3-[<1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl>-7-methoxynaphthalen-2-ylsulfonylamino]-N-propionic acid tert-butyl ester | 186551-18-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3-[<1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl>-7-methoxynaphthalen-2-ylsulfonylamino]-N-propionic acid tert-butyl ester
• 英文别名: tert-butyl 3-[[(3S)-1-[(3-cyanophenyl)methyl]-2-oxopyrrolidin-3-yl]-(7-methoxynaphthalen-2-yl)sulfonylamino]propanoate
• CAS: 186551-18-8
• 化学式: C₃₀H₃₃N₃O₆S
• 分子量: 563.675
• InChiKey: DBHUYVAUJRROMS-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  125
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-[<1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl>-7-methoxynaphthalen-2-ylsulfonylamino]-N-propionic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 3-[<1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl>-7-methoxynaphthalen-2-ylsulfonylamino]-N-propionic acid
  参考文献：
  名称：

  Design and Structure−Activity Relationships of Potent and Selective Inhibitors of Blood Coagulation Factor Xa

  摘要：

  The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (Ki = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.

  DOI：

  10.1021/jm990040h
• 作为产物：
  描述：

  [1-(3-cyanobenzyl)-2-oxopyrrolidin-3(S)-yl]carbamic acid tert-butyl ester 在 盐酸 、 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 3-[<1-(3-cyanobenzyl)-2-oxopyrrolidin-3-(S)-yl>-7-methoxynaphthalen-2-ylsulfonylamino]-N-propionic acid tert-butyl ester
  参考文献：
  名称：

  Design and Structure−Activity Relationships of Potent and Selective Inhibitors of Blood Coagulation Factor Xa

  摘要：

  The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (Ki = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.

  DOI：

  10.1021/jm990040h

文献信息

• SUBSTITUTED (SULFINIC ACID, SULFONIC ACID, SULFONYLAMINO OR SULFINYLAMINO) N- (AMINOIMINOMETHYL)PHENYLALKYL -AZAHETEROCYCLYLAMIDE COMPOUNDS
  申请人：Aventis Pharmaceuticals Inc.

  公开号：EP0853618B1

  公开（公告）日：2011-08-17
• SUBSTITUTED (SULFINIC ACID, SULFONIC ACID, SULFONYLAMINO OR SULFINYLAMINO) N- (AMINOIMINOMETHYL)PHENYLALKYL]-AZAHETEROCYCLYLAMIDE COMPOUNDS
  申请人：RHONE-POULENC RORER PHARMACEUTICALS, INC.

  公开号：EP0853618A1

  公开（公告）日：1998-07-22
• EP0853618A4
  申请人：——

  公开号：EP0853618A4

  公开（公告）日：2000-03-15
• [EN] SUBSTITUTED (SULFINIC ACID, SULFONIC ACID, SULFONYLAMINO OR SULFINYLAMINO) N-[(AMINOIMINOMETHYL)PHENYLALKYL]-AZAHETEROCYCLYLAMIDE COMPOUNDS<br/>[FR] COMPOSES D'(ACIDE SULFINIQUE, ACIDE SULFONIQUE, SULFONYLAMINO OU SULFINYLAMINO) N-[(AMINOIMINOMETHYL)PHENYLALKYL]-AZAHETEROCYCLYLAMIDE SUBSTITUES
  申请人：RHÔNE-POULENC RORER PHARMACEUTICALS INC.

  公开号：WO1996040679A1

  公开（公告）日：1996-12-19

  (EN) The compounds of formula (I) exhibit useful pharmacological activity and accordingly are incorporated into pharmaceutical compositions and used in the treatment of patients suffering from certain medical disorders. More especially, they are inhibitors of the activity of Factor Xa. The present invention is directed to compounds of formula (I), compositions containing compounds of formula (I), and their use, which are for treating a patient suffering from, or subject to, physiological condition which can be ameliorated by the administration of an inhibitor of the activity of Factor Xa.(FR) Les composés de formule (I) présentent une utilité pharmacologique et, de ce fait, on les incorpore dans des compositions pharmaceutiques et on les utilise dans le traitement de patients souffrant de certains troubles médicaux. Ils sont, plus particulièrement, des inhibiteurs de l'activité du Facteur Xa. L'invention concerne des composés de formule (I), des compositions contenant lesdits composés, ainsi que leur utilisation dans le traitement de patients souffrant d'états physiologiques, ou sujets à ces états, qu'on peut améliorer par administration d'un inhibiteur de l'activité du Facteur Xa.
• Design and Structure−Activity Relationships of Potent and Selective Inhibitors of Blood Coagulation Factor Xa
  作者：William R. Ewing、Michael R. Becker、Vincent E. Manetta、Roderick S. Davis、Henry W. Pauls、Helen Mason、Yong Mi Choi-Sledeski、Daniel Green、Don Cha、Alfred P. Spada、Daniel L. Cheney、Jonathan S. Mason、Sebastien Maignan、Jean-Pierre Guilloteau、Karen Brown、Dennis Colussi、Ross Bentley、Jeff Bostwick、Charles J. Kasiewski、Suzanne R. Morgan、Robert J. Leadley、Christopher T. Dunwiddie、Mark H. Perrone、Valeria Chu

  DOI：10.1021/jm990040h

  日期：1999.9.1

  The discovery of a series of non-peptide factor Xa (FXa) inhibitors incorporating 3-(S)-amino-2-pyrrolidinone as a central template is described. After identifying compound 4, improvements in in vitro potency involved modifications of the liphophilic group and optimizing the angle of presentation of the amidine group to the S1 pocket of FXa. These studies ultimately led to compound RPR120844, a potent inhibitor of FXa (Ki = 7 nM) which shows selectivity for FXa over trypsin, thrombin, and several fibrinolytic serine proteinases. RPR120844 is an effective anticoagulant in both the rat model of FeCl2-induced carotid artery thrombosis and the rabbit model of jugular vein thrombus formation.