N-(2-氨基苯基)-4-叔丁基苯甲酰胺 | 219492-28-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(2-氨基苯基)-4-叔丁基苯甲酰胺
• 中文别名: N-（2-氨基苯基）-4-叔丁基苯甲酰胺
• 英文名称: N-(2-aminophenyl)-4-(1,1-dimethylethyl)-benzamide
• 英文别名: N¹-(4-tert-butylbenzoyl)-1,2-benzenediamine；N1-(4-tert-butylbenzoyl)-1,2-benzenediamine；N2-(4-t-butylbenzoyl)-1,2-benzenediamine；2-(4-t-butylbenzoylamino)aniline；N-(2-aminophenyl)-4-tert-butylbenzamide
• CAS: 219492-28-1
• 化学式: C₁₇H₂₀N₂O
• mdl: MFCD02585708
• 分子量: 268.359
• InChiKey: WNUQREGTGZRIBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.235
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  N-(2-氨基苯基)-4-叔丁基苯甲酰胺 在 5percent Pd/C 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 24.0h， 生成 N-[2-[(4-tert-butylbenzoyl)amino]phenyl]-1-carbamimidoylpiperidine-3-carboxamide
  参考文献：
  名称：

  Structure-Based Design of Potent, Amidine-Derived Inhibitors of Factor Xa:  Evaluation of Selectivity, Anticoagulant Activity, and Antithrombotic Activity

  摘要：

  To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of Ma to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in Ma affinity and a refined model of the new inhibitors in the Ma active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of Ma relative to other trypsin-like serine proteases. Furthermore, the Ma affinity of compounds in this series (K-ass = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.

  DOI：

  10.1021/jm9903287
• 作为产物：
  描述：

  对叔丁基苯甲酰氯 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 生成 N-(2-氨基苯基)-4-叔丁基苯甲酰胺
  参考文献：
  名称：

  Structure-Based Design of Potent, Amidine-Derived Inhibitors of Factor Xa:  Evaluation of Selectivity, Anticoagulant Activity, and Antithrombotic Activity

  摘要：

  To enhance the potency of 1,2-dibenzamidobenzene-derived inhibitors of factor Xa (fXa), an amidine substituent was incorporated on one of the benzoyl side chains to interact with Asp189 in the S1 specificity pocket. Lead molecule 1 was docked into the active site of Ma to facilitate inhibitor design. Subsequently, iterative SAR studies and molecular modeling led to a 1000-fold increase in Ma affinity and a refined model of the new inhibitors in the Ma active site. Strong support for the computational model was achieved through the acquisition of an X-ray crystal structure using thrombin as a surrogate protein. The amidines in this series show high levels of selectivity for the inhibition of Ma relative to other trypsin-like serine proteases. Furthermore, the Ma affinity of compounds in this series (K-ass = 50-500 x 10(6) L/mol) translates effectively into both anticoagulant activity in vitro and antithrombotic activity in vivo.

  DOI：

  10.1021/jm9903287

文献信息

• Antithrombotic agents
  申请人：Eli Lilly and Company

  公开号：US06313122B1

  公开（公告）日：2001-11-06

  This application relates to a compound of formula (I), a pharmaceutically acceptable salt of the compound, or a prodrug thereof, as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.

  这项申请涉及到式(I)的化合物，该化合物的药用盐或其前药，如本文所定义，以及其药物组合物，以及其作为Xa因子抑制剂的用途，以及其制备方法和中间体。
• [EN] ANTITHROMBOTIC AGENTS<br/>[FR] AGENTS ANTITHROMBOTIQUES
  申请人：ELI LILLY AND COMPANY

  公开号：WO1999000121A1

  公开（公告）日：1999-01-07

  (EN) This application relates to a compound of formula (I) (or a prodrug thereof or a pharmaceutically acceptable salt of the compound or prodrug thereof) as defined herein, pharmaceutical compositions thereof, and its use as an inhibitor of factor Xa, as well as a process for its preparation and intermediates therefor.(FR) Cette invention traite d'un composé de la formule (I), telle que définie dans le descriptif, (ou bien d'un promédicament de ce composé ou bien d'un sel pharmaceutiquement acceptable de ce composé ou d'un promédicament de ce composé), de compositions pharmaceutiques contenant ce composé, de l'utilisation de ce composé en tant qu'inhibiteur du facteur Xa, d'un procédé permettant de préparer ce composé et d'intermédiaires utilisés pour produire ledit composé.

