotic diseases. This invention also relates to methods for inhibiting ICE activity, for treating interleukin-1-, apoptosis-, IGIF-, and IFN-γ-mediated diseases and decreasing IGIF, and IFN-γ production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

  本发明涉及一类新型化合物，它们是白细胞介素-1β转换酶的抑制剂。本发明的 ICE 抑制剂具有特定的结构和理化特征。本发明还涉及包含这些化合物的药物组合物。本发明的化合物和药物组合物特别适用于抑制 ICE 的活性，因此可作为抗 IL-1、细胞凋亡、IGIF 和 IFN-γ 介导的疾病、炎症性疾病、自身免疫性疾病、破坏性骨疾病、增殖性疾病、感染性疾病、退行性疾病和坏死性疾病的药物。本发明还涉及使用本发明化合物和组合物抑制 ICE 活性、治疗白细胞介素-1、细胞凋亡、IGIF 和 IFN-γ 介导的疾病以及减少 IGIF 和 IFN-γ 生成的方法。本发明还涉及制备 N-酰氨基化合物的方法。
• EXTENDED RELEASE FORMULATION FOR PRALNACASAN
  申请人：SOENNICHSEN Caren

  公开号：US20080279934A1

  公开（公告）日：2008-11-13

  This invention relates to a sustained release tablet comprising at least two layers, wherein at least one layer rapidly releases pralnacasan and the other layer releases pralnacasan in a delayed manner. This tablet is particularly suitable for the treatment of a condition such as autoimmune diseases, type I and type II diabetes, rheumatoid arthritis, osteoarthritis or psoriasis.
• TREATING SEIZURES USING ICE INHIBITORS
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US20150190404A1

  公开（公告）日：2015-07-09

  This invention relates to methods and compositions for treating or preventing seizures.