(R)-4-chloro-2-fluoro-N-(2-fluorophenyl)-N-methyl-5-(octahydropyrrolo[1,2-a]pyrazine-2-carbonyl)benzenesulfonamide | 1235560-83-4

• 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: (R)-4-chloro-2-fluoro-N-(2-fluorophenyl)-N-methyl-5-(octahydropyrrolo[1,2-a]pyrazine-2-carbonyl)benzenesulfonamide
• 英文别名: 4-chloro-2-fluoro-N-(2-fluorophenyl)-5-[(8aR)-hexahydropyrrolo[1,2-a]pyrazin-2(1H)-ylcarbonyl]-N-methylbenzenesulfonamide；5-[(8aR)-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-2-carbonyl]-4-chloro-2-fluoro-N-(2-fluorophenyl)-N-methylbenzenesulfonamide
• CAS: 1235560-83-4
• 化学式: C₂₁H₂₂ClF₂N₃O₃S
• 分子量: 469.94
• InChiKey: SZDJXSZWBRYRNN-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  69.3
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氯-5-(氯磺酰)-4-氟苯甲酰氯化 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 (R)-4-chloro-2-fluoro-N-(2-fluorophenyl)-N-methyl-5-(octahydropyrrolo[1,2-a]pyrazine-2-carbonyl)benzenesulfonamide
  参考文献：
  名称：

  Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639

  摘要：

  The discovery of a novel peripherally acting and selective Ca(v)3.2 T-type calcium channel blocker, ABT-639, is described. HTS hits 1 and 2, which have poor metabolic stability, were optimized to obtain 4, which has improved stability and oral bioavailability. Modification of 4 to further improve ADME properties led to the discovery of ABT-639. Following oral administration, ABT-639 produces robust antinociceptive activity in experimental pain models at doses that do not significantly alter psychomotor or hemodynamic function in the rat.

  DOI：

  10.1021/acsmedchemlett.5b00023

文献信息

• NOVEL BENZENESULFONAMIDES AS CALCIUM CHANNEL BLOCKERS
  申请人：Zhang Qingwei

  公开号：US20100197693A1

  公开（公告）日：2010-08-05

  The present application relates to calcium channel inhibitors comprising compounds of formula (I), formula (II), formula (III), or formula (IV), wherein L 1 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 and R c are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.

  本申请涉及到含有式(I)、式(II)、式(III)或式(IV) 化合物的钙通道抑制剂，其中L1、R1、R2、R3、R4、R5、R6、R7和R8在说明书中有定义。本申请还涉及到包含这些化合物的组合物，以及使用这些化合物和组合物治疗疾病和病症的方法。
• US8101614B2
  申请人：——

  公开号：US8101614B2

  公开（公告）日：2012-01-24
• US8741899B2
  申请人：——

  公开号：US8741899B2

  公开（公告）日：2014-06-03
• Optimization of ADME Properties for Sulfonamides Leading to the Discovery of a T-Type Calcium Channel Blocker, ABT-639
  作者：Qingwei Zhang、Zhiren Xia、Shailen Joshi、Victoria E. Scott、Michael F. Jarvis

  DOI：10.1021/acsmedchemlett.5b00023

  日期：2015.6.11

  The discovery of a novel peripherally acting and selective Ca(v)3.2 T-type calcium channel blocker, ABT-639, is described. HTS hits 1 and 2, which have poor metabolic stability, were optimized to obtain 4, which has improved stability and oral bioavailability. Modification of 4 to further improve ADME properties led to the discovery of ABT-639. Following oral administration, ABT-639 produces robust antinociceptive activity in experimental pain models at doses that do not significantly alter psychomotor or hemodynamic function in the rat.