N-(5-氯吡啶-2-基)-5-氯-2-硝基苯甲酰胺 | 280771-82-6

• 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-(5-氯吡啶-2-基)-5-氯-2-硝基苯甲酰胺
• 英文名称: 5-chloro-N-(5-chloropyridin-2-yl)-2-nitrobenzamide
• 英文别名: N-(5-chloropyridin-2-yl)-5-chloro-2-nitrobenzamide；N-(5-chloropyridine-2-yl)-5-chloro-2-nitrobenzamide；5-Chloro-N-(5-chloro-pyridin-2-yl)-2-nitro-benzamide
• CAS: 280771-82-6
• 化学式: C₁₂H₇Cl₂N₃O₃
• 分子量: 312.112
• InChiKey: DQSJZRHQVGCCRH-UHFFFAOYSA-N

物化性质

• 沸点：
  407.7±45.0 °C(Predicted)
• 密度：
  1.582±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(5-氯吡啶-2-基)-5-氯-2-硝基苯甲酰胺 在 sodium tetrahydroborate 、 tin(II) chloride dihdyrate 、 四溴化碳 、 硫酸 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 2-(4-(N-(2-bromoethyl)-S-methylsulfonimidoyl)benzamido)-5-chloro-N-(5-chloropyridin-2-yl)benzamide
  参考文献：
  名称：

  Synthesis and structure–activity relationship of potent, selective and orally active anthranilamide-based factor Xa inhibitors: Application of weakly basic sulfoximine group as novel S4 binding element

  摘要：

  A novel series of potent and efficacious factor Xa inhibitors which possesses sulfoximine moiety as novel S4 binding element in anthranilamide chemotype has been identified. Lead optimization at this novel P4 group led to many potent factor Xa inhibitors with excellent anticoagulant activity in human plasma. Selected compounds were dosed orally in rats and checked for their ex vivo prothrombin time prolonging activity, which resulted in identification of compound 5-chloro-N-(5-chloropyridin-2-yl)-2-(4-(N-(2(diethylamino)acetyl)-S-methylsulfonimidoyl)benzamido)benzamide (18f). The detailed pharmacokinetic evaluation and subsequent metabolism study of 181 suggested the presence of an active metabolite. The compound 18f and its active metabolite 18b demonstrated excellent in vivo efficacy in both arterial and venous thrombosis model in rats and were found to be highly selective against related serine proteases. Based on this promising profile, compound 18f was selected for further evaluation. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.10.005
• 作为产物：
  描述：

  5-氯-2-硝基苯甲酸 在 4-二甲氨基吡啶 吡啶 、 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 生成 N-(5-氯吡啶-2-基)-5-氯-2-硝基苯甲酰胺
  参考文献：
  名称：

  Thiophene-Anthranilamides as Highly Potent and Orally Available Factor Xa Inhibitors

  摘要：

  There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the subject of intensive drug discovery efforts. Investigation of a hit from high-throughput screening identified a series of thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation of hydrophilic groups led to the discovery of compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant activity. Based on their high potency, selectivity, oral pharmacokinetics, and efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b), ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.

  DOI：

  10.1021/jm070125f

文献信息

• Aromatic amides
  申请人：Eli Lilly and Company

  公开号：US06635657B1

  公开（公告）日：2003-10-21

  This application relates to a compound of formula I (or a pharmaceutically acceptable salt 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.

  本申请涉及式I化合物（或其药用可接受的盐），如本文所述，其药物组合物，及其作为因子Xa抑制剂的用途，以及其制备过程和中间体。
• SULFOXIMINE DERIVATIVES AS FACTOR XA INHIBITORS
  申请人：Pandya Vrajesh B.

  公开号：US20110065717A1

  公开（公告）日：2011-03-17

  The present invention relates to novel substituted sulfoximine derivatives of the general formula (I), their tautomeric forms, their stereoisomers, their pharmaceutically acceptable salts, pharmaceutical compositions containing them, methods for their preparation, use of these compounds in medicine and the intermediates involved in their preparation.

  本发明涉及一种新型的通式（I）的取代砜肟衍生物，其互变异构体，立体异构体，药学上可接受的盐，含有它们的药物组合物，它们的制备方法，这些化合物在医学上的应用以及其制备中涉及的中间体。
• LACTAM-CONTAINING COMPOUNDS AND DERIVATIVES THEREOF AS FACTOR XA INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：US20170050964A1

  公开（公告）日：2017-02-23

  The present application describes lactam-containing compounds and derivatives thereof of Formula I: P 4 —P-M-M 4 I or pharmaceutically acceptable salt forms thereof, wherein ring P, if present is a 5-7 membered carbocycle or heterocycle and ring M is a 5-7 membered carbocycle or heterocycle. Compounds of the present invention are useful as inhibitors of trypsin-like serine proteases, specifically factor Xa.

  本申请描述了公式I中含有内酰胺的化合物及其衍生物：P4—P-M-M4I或其药用盐形式，其中环P（如果存在）是一个5-7成员的碳环或杂环，环M是一个5-7成员的碳环或杂环。本发明的化合物可用作胰蛋白酶样丝氨酸蛋白酶的抑制剂，特别是因子Xa。
• Substituted heterocyclic amides
  申请人：——

  公开号：US20040097491A1

  公开（公告）日：2004-05-20

  This application relates to a compound of formula (I) (or a pharmaceutically acceptable salt 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.

  该申请涉及到式（I）的化合物（或其药用可接受的盐），如本文所定义，其药物组成，以及其作为因子Xa抑制剂的用途，以及其制备方法和中间体。
• [EN] AROMATIC AMIDES<br/>[FR] AMIDES AROMATIQUES
  申请人：LILLY CO ELI

  公开号：WO2000039118A1

  公开（公告）日：2000-07-06

  This application relates to a compound of formula I (or a pharmaceutically acceptable salt 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.

  本申请涉及公式 I 的化合物（或其药学上可接受的盐），其制药组合物以及其作为因子 Xa 抑制剂的用途，以及其制备过程和中间体。