  该申请涉及公式（I）的化合物（或其前药或化合物或前药的药学上可接受的盐），其药物组成，以及其作为因子Xa的抑制剂的用途，以及其制备过程和中间体。
• PhNCO-enabled synthesis of secondary amides from <i>N</i>-(2-aminophenyl)benzamides
  作者：Karthick Govindan、Nian-Qi Chen、Alageswaran Jayaram、Wei-Yu Lin

  DOI：10.1039/d3nj04995g

  日期：——

  We have successfully developed an efficient method for synthesizing secondary amides utilizing easily accessible N-(2-aminophenyl)benzamide and phenyl isocyanate. Notably, the leaving group can be easily recuperated as a carbonylated N-heterocycle, which holds notable relevance in pharmaceutical applications. The crux of this strategy involves a sequential nucleophilic/intramolecular addition process

  我们成功开发了一种利用容易获得的N- (2-氨基苯基)苯甲酰胺和异氰酸苯酯合成仲酰胺的有效方法。值得注意的是，离去基团可以很容易地恢复为羰基化的N-杂环，这在制药应用中具有显着的相关性。该策略的关键涉及异氰酸苯酯的连续亲核/分子内加成过程，然后进行转酰胺基化。此外，该方案还具有原子经济性、实用性、一锅两步反应以及底物制备简便等特点。
• 1,2-Dibenzamidobenzene Inhibitors of Human Factor Xa
  作者：David K. Herron、Theodore Goodson、Michael R. Wiley、Leonard C. Weir、Jeffrey A. Kyle、Ying K. Yee、Ann Louise Tebbe、Jennifer M. Tinsley、David Mendel、John J. Masters、Jeffry B. Franciskovich、J. Scott Sawyer、Douglas W. Beight、Andrew M. Ratz、Guy Milot、Steven E. Hall、Valentine J. Klimkowski、James H. Wikel、Brian J. Eastwood、Richard D. Towner、Donetta S. Gifford-Moore、Trelia J. Craft、Gerald F. Smith

  DOI：10.1021/jm990326m

  日期：2000.3.1

  High-throughput screening of a combinatorial library of diamidophenols yielded lead compounds with the ability to inhibit human factor Xa (fXa) at micromolar concentrations (e.g. compound 4, fXa apparent K-ass = 0.64 x 10(6) L/mol). SAR studies in this novel structural series of fXa inhibitors showed that the phenolic hydroxyl group was not essential for activity. The best activity was found in substituted 1,2-dibenzamidobenzenes in which the phenyl group of one benzoyl group (A-ring) was substituted in the 4-position with relatively small lipophilic or polarizable groups such as methoxy, vinyl, or chloro and the phenyl group of the other benzoyl group (B-ring) was substituted in the 4-position with larger lipophilic groups such as tert-butyl or dimethylamino. The central phenyl ring (C-ring) tolerated a wide variety of substituents, but methoxy, methanesulfonamido, hydroxyl, and carboxyl substitution produced slightly higher levels of activity than other substituents when present in combination with favorable B-ring substitution. Methylation of the amide nitrogen atoms was found to greatly decrease activity. Compound 12 is the highest affinity fXa inhibitor in this group of compounds, having fXa apparent K-ass = 25.5 x 10(6) L/mol, about 40x more active than the original lead. This lead series does not show potent inhibition of human thrombin. A model for the binding of these ligands to the fXa active site is proposed. The model is consistent with the observed SAR and can serve to guide future SAR studies.
• Phenylamide - Verfahren zu ihrer Herstellung sowie diese Verbindungen enthaltende Arzneimittel
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0358118B1

  公开（公告）日：1994-03-16