3-({1-[2-(4-Amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carbonyl}-amino)-4-oxo-butyric Acid | 853017-38-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 3-({1-[2-(4-Amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carbonyl}-amino)-4-oxo-butyric Acid
• 英文别名: 3-[[1-[2-[(4-Amino-3-chlorobenzoyl)amino]-3,3-dimethylbutanoyl]pyrrolidine-2-carbonyl]amino]-4-oxobutanoic acid
• CAS: 853017-38-6
• 化学式: C₂₂H₂₉ClN₄O₆
• 分子量: 480.948
• InChiKey: SOZONDBMOYWSRW-UHFFFAOYSA-N

物化性质

• 沸点：
  761.6±60.0 °C(Predicted)
• 密度：
  1.342±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  159
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-[2-(4-Amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carboxylic Acid (2-Benzyloxy-5-oxo-tetrahydro-furan-3-yl)-amide 以74%的产率得到3-({1-[2-(4-Amino-3-chloro-benzoylamino)-3,3-dimethyl-butyryl]-pyrrolidine-2-carbonyl}-amino)-4-oxo-butyric Acid
  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

• PRODRUG OF AN ICE INHIBITOR
  申请人：Wannamaker Marion W.

  公开号：US20090012149A1

  公开（公告）日：2009-01-08

  This invention describes an ICE inhibitor prodrug (I) having good bioavailability. Compound I is useful for treating IL-1 mediated diseases such as rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, inflammatory peritonitis, septic shock, pancreatitis, traumatic brain injury, organ transplant rejection, osteoarthritis, asthma, psoriasis, Alzheimer's disease, myocardial infarction, congestive heart failure, Huntington's disease, atherosclerosis, atopic dermatitis, leukemias and related disorders, myelodysplastic syndrome, uveitis or multiple myeloma.

  该发明描述了一种具有良好生物利用度的ICE抑制剂前药(I)。化合物I可用于治疗IL-1介导的疾病，如类风湿性关节炎、炎症性肠病、克罗恩病、溃疡性结肠炎、炎性腹膜炎、感染性休克、胰腺炎、创伤性脑损伤、器官移植排斥、骨关节炎、哮喘、银屑病、阿尔茨海默病、心肌梗死、充血性心力衰竭、亨廷顿病、动脉硬化、特应性皮炎、白血病及相关疾病、骨髓增生异常综合症、葡萄膜炎或多发性骨髓瘤。
• Inhibitors of caspase
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2011800A2

  公开（公告）日：2009-01-07

  The present invention relates to novel classes of compounds which are caspase inhibitors, in particular interleukin-1β converting enzyme ("ICE") inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting caspase activity and consequently, may be advantageously used as agents against interleukin-1- ("IL-1"), apoptosis-, interferon-γ inducing factor-(IGIF), or interferon-γ-("IFN-γ") mediated diseases, including inflammatory diseases, autoimmune diseases, destructive bone disorders, proliferative disorders, infectious diseases, and degenerative diseases. This invention also relates to methods for inhibiting caspase activity and decreasing IGIF production and IFN-γ production and methods for treating interleukin-1, apoptosis-, and interferon-γ mediated diseases using the compounds and compositions of this invention. This invention also relates to methods of preparing the compounds of this invention.

  本发明涉及一类新型化合物，它们是 Caspase 抑制剂，特别是白细胞介素-1β 转换酶（"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 caspase 活性，因此可作为抗白细胞介素-1-（"IL-1"）、细胞凋亡、干扰素-γ 诱导因子（IGIF）或干扰素-γ-（"IFN-γ"）介导的疾病的药物，包括炎症性疾病、自身免疫性疾病、破坏性骨疾病、增殖性疾病、传染性疾病和退行性疾病。本发明还涉及抑制 Caspase 活性、减少 IGIF 生成和 IFN-γ 生成的方法，以及使用本发明化合物和组合物治疗白细胞介素-1、细胞凋亡和干扰素-γ 介导的疾病的方法。本发明还涉及制备本发明化合物的方法。
• Methods for overcoming glucocorticoid resistance and for determining glucocorticoid resistance potential in cancer
  申请人：St. Jude Children's Research Hospital, Inc.

  公开号：US10457946B2

  公开（公告）日：2019-10-29

  The invention provides methods for overcoming glucocorticoid resistance of cancers by inhibition of CASP1. Also disclosed are diagnostic methods for determining glucocorticoid resistance potential by measuring expression level or promoter methylation status of CASP1 gene and/or NLRP3 gene.

  本发明提供了通过抑制 CASP1 来克服癌症的糖皮质激素抗性的方法。本发明还公开了通过测量 CASP1 基因和/或 NLRP3 基因的表达水平或启动子甲基化状态来确定糖皮质激素耐药性潜力的诊断方法。
• Caspase-1 inhibition and uses thereof for prevention and treatment of neurological conditions
  申请人：Leblanc Andrea

  公开号：US11160788B2

  公开（公告）日：2021-11-02

  Described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating a neurological condition (e.g., a neurodegenerative disease (e.g., Alzheimer's disease)) in a subject, based on caspase-1 inhibition. Also described herein are methods for preventing, delaying the onset or reducing the severity of, preventing or reversing the progression of, or treating cognitive impairment in a subject, based on caspase-1 inhibition. Corresponding uses and kits are also described. In an embodiment, the caspase-1 inhibitor is VX-765 or a pharmaceutically acceptable salt thereof.

  本文描述了基于caspase-1抑制的预防、延迟发病或降低严重程度、预防或逆转进展或治疗受试者神经系统疾病（如神经退行性疾病（如阿尔茨海默病））的方法。本文还描述了基于caspase-1抑制的预防、延缓发病或减轻严重程度、预防或逆转进展或治疗受试者认知障碍的方法。还描述了相应的用途和试剂盒。在一个实施方案中，caspase-1抑制剂是VX-765或其药学上可接受的盐。
• INHIBITORS OF CASPASES
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1064298A2

  公开（公告）日：2001-01-03