diphenyl 1-acetamido-2-(4-(N,N'-bis(tert-butyloxycarbonyl)guanidino)phenyl)-ethylphosphonate

• 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: diphenyl 1-acetamido-2-(4-(N,N'-bis(tert-butyloxycarbonyl)guanidino)phenyl)-ethylphosphonate
• 英文别名: tert-butyl N-[N'-[4-(2-acetamido-2-diphenoxyphosphorylethyl)phenyl]-N-[(2-methylpropan-2-yl)oxycarbonyl]carbamimidoyl]carbamate
• 化学式: C₃₃H₄₁N₄O₈P
• 分子量: 652.684
• InChiKey: BKSLWSLYJOSHFB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.3
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  154
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 diphenyl 1-acetamido-2-(4-(N,N'-bis(tert-butyloxycarbonyl)guanidino)phenyl)-ethylphosphonate 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 diphenyl 1-acetamido-2-(4-guanidinophenyl)ethylphosphonate trifluoroacetate
  参考文献：
  名称：

  Small, Potent, and Selective Diaryl Phosphonate Inhibitors for Urokinase-Type Plasminogen Activator with In Vivo Antimetastatic Properties

  摘要：

  A set of small nonpeptidic diaryl phosphonate inhibitors was prepared. Some of these inhibitors show potent and highly selective irreversible uPA inhibition. The biochemical and modeling data prove that the combination of a benzylguanidine moiety with a diaryl phosphonate ester results in optimized molecules for derivatizing the serine alcohol in the uPA active site. Selected compounds show significant antimetastatic effects in the BN-472 rat mammary carcinoma model. We report in this paper a preclinical proof of concept that selective, irreversible uPA inhibitors could be valuable in antimetastatic therapy.

  DOI：

  10.1021/jm700962j
• 作为产物：
  描述：

  乙酰氯 、 diphenyl 1-amino-2-(4-(N,N'-bis(tert-butyloxycarbonyl)guanidino)phenyl)ethyl-phosphonate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.17h， 生成 diphenyl 1-acetamido-2-(4-(N,N'-bis(tert-butyloxycarbonyl)guanidino)phenyl)-ethylphosphonate
  参考文献：
  名称：

  WO2007/45496

  摘要：

  公开号：

文献信息

• Novel Urokinase Inhibitors
  申请人：Augustyns Koen

  公开号：US20080312191A1

  公开（公告）日：2008-12-18

  The present invention relates to novel compounds with inhibitory activity towards urokinase plasminogen activator (uPA); to methods for preparation of said uPA inhibitor compounds; to pharmaceutical compositions comprising said uPA inhibitor compounds; to the use of said uPA inhibitor compounds as a medicament and the use of said uPA inhibitor compounds for the preparation of a medicament for the treatment of conditions chosen from the group comprising cancer, tumour growth, tumour invasion, tumour metastasis, diabetic retinopathy, hemorrhagic atherosclerosis and inflammatory conditions, such as rheumatoid arthritis and psoriasis.

  本发明涉及具有抑制尿激酶纤溶酶原活化物（uPA）活性的新化合物；制备所述uPA抑制剂化合物的方法；包括所述uPA抑制剂化合物的药物组合物；将所述uPA抑制剂化合物用作药物的用途以及将所述uPA抑制剂化合物用于制备用于治疗癌症、肿瘤生长、肿瘤侵袭、肿瘤转移、糖尿病视网膜病变、出血性动脉粥样硬化和类风湿性关节炎和银屑病等条件的药物的用途。
• Small, Potent, and Selective Diaryl Phosphonate Inhibitors for Urokinase-Type Plasminogen Activator with In Vivo Antimetastatic Properties
  作者：Jurgen Joossens、Omar M. Ali、Ibrahim El-Sayed、Georgiana Surpateanu、Pieter Van der Veken、Anne-Marie Lambeir、Buddy Setyono-Han、John A. Foekens、Anneliese Schneider、Wolfgang Schmalix、Achiel Haemers、Koen Augustyns

  DOI：10.1021/jm700962j

  日期：2007.12.27

  A set of small nonpeptidic diaryl phosphonate inhibitors was prepared. Some of these inhibitors show potent and highly selective irreversible uPA inhibition. The biochemical and modeling data prove that the combination of a benzylguanidine moiety with a diaryl phosphonate ester results in optimized molecules for derivatizing the serine alcohol in the uPA active site. Selected compounds show significant antimetastatic effects in the BN-472 rat mammary carcinoma model. We report in this paper a preclinical proof of concept that selective, irreversible uPA inhibitors could be valuable in antimetastatic therapy.
• WO2007/45496
  申请人：——

  公开号：——

  公开（公告）日：——