9(S)-benzoylamino-octahydro-6,10-dioxo-6H-pyridazino[1,2-a][1,2]diazepine-1(S)-carboxylic acid | 192753-57-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 9(S)-benzoylamino-octahydro-6,10-dioxo-6H-pyridazino[1,2-a][1,2]diazepine-1(S)-carboxylic acid
• 英文别名: (4S,7S)-7-benzamido-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carboxylic acid
• CAS: 192753-57-4
• 化学式: C₁₇H₁₉N₃O₅
• 分子量: 345.355
• InChiKey: QTUVPJHYTLMQDB-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9(S)-benzoylamino-octahydro-6,10-dioxo-6H-pyridazino[1,2-a][1,2]diazepine-1(S)-carboxylic acid 在 lithium aluminium tetrahydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 为溶剂， 生成 tert-butyl (3S)-3-[[(4S,7S)-7-benzamido-6,10-dioxo-2,3,4,7,8,9-hexahydro-1H-pyridazino[1,2-a]diazepine-4-carbonyl]amino]-4-oxobutanoate
  参考文献：
  名称：

  An efficient stereoselective synthesis of [3S(1S,9S)]-3-[[[9-(benzoylamino)octahydro-6,10-dioxo-6H-pyridazino-(1,2-a)(1,2)-diazepin-1-yl]-carbonyl]amino]-4-oxobutanoic acid, an interleukin converting enzyme (ICE) inhibitor

  摘要：

  The title compound 1 is a potent interleukin-1 beta-converting enzyme (ICE) inhibitor. Recently, an efficient chiral synthesis of compound 1 has been accomplished in our labs. The overall yield of this 18-step stereoselective synthesis was 9.8%. (C) 1999 Elsevier Science Ltd. Ail rights reserved.

  DOI：

  10.1016/s0960-894x(99)00236-x
• 作为产物：
  描述：

  5-溴戊酰氯 在 palladium on activated charcoal N-乙基吗啉 、 N,N-二甲基丙烯基脲 、 lithium hydroxide 、 sodium hydroxide 、 正丁基锂 、 五氯化磷 、 硫酸 、 氢气 、 四丁基碘化铵 、 碳酸氢钠 、 三氟乙酸 、 肼 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 9(S)-benzoylamino-octahydro-6,10-dioxo-6H-pyridazino[1,2-a][1,2]diazepine-1(S)-carboxylic acid
  参考文献：
  名称：

  An efficient stereoselective synthesis of [3S(1S,9S)]-3-[[[9-(benzoylamino)octahydro-6,10-dioxo-6H-pyridazino-(1,2-a)(1,2)-diazepin-1-yl]-carbonyl]amino]-4-oxobutanoic acid, an interleukin converting enzyme (ICE) inhibitor

  摘要：

  The title compound 1 is a potent interleukin-1 beta-converting enzyme (ICE) inhibitor. Recently, an efficient chiral synthesis of compound 1 has been accomplished in our labs. The overall yield of this 18-step stereoselective synthesis was 9.8%. (C) 1999 Elsevier Science Ltd. Ail rights reserved.

  DOI：

  10.1016/s0960-894x(99)00236-x

文献信息

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

  公开号：US20050143436A1

  公开（公告）日：2005-06-30

  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.

  本发明涉及一类新型化合物，这些化合物是白细胞介素-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活性，因此可以有利地用作对抗IL-1、凋亡、IGIF和IFN-γ介导的疾病、炎症性疾病、自身免疫疾病、破坏性骨疾病、增生性疾病、传染性疾病、退行性疾病和坏死性疾病的药剂。本发明还涉及抑制ICE活性的方法，用于治疗白细胞介素-1、凋亡、IGIF和IFN-γ介导的疾病，以及使用本发明的化合物和组合物减少IGIF和IFN-γ的产生的方法。本发明还涉及制备N-酰氨基化合物的方法。
• Carboxamide diazepin derivatives, preparation method, use as medicines, pharmaceutical compositions and use thereof
  申请人：——

