1-((1-formyl-3-phenylpropylcarbamoyl)-3-methylbutyl)morpholine-4-carboxamide | 438044-70-3

• 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: 1-((1-formyl-3-phenylpropylcarbamoyl)-3-methylbutyl)morpholine-4-carboxamide
• 英文别名: (S)-2-(N-(Morpholinocarbonyl)leucyl)amino-4-phenylbutanal；N-[(2S)-4-methyl-1-oxo-1-[[(2S)-1-oxo-4-phenylbutan-2-yl]amino]pentan-2-yl]morpholine-4-carboxamide
• CAS: 438044-70-3
• 化学式: C₂₁H₃₁N₃O₄
• 分子量: 389.495
• InChiKey: XNRCJIGMJOWOAZ-OALUTQOASA-N

物化性质

• 熔点：
  58-60 °C
• 沸点：
  660.0±55.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-((1-formyl-3-phenylpropylcarbamoyl)-3-methylbutyl)morpholine-4-carboxamide 在 sodium cyanoborohydride 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成
  参考文献：
  名称：

  有效的和二硫化物作为组织蛋白酶S抑制剂的设计。

  摘要：

  描述和设计和合成作为半胱氨酸蛋白酶组织蛋白酶S的选择性抑制剂的二肽基二硫化物和二肽基苯甲酰基hydr。预期这些抑制剂会形成组织蛋白酶S活性位点半胱氨酸的缓慢可逆的共价加合物。通过质谱分析证实了初始加合物的形成。探索了这些加合物的性质和机理。苯甲酰的动力学分析表明，这些抑制剂可作为组织蛋白酶S的不可逆抑制剂。此外，已证明苯甲酰shown在体外和体内均是组织蛋白酶S处理II类相关不变肽的有效抑制剂。

  DOI：

  10.1016/s0968-0896(02)00468-6
• 作为产物：
  描述：

  N-(morpholinocarbonyl)-Leu 在 N-甲基吗啉 、 lithium aluminium tetrahydride 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 1.25h， 生成 1-((1-formyl-3-phenylpropylcarbamoyl)-3-methylbutyl)morpholine-4-carboxamide
  参考文献：
  名称：

  有效的和二硫化物作为组织蛋白酶S抑制剂的设计。

  摘要：

  描述和设计和合成作为半胱氨酸蛋白酶组织蛋白酶S的选择性抑制剂的二肽基二硫化物和二肽基苯甲酰基hydr。预期这些抑制剂会形成组织蛋白酶S活性位点半胱氨酸的缓慢可逆的共价加合物。通过质谱分析证实了初始加合物的形成。探索了这些加合物的性质和机理。苯甲酰的动力学分析表明，这些抑制剂可作为组织蛋白酶S的不可逆抑制剂。此外，已证明苯甲酰shown在体外和体内均是组织蛋白酶S处理II类相关不变肽的有效抑制剂。

  DOI：

  10.1016/s0968-0896(02)00468-6

文献信息

• Compounds, compositions and methods for treatment of parasitic infections
  申请人：——

  公开号：US20020107266A1

  公开（公告）日：2002-08-08

  Compounds and pharmaceutical compositions useful as anti-parasitic agents agents, particularly in the treatment, prevention or amelioration of one or more symptoms of malaria or Chagas' disease, are provided. In particular, methods of modulating the activity of falcipain or cruzain, preferably inhibiting falcipain or cruzain, with the compounds and compositions are provided.

  提供了作为抗寄生虫药剂的化合物和药物组合物，特别是用于治疗、预防或缓解疟疾或充满病症状之一的药剂。具体而言，提供了利用这些化合物和组合物调节falcipain或cruzain活性的方法，优选抑制falcipain或cruzain的方法。
• [EN] PROTEASE TRANSITION STATE INHIBITOR PRODRUGS<br/>[FR] PROMÉDICAMENTS D'INHIBITEURS D'ÉTATS DE TRANSITION PROTÉASIQUES
  申请人：UNIV KANSAS STATE

  公开号：WO2018023054A1

  公开（公告）日：2018-02-01

  Disclosed herein are protease transition state inhibitor/analogue prodrug compounds selected from the group consisting of esters, carbamates, ester phosphates, and pharmaceutically acceptable salts thereof. Compositions containing such prodrugs are also disclosed, along with methods of using such compounds therapeutically or prophylactically against calicivirus, picornavirus, and/or coronavirus infection, as well as other conditions, such as malaria, cancer, stroke, heart attack, neural degeneration, cataracts, and glaucoma through inhibition of the variety of proteases associated with progression of such conditions.

