3-[[(2R,3S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]sulfamoylmethyl]benzoic acid | 446846-63-5

• 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: 3-[[(2R,3S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]sulfamoylmethyl]benzoic acid
• CAS: 446846-63-5
• 化学式: C₂₅H₃₃N₅O₇S₂
• 分子量: 579.698
• InChiKey: AXPWDMKWJUPXPM-ONGXBYRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  39
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  245
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 3-[[(2R,3S)-1-[[(2S)-1-[(4-carbamimidoylphenyl)methylamino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]sulfamoylmethyl]benzoic acid
  参考文献：
  名称：

  Factor VIIa inhibitors: Target hopping in the serine protease family using X-ray structure determination

  摘要：

  Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. Compound 1 was discovered from focused screening of serine protease-directed compounds from our internal collection. Using parallel synthesis supported by structure-based drug design, we identified peptidemimetic FVIIa/TF inhibitors (compounds 4-11) containing L-Gln or L-Met as the P2 moiety. However, these compounds lacked the selectivity of other serine proteases in the coagulation cascade, especially thrombin. Further optimization of these compounds was carried out with a focus on the P4 moiety. Among the optimized compounds, 12b-f showed improved selectivity. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.07.044

文献信息

• Factor VIIa inhibitors: Target hopping in the serine protease family using X-ray structure determination
  作者：Takuya Shiraishi、Shojiro Kadono、Masayuki Haramura、Hirofumi Kodama、Yoshiyuki Ono、Hitoshi Iikura、Tohru Esaki、Takaki Koga、Kunihiro Hattori、Yoshiaki Watanabe、Akihisa Sakamoto、Kazutaka Yoshihashi、Takehisa Kitazawa、Keiko Esaki、Masateru Ohta、Haruhiko Sato、Toshiro Kozono

  DOI：10.1016/j.bmcl.2008.07.044

  日期：2008.8

  Selective factor VIIa-tissue factor complex (FVIIa/TF) inhibition is regarded as a promising target for developing new anticoagulant drugs. Compound 1 was discovered from focused screening of serine protease-directed compounds from our internal collection. Using parallel synthesis supported by structure-based drug design, we identified peptidemimetic FVIIa/TF inhibitors (compounds 4-11) containing L-Gln or L-Met as the P2 moiety. However, these compounds lacked the selectivity of other serine proteases in the coagulation cascade, especially thrombin. Further optimization of these compounds was carried out with a focus on the P4 moiety. Among the optimized compounds, 12b-f showed improved selectivity. (c) 2008 Elsevier Ltd. All rights reserved.