2-Chloro-3-(2-oxopiperidin-1-YL)benzene-1-sulfonyl chloride | 1509935-78-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 2-Chloro-3-(2-oxopiperidin-1-YL)benzene-1-sulfonyl chloride
• 英文别名: 2-chloro-3-(2-oxopiperidin-1-yl)benzenesulfonyl chloride
• CAS: 1509935-78-7
• 化学式: C₁₁H₁₁Cl₂NO₃S
• 分子量: 308.185
• InChiKey: WBORAMORNOWMGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-溴-2-氯-3-氟苯 在 copper(l) iodide 、 磺酰氯 、 四甲基乙二胺 、 potassium carbonate 、 caesium carbonate 、 溶剂黄146 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 24.75h， 生成 2-Chloro-3-(2-oxopiperidin-1-YL)benzene-1-sulfonyl chloride
  参考文献：
  名称：

  5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor

  摘要：

  Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 mu M, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene PI fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with K-i's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 mu M) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.

  DOI：

  10.1021/jm4005835

文献信息

• 5-Chlorothiophene-2-carboxylic Acid [(<i>S</i>)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor
  作者：Jerome Meneyrol、Markus Follmann、Gilbert Lassalle、Volkmar Wehner、Guillaume Barre、Tristan Rousseaux、Jean-Michel Altenburger、Frederic Petit、Zsolt Bocskei、Herman Schreuder、Nathalie Alet、Jean-Pascal Herault、Laurence Millet、Frederique Dol、Peter Florian、Paul Schaeffer、Freddy Sadoun、Sylvie Klieber、Christophe Briot、Françoise Bono、Jean-Marc Herbert

  DOI：10.1021/jm4005835

  日期：2013.12.12

  Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 mu M, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene PI fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with K-i's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 mu M) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.