2-amino-N-(5-chloro-2-pyridinyl)-3-methoxybenzamide | 229342-63-6

• 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: 2-amino-N-(5-chloro-2-pyridinyl)-3-methoxybenzamide
• 英文别名: 2-amino-N-(5-chloropyridin-2-yl)-3-methoxybenzamide；N-(5-chloropyridin-2-yl)-2-amino-3-methoxybenzamide
• CAS: 229342-63-6
• 化学式: C₁₃H₁₂ClN₃O₂
• 分子量: 277.71
• InChiKey: QCQOICSMAQPPOQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  77.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-amino-N-(5-chloro-2-pyridinyl)-3-methoxybenzamide 在 N-氯代丁二酰亚胺 、 硫酸 、 三乙胺 、 potassium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 40.0h， 生成 5-chloro-N-(5-chloropyridin-2-yl)-2-[[4-[N-[2-(diethylamino)acetyl]-S-methylsulfonimidoyl]benzoyl]amino]-3-methoxybenzamide
  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：

  3-甲氧基-2-硝基苯甲酰氯 在 4-二甲氨基吡啶 吡啶 、 sodium disulfite 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 2-amino-N-(5-chloro-2-pyridinyl)-3-methoxybenzamide
  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。
• Quaternary amidino based inhibitors of factor xa
  申请人：——

  公开号：US20040077690A1

  公开（公告）日：2004-04-22

  Novel quaternary amidino-containing compounds of the general formulae (I), (II), (III), (IV), (V) and (VI): including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and the compositions are useful in vitro or in vivo for preventing or treating conditions in mammals characterized by undesired thrombosis. 1 2

  描述了具有一般式(I)、(II)、(III)、(IV)、(V)和(VI)的新颖含四元氮基的化合物，包括它们的药学上可接受的同分异构体、盐、水合物、溶剂合物和前药衍生物，具有对哺乳动物凝血因子Xa活性。还描述了含有这些化合物的组合物。这些化合物和组合物在体外或体内用于预防或治疗哺乳动物中由不良血栓形成所特征的疾病。
• [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。
• Ortho-anthranilamide derivatives as anti-coagulants
  申请人：Berlex Laboratories, Inc.

  公开号：US06498185B1

  公开（公告）日：2002-12-24

  This invention is directed to compounds of formula (III): wherein B, C, D, E, R1, R2 and R3 are disclosed herein. These compounds are disclosed as being useful as anti coagulants.

  本发明涉及式（III）化合物：其中B，C，D，E，R1，R2和R3在此披露。这些化合物被披露为有用的抗凝剂。