N-[2-({[amino(azanylidene)methyl]amino}oxy)ethyl]-2-{6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl}ethanamide | 409081-52-3

• 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: N-[2-({[amino(azanylidene)methyl]amino}oxy)ethyl]-2-{6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl}ethanamide
• 英文别名: N-[2-({[amino(imino)methyl]amino}oxy)ethyl]-2-{6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl}acetamide；N-[2-(amidinoaminooxy)ethyl]-2-{3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}ethanamide；N-[2-(Amidinoaminooxy)ethyl]-2-{3-[(2,2-difluoro-2-phenylethyl)amino]-6-chloro-2-fluorophenyl}acetamide；2-[6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl]-N-[2-(diaminomethylideneamino)oxyethyl]acetamide
• CAS: 409081-52-3
• 化学式: C₁₉H₂₁ClF₃N₅O₂
• 分子量: 443.856
• InChiKey: DZEJHPMTDNDECN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  115
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  tert-butyl N-[N'-[2-[[2-[6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl]acetyl]amino]ethoxy]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 N-[2-({[amino(azanylidene)methyl]amino}oxy)ethyl]-2-{6-chloro-3-[(2,2-difluoro-2-phenylethyl)amino]-2-fluorophenyl}ethanamide
  参考文献：
  名称：

  2-(2-Chloro-6-fluorophenyl)acetamides as potent thrombin inhibitors

  摘要：

  2-(2-Chloro-6-fluorophenyl)acetamides having 2,2-difluoro-2-aryl/heteroaryl-ethylamine P3 and oxyguanidine P1 substituents are potent thrombin inhibitors (K(i)=0.9-33.9 nM). 2-(5-Chloro-pyridin-2-yl)-2,2-difluoroethylamine was the best P3 substituent, yielding the most potent inhibitor (K(i)=0.7 nM). Replacing the P3 heteroaryl group with a phenyl ring or replacing the difluoro substitution with dimethyl or cyclopropyl groups in the linker reduced the affinity for thrombin significantly. The aminopyridine P1s also provided an increase in potency.

  DOI：

  10.1016/j.bmcl.2007.09.013

文献信息

• AMINOPYRIDINYL-, AMINOGUANIDINYL- AND ALKOXYGUANIDINYL- SUBSTITUTED PHENYL ACETAMIDES AS PROTEASE INHIBITORS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1324981B1

  公开（公告）日：2006-08-23
• IDENTIFICATION AND TARGETED MODULATION OF GENE SIGNALING NETWORKS
  申请人：CAMP4 THERAPEUTICS CORPORATION

  公开号：US20210254056A1

  公开（公告）日：2021-08-19

  The present invention provides methods and compositions for the evaluation, alteration and/or optimization of gene signaling. Methods and systems are also provided which exploit the information generated in the identification of new targets and non-canonical signaling pathways.
• 2-(2-Chloro-6-fluorophenyl)acetamides as potent thrombin inhibitors
  作者：Lily Lee、Kevin D. Kreutter、Wenxi Pan、Carl Crysler、John Spurlino、Mark R. Player、Bruce Tomczuk、Tianbao Lu

  DOI：10.1016/j.bmcl.2007.09.013

  日期：2007.11

  2-(2-Chloro-6-fluorophenyl)acetamides having 2,2-difluoro-2-aryl/heteroaryl-ethylamine P3 and oxyguanidine P1 substituents are potent thrombin inhibitors (K(i)=0.9-33.9 nM). 2-(5-Chloro-pyridin-2-yl)-2,2-difluoroethylamine was the best P3 substituent, yielding the most potent inhibitor (K(i)=0.7 nM). Replacing the P3 heteroaryl group with a phenyl ring or replacing the difluoro substitution with dimethyl or cyclopropyl groups in the linker reduced the affinity for thrombin significantly. The aminopyridine P1s also provided an increase in potency.