(S)-3-(4-cyanophenyl)-N-cyclopentyl-N-methyl-2-(6, 7-dimethoxy-naphthalene-2-sulfonylamino)-propionamide | 184771-56-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (S)-3-(4-cyanophenyl)-N-cyclopentyl-N-methyl-2-(6, 7-dimethoxy-naphthalene-2-sulfonylamino)-propionamide
• 英文别名: (2S)-3-(4-cyanophenyl)-N-cyclopentyl-2-[(6,7-dimethoxynaphthalen-2-yl)sulfonylamino]-N-methylpropanamide
• CAS: 184771-56-0
• 化学式: C₂₈H₃₁N₃O₅S
• 分子量: 521.637
• InChiKey: XZTBJYFLLINDBJ-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-3-(4-cyanophenyl)-N-cyclopentyl-N-methyl-2-(6, 7-dimethoxy-naphthalene-2-sulfonylamino)-propionamide 在 硫化氢 、 一水合肼 作用下， 以 吡啶 、 甲醇 、 乙腈 为溶剂， 反应 49.0h， 生成
  参考文献：
  名称：

  Structural Modification of an Orally Active Thrombin Inhibitor, LB30057: Replacement of the D-Pocket-binding Naphthyl Moiety

  摘要：

  An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (K-i = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (K-i = 0.045 nM). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00044-3
• 作为产物：
  描述：

  (2S)-2-(N-tert-butoxycarbonyl)-amino-N-cyclopentyl-3-(4-cyanophenyl)-N-methylpropanamide 在 N-甲基吗啉 、 乙酰氯 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (S)-3-(4-cyanophenyl)-N-cyclopentyl-N-methyl-2-(6, 7-dimethoxy-naphthalene-2-sulfonylamino)-propionamide
  参考文献：
  名称：

  Structural Modification of an Orally Active Thrombin Inhibitor, LB30057: Replacement of the D-Pocket-binding Naphthyl Moiety

  摘要：

  An amidrazonophenylalanine derivative LB30057 (2) was identified as a potent (K-i = 0.38 nM), selective, and orally active thrombin inhibitor. As a continuation of studies into benzamidrazone-based thrombin inhibitors, we have structurally modified compound 2 by replacing the naphthyl group with a variety of hydrophobic moieties. This study led to discovery of several compounds with significantly enhanced potency in thrombin inhibition without sacrificing selectivity against trypsin and oral absorption. The highest activity was obtained with compound 23 (K-i = 0.045 nM). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00044-3

文献信息

• Selective thrombin inhibitors
  申请人：LG Chemical Limited

  公开号：EP0739886B1

  公开（公告）日：2003-10-01
• US5747535A
  申请人：——

  公开号：US5747535A

  公开（公告）日：1998-05-05
• US5977114A
  申请人：——

  公开号：US5977114A

  公开（公告）日：1999-11-02
• US5985899A
  申请人：——

  公开号：US5985899A

  公开（公告）日：1999-11-16
• [EN] SELECTIVE THROMBIN INHIBITORS<br/>[FR] INHIBITEURS SELECTIFS DE THROMBINE
  申请人：LG CHEMICAL LTD.

  公开号：WO1997049673A1

  公开（公告）日：1997-12-31

  (EN) The present invention relates to a novel selective thrombin inhibitor having formula (I), which is also effective by oral administration, in which R1 represents acetyl substituted with aryl or aryloxy, or represents sulfonyl substituted with substituted or unsubstituted aryl or N-containing heterocyclic group, X represents a group of formula (a) or (b), R2 and R3 independently of one another represent hydrogen; cycloalkyl substituted or unsubstituted with carboxyl or alkoxycarbonyl; arylalkyloxy; hydroxy; or lower alkyl substituted or unsubstituted with carboxyl, alkoxycarbonyl or hydroxy, or R2 and R3 together with nitrogen atom to which they are attached can form a piperidine group substituted with carboxyl or alkoxycarbonyl, R4 represents hydrogen, lower alkyl or lower alkoxy, R5 represents alkanesulfonyl; alkoxycarbonyl; alkylcarbonyl; formyl; lower alkyl; aryl substituted or unsubstituted with alkoxy or haloalkyl; or hydroxy-substituted lower alkyl, and R6 and R7 independently of one another represent hydrogen, lower alkyl or amino, and to a process for preparation thereof and a pharmaceutical composition for thrombin inhibition which comprises the compound of formula (I) as an active ingredient.(FR) Nouvel inhibiteur sélectif de thrombine de formule (I), également efficace lorsqu'il est administré oralement. Dans la formule (I), R1 représente acétyle à substitution aryle ou aryloxy, ou représente sulfonyle substitué par aryle ou par groupe hétérocyclique contenant N substitués ou non substitués, X représente un groupe de formule (a) ou (b), R2 et R3 indépendamment l'un de l'autre représentent hydrogène; cycloalkyle substitué ou non substitué par carboxyle ou alcoxycarbonyle; arylalkyloxy; hydroxy; ou alkyle inférieur substitué ou non substitué par carboxyle, alcoxycarbonyle ou hydroxy ou R2 et R3 avec l'atome d'azote auquel ils sont liés peut former un groupe pipéridine à substitution carboxyle ou alcoxycarbonyle, R4 représente hydrogène, alkyle inférieur ou alcoxy inférieur, R5 représente alcanesulfonyle; alcoxycarbonyle; alkylcarbonyle; formyle; alkyle inférieur; aryle substitué ou non substitué par alcoxy ou haloalkyle; ou alkyle inférieur à substitution hydroxy et R6 et R7 indépendamment l'un de l'autre représentent hydrogène, alkyle inférieur ou amino. La présente invention concerne également un procédé de préparation dudit inhibiteur et une composition pharmaceutique pour l'inhibition de la thrombine qui comporte le composé de formule (I) en tant qu'ingrédient actif.