  本文披露了一组蛋白酶过渡态抑制剂/类似物前药化合物，所述化合物选自酯、氨基甲酸酯、酯磷酸酯和其药学上可接受的盐。还披露了含有这些前药的组合物，以及使用这些化合物的方法，用于治疗或预防钙病毒、小肠病毒和/或冠状病毒感染，以及其他疾病，如疟疾、癌症、中风、心脏病发作、神经退行性疾病、白内障和青光眼，通过抑制与这些疾病进展相关的多种蛋白酶。
• Protease transition state inhibitor prodrugs
  申请人：Kansas State University Research Foundation

  公开号：US11033600B2

  公开（公告）日：2021-06-15

  Disclosed herein are protease transition state inhibitor/analogue prodrug compounds selected from the group consisting of esters, carbamates, ester phosphates, and pharmaceutically acceptable salts thereof. Compositions containing such prodrugs are also disclosed, along with methods of using such compounds therapeutically or prophylactically against calicivirus, picornavirus, and/or coronavirus infection, as well as other conditions, such as malaria, cancer, stroke, heart attack, neural degeneration, cataracts, and glaucoma through inhibition of the variety of proteases associated with progression of such conditions.

  本文公开了选自酯、氨基甲酸酯、酯磷酸盐及其药学上可接受的盐组成的组的蛋白酶过渡态抑制剂/类似物原药化合物。此外，还公开了含有此类原药的组合物，以及使用此类化合物通过抑制与此类病症进展相关的各种蛋白酶，治疗或预防钙病毒、皮卡病毒和/或冠状病毒感染以及其他病症（如疟疾、癌症、中风、心脏病、神经变性、白内障和青光眼）的方法。
• Endoperoxide Carbonyl Falcipain 2/3 Inhibitor Hybrids: Toward Combination Chemotherapy of Malaria through a Single Chemical Entity
  作者：Peter Gibbons、Edite Verissimo、Nuna C. Araujo、Victoria Barton、Gemma L. Nixon、Richard K. Amewu、James Chadwick、Paul A. Stocks、Giancarlo A. Biagini、Abhishek Srivastava、Philip J. Rosenthal、Jiri Gut、Rita C. Guedes、Rui Moreira、Raman Sharma、Neil Berry、M. Lurdes S. Cristiano、Alison E. Shone、Stephen A. Ward、Paul M. O’Neill

  DOI：10.1021/jm1009567

  日期：2010.11.25

  We extend our approach of combination chemotherapy through a single prodrug entity (O'Neill et al. Angew. Chem., Int. Ed. 2004, 43, 4193) by using a 1,2,4-trioxolane as a protease inhibitor carbonyl-masking group. These molecules are designed to target the malaria parasite through two independent mechanisms of action: iron(II) decomposition releases the carbonyl protease inhibitor and potentially eytotoxic C-radical species in tandem. Using a proposed target "heme", we also demonstrate heme alkylation/carbonyl inhibitor release and quantitatively measure endoperoxide turnover in parasitized red blood cells.
• PROTEASE TRANSITION STATE INHIBITOR PRODRUGS
  申请人：Kansas State University Research Foundation

  公开号：US20190151400A1

  公开（公告）日：2019-05-23

  Disclosed herein are protease transition state inhibitor/analogue prodrug compounds selected from the group consisting of esters, carbamates, ester phosphates, and pharmaceutically acceptable salts thereof. Compositions containing such prodrugs are also disclosed, along with methods of using such compounds therapeutically or prophylactically against calicivirus, picornavirus, and/or coronavirus infection, as well as other conditions, such as malaria, cancer, stroke, heart attack, neural degeneration, cataracts, and glaucoma through inhibition of the variety of proteases associated with progression of such conditions.