methyl 1-(bis-(4-acetamidophenoxy)phosphoryl)-2-(4-(tert-butyloxycarbonylamino)phenyl)ethylcarbamate

• 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: methyl 1-(bis-(4-acetamidophenoxy)phosphoryl)-2-(4-(tert-butyloxycarbonylamino)phenyl)ethylcarbamate
• 英文别名: methyl 1-(bis(4-acetamidophenoxy)phosphoryl)-2-(4-(tert-butyloxycarbonylamino)phenyl)ethylcarbamate；tert-butyl N-[4-[2-bis(4-acetamidophenoxy)phosphoryl-2-(methoxycarbonylamino)ethyl]phenyl]carbamate
• 化学式: C₃₁H₃₇N₄O₉P
• 分子量: 640.63
• InChiKey: MMHSGJYGBUMWJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  170
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 1-(bis-(4-acetamidophenoxy)phosphoryl)-2-(4-(tert-butyloxycarbonylamino)phenyl)ethylcarbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 methyl 1-(bis(4-acetamidophenoxy)phosphoryl)-2-(4-amino-phenyl)ethylcarbamate
  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：

  、 氨基甲酸甲酯 、 tris(4-acetamidophenyl) phosphite 在 四氯化钛 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以39%的产率得到methyl 1-(bis-(4-acetamidophenoxy)phosphoryl)-2-(4-(tert-butyloxycarbonylamino)phenyl)ethylcarbamate
  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

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。
• NOVEL UROKINASE INHIBITORS
  申请人：Universiteit Antwerpen

  公开号：EP1940856B1

  公开（公告）日：2014-10-08
• US8003627B2
  申请人：——

  公开号：US8003627B2

  公开（公告）日：2011-08-23
• [EN] NOVEL UROKINASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE L'UROKINASE
  申请人：UNIV ANTWERPEN

  公开号：WO2007045496A1

  公开（公告）日：2007-04-26

  [EN] 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.
  [FR] L invention concerne de nouveaux composés possédant une activité d'inhibition sur un activateur du plasminogène de l'urokinase (uPA); des procédés de préparation des composés inhibiteurs de uPA; des compositions pharmaceutiques comprenant lesdits composés inhibiteurs de uPA; l'utilisation de ces composés inhibiteurs de uPA comme médicament et leur utilisation pour préparer un médicament permettant de traiter des états choisis dans le groupe constitué par le cancer, la croissance tumorale, l'invasion tumorale, les métastases tumorales, la rétinopathie diabétique, l'athérosclérose hémorragique et les états inflammatoires, tels que l'arthrite rhumatoïde et le psoriasis.
• 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.