(2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester | 160806-33-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: (2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester
• 英文别名: N-allyloxycarbonyl-4-amino-5-benzyloxy-2-oxotetrahydrofuran；3-allyloxycarbonylamino-2-(benzyl)oxy-5-oxotetrahydrofuran；(3S,2RS)3-allyloxycarbonylamino-2-benzyloxy-5-oxotetrahydrofuran；prop-2-enyl N-(5-oxo-2-phenylmethoxyoxolan-3-yl)carbamate
• CAS: 160806-33-7
• 化学式: C₁₅H₁₇NO₅
• mdl: MFCD26393307
• 分子量: 291.304
• InChiKey: ZEZKRQQOECKKCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  484.7±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  73.9
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester 以54%的产率得到1-[2-(4-Amino-3-chloro-benzoylamino)-propionyl]-4-fluoro-pyrrolidine-2-carboxylic Acid (2-Benzyloxy-5-oxo-tetrahydro-furan-3-yl)-amide
  参考文献：
  名称：

  Inhibitors of caspases

  摘要：

  本发明涉及一类新型化合物，这些化合物是半胱氨酸蛋白酶抑制剂，特别是白细胞介素-1β转化酶（“ICE”）抑制剂。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半胱氨酸蛋白酶活性，因此，可以有利地用作对抗白细胞介素-1（“IL-1”）、凋亡、干扰素-γ诱导因子（IGIF）或干扰素-γ（“IFN-γ”）介导疾病的药剂，包括炎症性疾病、自身免疫疾病、破坏性骨疾病、增生性疾病、传染性疾病和退行性疾病。本发明还涉及通过使用本发明的化合物和组合物来抑制半胱氨酸蛋白酶活性、降低IGIF产生和IFN-γ产生以及治疗白细胞介素-1、凋亡和干扰素-γ介导疾病的方法。本发明还涉及制备本发明化合物的方法。

  公开号：

  US06531474B1

文献信息

• Inhibitors of interleukin-1.beta. converting enzyme
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US05874424A1

  公开（公告）日：1999-02-23

  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介导疾病、凋亡介导疾病、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剂。本发明还涉及抑制ICE活性的方法以及使用本发明的化合物和组合物治疗白细胞介素-1介导疾病的方法。
• Inhibitors of interleukin-1&bgr; Converting enzyme inhibitors
  申请人：Vertex Pharmaceuticals Incorporated

  公开号：US06204261B1

  公开（公告）日：2001-03-20

  The present invention relates to pyradazino[1,2-a][1,2]diazepine-1-carboxamide compounds of formula: which compounds are inhibitors of interleukin-1beta converting enzyme.

  这项发明涉及公式如下的吡啶并[1,2-a][1,2]二氮杂环庚烷-1-羧酰胺化合物，这些化合物是白细胞介素-1β转化酶的抑制剂。
• 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。
• Asymmetric synthesis of piperazic acid and derivatives thereof
  申请人：——

  公开号：US20030176691A1

  公开（公告）日：2003-09-18

  This invention provides a concise, asymmetric synthesis of piperazic acid and derivatives thereof, whereby either the (3S)- or (3R)-enantiomeric form may be obtained with high optical purity. (3S)-piperazic acid is derived from D-glutamic acid through an (R)-2,5-dihydroxyvalerate ester intermediate. After the hydroxy groups are converted to suitable leaving groups, such as mesylates, the ester is treated with a bis-protected hydrazine to provide the desired (3S)-piperazic acid derivative. The (3R) enantiomer of piperazic acid may be similarly obtained starting with L-glutamic acid. The method may also be used to obtain piperazic acid derivatives that have moderate optical purity or are racemic. By this method, piperazic acid derivatives may be obtained that are useful as intermediates for pharmacologically active compounds. For example, certain intermediates of this invention are useful for preparing caspase inhibitors, particularly inhibitors of ICE, through additional steps known in the art.

  这个发明提供了一种简洁的、不对称的对哌嗪酸及其衍生物的合成方法，可以高度纯化得到(3S)-或(3R)-对映体。(3S)-对哌嗪酸是从D-谷氨酸通过(R)-2,5-二羟基戊酸酯中间体得到的。在羟基被转化为适当的离去基，如甲磺酸酯之后，酯被处理成双保护肼，以提供所需的(3S)-对哌嗪酸衍生物。(3R)对映体的对哌嗪酸也可以通过类似的方法从L-谷氨酸开始获得。该方法也可用于获得具有中等光学纯度或是外消旋的对哌嗪酸衍生物。通过这种方法，可以获得作为药理活性化合物中间体有用的对哌嗪酸衍生物。例如，本发明的某些中间体可用于制备半胱氨酸蛋白酶抑制剂，特别是ICE的抑制剂，通过已知的其他步骤。
• Peptidyl derivatives as inhibitors of interleukin-1.beta. converting
  申请人：Merck & Co., Inc.

  公开号：US05434248A1

  公开（公告）日：1995-07-18

  Novel peptidyl derivatives of formula I are found to be potent inhibitors of interleukin-1.beta. converting enzyme (ICE). Compounds of formula I may be useful in the treatment of inflammatory or immune-based diseases of the lung and airways; central nervous system and surrounding membranes; the eyes and ears; joints, bones, and connective tissues; cardiovascular system including the pericardium; the gastrointestinal and urogenital systems; the skin and mucosal membranes. Compounds of formula I are also useful in treating the complications of infection (e.g., gram negative shock) and tumors in which IL 1 functions as an autocrine growth factor or as a mediator of cachexia. ##STR1##

  公式I的新型肽衍生物被发现是强效的白细胞介素-1β转化酶（ICE）抑制剂。公式I的化合物可能在治疗肺和气道的炎症或免疫性疾病；中枢神经系统和周围膜；眼睛和耳朵；关节、骨骼和结缔组织；包括心包在内的心血管系统；消化和泌尿系统；皮肤和黏膜膜方面有用。公式I的化合物还可用于治疗感染的并发症（如革兰氏阴性休克）和肿瘤，其中白细胞介素1作为自分泌生长因子或消耗症的介质。 ##STR1##