3,5-diamino-N-[(E,2R)-1-(3,4-dichlorophenyl)-5-oxo-5-[[(3R)-2-oxoazepan-3-yl]amino]pent-3-en-2-yl]-N-methylbenzamide | 932041-32-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3,5-diamino-N-[(E,2R)-1-(3,4-dichlorophenyl)-5-oxo-5-[[(3R)-2-oxoazepan-3-yl]amino]pent-3-en-2-yl]-N-methylbenzamide
• CAS: 932041-32-2
• 化学式: C₂₅H₂₉Cl₂N₅O₃
• 分子量: 518.443
• InChiKey: WQLBGKLFIYNVQZ-WVDRJWPYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  131
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3,5-diamino-N-[(E,2R)-1-(3,4-dichlorophenyl)-5-oxo-5-[[(3R)-2-oxoazepan-3-yl]amino]pent-3-en-2-yl]-N-methylbenzamide 以 二氯甲烷 为溶剂， 生成 O-methyl N-[3-[[(E,2R)-1-(3,4-dichlorophenyl)-5-oxo-5-[[(3R)-2-oxoazepan-3-yl]amino]pent-3-en-2-yl]-methylcarbamoyl]-5-(methoxycarbothioylamino)phenyl]carbamothioate
  参考文献：
  名称：

  Design and synthesis of 3,5-disubstituted benzamide analogues of DNK333 as dual NK1/NK2 receptor probes

  摘要：

  N-[(R, R)-(E)-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3, 5-bis(trifluoromethyl)benzamide (DNK333, 1b) has been reported to be a potent and balanced dual neurokinin (tachykinin) receptor antagonist. A recent clinical trial using DNK333 has shown that it blocks the NKA-induced bronchoconstriction in patients with asthma. A series of six analogues 3-8 derived from modification of 3,5-bis(trifluoromethyl)benzamide moiety of DNK333 has been synthesized to serve as the dual NK,/NKz receptor probes. The 3,5-dinitro substituted benzamide compound 3 was found to possess potent and balanced dual NK,/NK2 receptor antagonist activities (pK(b) = 8.4 for the NK1 receptors, pK(b) = 7.87 for the NK2 receptors) in the functional assay using guinea pig trachea. Furthermore, SAR analysis suggests that steric, electronic, and lipophilic characteristics of substituents in the benzamide region of DNK333 have a crucial effect on both the NKI and NK2 receptor antagonist activities. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.064
• 作为产物：
  描述：

  (E)-(R)-5-(3,4-dichlorophenyl)-4-methylaminopent-2-enoic acid (R)-(2-oxoazepan-3-yl)amide 在 碳酸氢钠 、 锌 、 hydrazinium monoformate 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.0h， 生成 3,5-diamino-N-[(E,2R)-1-(3,4-dichlorophenyl)-5-oxo-5-[[(3R)-2-oxoazepan-3-yl]amino]pent-3-en-2-yl]-N-methylbenzamide
  参考文献：
  名称：

  Design and synthesis of 3,5-disubstituted benzamide analogues of DNK333 as dual NK1/NK2 receptor probes

  摘要：

  N-[(R, R)-(E)-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3, 5-bis(trifluoromethyl)benzamide (DNK333, 1b) has been reported to be a potent and balanced dual neurokinin (tachykinin) receptor antagonist. A recent clinical trial using DNK333 has shown that it blocks the NKA-induced bronchoconstriction in patients with asthma. A series of six analogues 3-8 derived from modification of 3,5-bis(trifluoromethyl)benzamide moiety of DNK333 has been synthesized to serve as the dual NK,/NKz receptor probes. The 3,5-dinitro substituted benzamide compound 3 was found to possess potent and balanced dual NK,/NK2 receptor antagonist activities (pK(b) = 8.4 for the NK1 receptors, pK(b) = 7.87 for the NK2 receptors) in the functional assay using guinea pig trachea. Furthermore, SAR analysis suggests that steric, electronic, and lipophilic characteristics of substituents in the benzamide region of DNK333 have a crucial effect on both the NKI and NK2 receptor antagonist activities. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.064

文献信息

• Design and synthesis of 3,5-disubstituted benzamide analogues of DNK333 as dual NK1/NK2 receptor probes
  作者：Venkat Manoj Swarna、Bradley J. Undem、Vijaya L. Korlipara

  DOI：10.1016/j.bmcl.2006.11.064

  日期：2007.2

  N-[(R, R)-(E)-(3,4-dichlorobenzyl)-3-(2-oxoazepan-3-yl)carbamoyl]allyl-N-methyl-3, 5-bis(trifluoromethyl)benzamide (DNK333, 1b) has been reported to be a potent and balanced dual neurokinin (tachykinin) receptor antagonist. A recent clinical trial using DNK333 has shown that it blocks the NKA-induced bronchoconstriction in patients with asthma. A series of six analogues 3-8 derived from modification of 3,5-bis(trifluoromethyl)benzamide moiety of DNK333 has been synthesized to serve as the dual NK,/NKz receptor probes. The 3,5-dinitro substituted benzamide compound 3 was found to possess potent and balanced dual NK,/NK2 receptor antagonist activities (pK(b) = 8.4 for the NK1 receptors, pK(b) = 7.87 for the NK2 receptors) in the functional assay using guinea pig trachea. Furthermore, SAR analysis suggests that steric, electronic, and lipophilic characteristics of substituents in the benzamide region of DNK333 have a crucial effect on both the NKI and NK2 receptor antagonist activities. (c) 2006 Elsevier Ltd. All rights reserved.