2-amino-5-chloro-N-(5-chloropyridin-2-yl)-3-methoxybenzamide | 229342-88-5

• 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-5-chloro-N-(5-chloropyridin-2-yl)-3-methoxybenzamide
• 英文别名: N-(5-chloropyridin-2-yl)-2-amino-3-methoxy-5-chlorobenzamide
• CAS: 229342-88-5
• 化学式: C₁₃H₁₁Cl₂N₃O₂
• 分子量: 312.155
• InChiKey: BCBYUUHJWCPHOO-UHFFFAOYSA-N

物化性质

• 熔点：
  146-148 °C(Solv: benzene (71-43-2))
• 沸点：
  426.3±45.0 °C(Predicted)
• 密度：
  1.474±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：
  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-5-chloro-N-(5-chloropyridin-2-yl)-3-methoxybenzamide 在 吡啶 、 sodium acetate 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 5.0h， 生成 N-(5-chloropyridin-2-yl)-2-[((4-((2-imino-tetrahydroimidazol-1-yl)methyl)-3-chlorothiophen-2-yl)carbonyl)amino]-3-methoxy-5-chlorobenzamide
  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
• 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 、 N-氯代丁二酰亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 苯 为溶剂， 反应 24.0h， 生成 2-amino-5-chloro-N-(5-chloropyridin-2-yl)-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

• Lactam-containing compounds and derivatives thereof as factor Xa inhibitors
  申请人：——

  公开号：US20030191115A1

  公开（公告）日：2003-10-09

  The present application describes lactam-containing compounds and derivatives thereof of Formula I: 1 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.

  本申请描述了具有Formula I的内酰胺含有化合物及其衍生物，或其药用可接受的盐形式，其中环P（如存在）是一个5-7成员碳环或杂环，环M是一个5-7成员碳环或杂环。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。
• 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。
• Ortho-anthranilamide derivatives as anti-coagulants
  申请人：Berlex Laboratories, Inc.

  公开号：US06140351A1

  公开（公告）日：2000-10-31

  This invention is directed to compounds of formula (III): ##STR1## wherein B, C, D, E, R.sup.1, R.sup.2 and R.sup.3 are disclosed herein. These compounds are disclosed as being useful as anti-coagulants.

  这项发明涉及到化合物的公式（III）：##STR1## 其中B、C、D、E、R.sup.1、R.sup.2和R.sup.3在本文中有披露。这些化合物被披露为抗凝血剂。
• 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。
• Lactam-containing compounds and derivatives thereof as factor xa inhibitors
  申请人：Pinto J.P. Donald

  公开号：US20050267097A1

  公开（公告）日：2005-12-01

  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中含有内酰胺化合物及其衍生物，或其药学上可接受的盐形式，其中环P（如存在）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的抑制剂。