  公开号：US20030100550A1

  公开（公告）日：2003-05-29

  The invention concerns products of formula (I) wherein: R 1 represents in particular —C(O)—R5, —SO2—R5 or —C(O)—NR6R5, R2 and R7 are such that either R7 represents a hydrogen atom and R2 is such that the group (a) represents the radical of a natural or non-natural amino acid, or R2 and R7 form together a cycle with the nitrogen and carbon atom whereto they are bound, R3 represents in particular the radical —CH═N2 or —CH2-L—R4, R4 represents in particular a linear or branched alkyl radical, and their additive salts with mineral or organic acids or with mineral or organic bases of said products of formula (I). The invention also concerns the method for preparing said products and their use as medicines.

  该发明涉及公式（I）的产品，其中：R1特别表示—C(O)—R5，—SO2—R5或—C(O)—NR6R5，R2和R7是这样的，要么R7表示氢原子，而R2是这样的，该组（a）代表天然或非天然氨基酸的基团，要么R2和R7共同形成一个环，其中它们与氮和碳原子结合，R3特别表示基团—CH═N2或—CH2-L—R4，R4特别表示线性或支链烷基基团，以及它们与矿物酸或有机酸的加成盐或与矿物碱或有机碱的产品的有机盐的产品（I）的方法。该发明还涉及制备所述产品的方法以及它们作为药物的用途。
• Inhibitors of interleukin-1.beta. converting enzyme
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US06008217A1

  公开（公告）日：1999-12-28

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1.beta. 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 an IL-1 mediated disease, an apoptosis mediated disease, AML, CML, melanoma, myeloma, Kaposi's sarcoma, graft vs host disease, rheumatoid arthritis, inflammatory bowel disorder, psoriasis, osteoarthritis, myeloma, apoptosis, sepsis, rheumatoid arthritis, asthma, Alzheimer's disease, Parkinson's disease, and ischemic heart disease diseases. This invention also relates to methods for inhibiting ICE activity and methods for treating interleukin-1 mediated diseases using the compounds and compositions of this invention.

  本发明涉及一种新型化合物类，其为白细胞介素-1β转化酶的抑制剂。本发明中的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非常适合用作抑制ICE活性的药物，并因此可以作为对抗IL-1介导的疾病、凋亡介导的疾病、AML、CML、黑色素瘤、骨髓瘤、卡波西肉瘤、移植物抗宿主病、类风湿性关节炎、炎症性肠病、牛皮癣、骨关节炎、骨髓瘤、凋亡、败血症、类风湿性关节炎、哮喘、阿尔茨海默病、帕金森病和缺血性心脏病等疾病的药物。本发明还涉及使用这些化合物和组合物抑制ICE活性以及治疗IL-1介导的疾病的方法。
• Inhibitors of interleukin-1&bgr; converting enzyme
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US06423840B1

  公开（公告）日：2002-07-23

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-1&bgr; 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-&ggr;-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-&ggr;-mediated diseases and decreasing IGIF and IFN-&ggr; production using the compounds and compositions of this invention. This invention also relates to methods for preparing N-acylamino compounds.

  本发明涉及一类新的化合物，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，因此可能有利用作为IL-1、细胞凋亡、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。本发明还涉及使用本发明的化合物和组合物抑制ICE活性、治疗白细胞介素-1β、细胞凋亡、IGIF和IFN-γ介导的疾病以及减少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&bgr; converting enzyme
  申请人：Vertex Pharmaceuticals, Incorporated

  公开号：US06258948B1

  公开（公告）日：2001-07-10

  The present invention relates to novel classes of compounds which are inhibitors of interleukin-IB 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-&ggr;-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-&ggr;-mediated diseases and decreasing IGIF and IFN-&ggr; 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，它们是白细胞介素-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、骨质破坏性疾病、增生性疾病、传染性疾病、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的化合物和组合物抑制ICE活性、治疗白细胞介素-1β、凋亡、IGIF和IFN-γ介导的疾病、以及减少IGIF和IFN-γ的产生的方法。本发明还涉及制备N-酰胺化合物的方法。