[(S)-3-Cyano-1-isopropyl-2-oxo-3-(triphenyl-λ5-phosphanylidene)-propyl]-carbamic acid benzyl ester | 214122-02-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(S)-3-Cyano-1-isopropyl-2-oxo-3-(triphenyl-λ5-phosphanylidene)-propyl]-carbamic acid benzyl ester
• CAS: 214122-02-8
• 化学式: C₃₃H₃₁N₂O₃P
• 分子量: 534.595
• InChiKey: KAZHKDREGMSSOD-HKBQPEDESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  39.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  79.19
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  [(S)-3-Cyano-1-isopropyl-2-oxo-3-(triphenyl-λ5-phosphanylidene)-propyl]-carbamic acid benzyl ester 在 三氯化硼 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 臭氧 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 benzyl N-[(2S)-1-[[(3S)-1-(benzylamino)-4-methyl-1,2-dioxopentan-3-yl]amino]-1-oxopentan-2-yl]carbamate
  参考文献：
  名称：

  Development of α-keto-based inhibitors of cruzain, a cysteine protease implicated in Chagas disease

  摘要：

  Trypanosoma cruzi, a protozoan parasite, is the causative agent of Chagas disease, a major cause of cardiovascular disease in many Latin American countries. There is an urgent need to develop an improved therapy due to the toxicity of existing drugs and emerging drug resistance. Cruzain, the primary cysteine protease of T cruzi, is essential for the survival of the parasite in host cells and therefore is an important target for the development of inhibitors as potential therapeutics. A novel series of alpha-ketoamide-, alpha-ketoacid-, alpha-ketoester-, and aldehyde-based inhibitors of cruzain has been developed. The inhibitors were identified by screening protease targeted small molecule libraries and systematically optimizing the P1, P2, P3, and P1 ' residues using specific structure-guided methods. A total of 20 compounds displayed picomolar potency in in vitro assays and three inhibitors representing different alpha-keto-based inhibitor scaffolds demonstrated anti-trypanosomal activity in cell culture. A 2.3 angstrom crystallographic structure of cruzain bound with one of the alpha-ketoester analogs is also reported. The structure and kinetic assay data illustrate the covalent binding, reversible inhibition mechanism of the inhibitor. Information on the compounds reported here will be useful in the development of new lead compounds as potential therapeutic agents for the treatment of Chagas disease and as biological probes to study the role that cruzain plays in the pathology. This study also demonstrates the validity of structure-guided approaches to focused library design and lead compound optimization. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.12.053
• 作为产物：
  描述：

  氰甲基三苯基氯化磷 、 (S)-3-苄氧羰基-4-异丙基-2,5-恶唑烷二酮 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.75h， 以71%的产率得到[(S)-3-Cyano-1-isopropyl-2-oxo-3-(triphenyl-λ5-phosphanylidene)-propyl]-carbamic acid benzyl ester
  参考文献：
  名称：

  由UNCA合成氰基酮基膦酸酯，β-氨基-α-酮基酯的前体

  摘要：

  由N-氨基甲酸酯保护的α-氨基酸N-羧基酸酐（UNCA）通过与氰基甲基三苯基chloride氯化物反应，以高收率合成了N-保护氨基酸的氰基亚甲基三苯基膦。这些化合物是α-酮酯的前体，它们是模拟酶抑制剂中四面体过渡态的候选物。

  DOI：

  10.1016/s0040-4039(98)01504-4