(S)-四氢-1,3(2H)-哒嗪二羧酸 3-叔丁酯 1-(苯甲基)酯 | 72064-51-8

• 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
• 中文名称: (S)-四氢-1,3(2H)-哒嗪二羧酸 3-叔丁酯 1-(苯甲基)酯
• 中文别名: (S)-1-苄氧羰基-3-叔丁基六氢哒嗪-1,3-二羧酸酯；(S)-四氢-1,3(2H)-哒嗪二羧酸3-叔丁酯1-(苯甲基)酯
• 英文名称: (3S)-N¹-benzyloxycarbonyl-piperazic acid tert-butyl ester
• 英文别名: tert-butyl (3S)-1-benzyloxycarbonylhexahydropyridazine-3-carboxylate；(3S)-1-benzyl 3-t-butyl hexahydropyridazine-1,3-dicarboxylate；(S)-1-Benzyl 3-tert-butyl tetrahydropyridazine-1,3(2H)-dicarboxylate；1-O-benzyl 3-O-tert-butyl (3S)-diazinane-1,3-dicarboxylate
• CAS: 72064-51-8
• 化学式: C₁₇H₂₄N₂O₄
• 分子量: 320.389
• InChiKey: DOUUPKDLDFXKDX-AWEZNQCLSA-N

物化性质

• 沸点：
  415.3±55.0 °C(Predicted)
• 密度：
  1.148

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  (S)-四氢-1,3(2H)-哒嗪二羧酸 3-叔丁酯 1-(苯甲基)酯 在 palladium on activated charcoal 盐酸 、 氯化亚砜 、 硼烷四氢呋喃络合物 、 氢气 、 碳酸氢钠 、 sodium carbonate 、 一水合肼 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 64.0h， 生成 西拉普利
  参考文献：
  名称：

  Attwood, Michael R.; Hassall, Cedric H.; Kroehn, Antonin, Journal of the Chemical Society. Perkin transactions I, 1986, p. 1011 - 1020

  摘要：

  DOI：
• 作为产物：
  描述：

  5-溴戊酰氯 在 N,N-二甲基丙烯基脲 、 lithium hydroxide 、 sodium hydroxide 、 正丁基锂 、 硫酸 、 四丁基碘化铵 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 (S)-四氢-1,3(2H)-哒嗪二羧酸 3-叔丁酯 1-(苯甲基)酯
  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。
• Synthesis and Structure-Activity Relationships of Gelatinase Inhibitors Derived from Matlystatins.
  作者：Kazuhiko TAMAKI、Kazuhiko TANZAWA、Shinwa KURIHARA、Tetsuo OIKAWA、Sayako MONMA、Kohei SHIMADA、Yukio SUGIMURA

  DOI：10.1248/cpb.43.1883

  日期：——

  To investigate a series of new inhibitors of gelatinases based on matlystatin B (1b), extensive structure-activity relationship studies were performed. The new derivatives were evaluated in vitro for the ability to inhibit gelatinases. The inhibitory activities against thermolysin were also assayed to test the compounds' selectivity. Among the compounds modified at the P'3 moiety, the N-methylamide

  为了研究一系列基于matlystatin B（1b）的明胶酶抑制剂，进行了广泛的构效关系研究。在体外评估了新衍生物抑制明胶酶的能力。还测定了对嗜热菌素的抑制活性以测试化合物的选择性。在P'3部分修饰的化合物中，N-甲基酰胺衍生物5 g对明胶酶B的作用实际上是母体化合物1b的两倍（5g，IC50 = 0.27 microM与1b，IC50 = 0.57 microM）。其他衍生物，包括1）具有酯部分P'2和P'3的酯7a和7b，2）环状氨基酸，带有P'2的L-脯氨酸或L-哌啉酸（13a和13b），和3）化合物29a和29b代表戊基侧链在C3'（P' 1个侧链）代替C2'，均显示效力降低。关键发现是观察到在P'1位置引入壬基会产生一种化合物（31f，IC50 = 0.0012 microM），具有对明胶酶的高抑制活性和相对于嗜热菌蛋白酶的高选择性。该结果表明明胶酶的S'1亚位点具有局部深的疏水
• Matlystatins, new inhibitors of type IV collagenases from Actinomadura atramentaria. IV. Synthesis and structure-activity relationships of matlystatin b and its stereoisomers.
  作者：KAZUHIKO TAMAKI、SHINWA KURIHARA、TETSUO OIKAWA、KAZUHIKO TANZAWA、YUKIO SUGIMURA

  DOI：10.7164/antibiotics.47.1481

  日期：——

  The first total synthesis of matlystatin B (1a), a low molecular weight inhibitor of type IV collagenases, was accomplished, and its absolute configuration was unambiguously determined. Furthermore, ten stereoisomers of 1a were synthesized, and the inhibition of the 92 kDa type IV collagenase and of other metalloproteinases by each stereoisomer was investigated.

  首次全合成了 IV 型胶原酶的低分子量抑制剂 matlystatin B (1a)，并明确确定了其绝对构型。此外，合成了1a的十种立体异构体，并研究了每种立体异构体对92 kDa IV型胶原酶和其他金属蛋白酶的抑制作用。
• 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。