(S)-VSN16

• 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: (S)-VSN16
• 英文别名: 3-[(Z)-6-(dimethylamino)-6-oxohex-1-enyl]-N-[(2S)-1-hydroxypropan-2-yl]benzamide
• 化学式: C₁₈H₂₆N₂O₃
• 分子量: 318.416
• InChiKey: SVYRYFAUQHVGAI-PODYEWJSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-(6-(dimethylamino)-6-oxohex-1-yn-1-yl)benzoic acid 、 L-氨基丙醇 在 palladium on barium sulfate (5percent) 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 喹啉 、 氢气 作用下， 以 二氯甲烷 、 三乙胺 、 甲醇 为溶剂， 以60.7%的产率得到(S)-VSN16
  参考文献：
  名称：

  Vascular pharmacology of a novel cannabinoid-like compound, 3-(5-dimethylcarbamoyl-pent-1-enyl)-N -(2-hydroxy-1-methyl-ethyl)benzamide (VSN16) in the rat

  摘要：

  Background and purpose:A putative novel cannabinoid receptor mediates vasorelaxation to anandamide and abnormal‐cannabidiol and is blocked by O‐1918 and by high concentrations of rimonabant. This study investigates VSN16, a novel water‐soluble agonist, as a vasorelaxant potentially acting at non‐CB1, non‐CB2 cannabinoid receptors in the vasculature.Experimental approach:VSN16 and some analogues were synthesized and assayed for vasodilator activity in the rat third generation mesenteric artery using wire myography. Also carried out with VSN16 were haemodynamic studies in conscious rats and binding studies to CB1 receptors of rat cerebellum.Key results:VSN16 relaxed mesenteric arteries in an endothelium‐dependent manner. The vasorelaxation was antagonized by high concentrations of the classical cannabinoid antagonists, rimonabant and AM 251, as well as by O‐1918, an antagonist at the abnormal‐cannabidiol receptor but not at CB1 or CB2 receptors. It did not affect [3H]CP55,940 binding to CB1 receptors in rat cerebellum. The vasorelaxation was not pertussis toxin‐sensitive but was reduced by inhibition of nitric oxide synthesis, Ca2+‐sensitive K+ channels (KCa) and TRPV1 receptors. In conscious rats VSN16 transiently increased blood pressure and caused a longer‐lasting increase in mesenteric vascular conductance. Structure‐activity studies on vasorelaxation showed a stringent interaction with the target receptor.Conclusions and implications:VSN16 is an agonist at a novel cannabinoid receptor of the vasculature. It acts on the endothelium to release nitric oxide and activate KCa and TRPV1. As it is water‐soluble it might be useful in bringing about peripheral cannabinoid‐like effects without accompanying central or severe cardiovascular responses.British Journal of Pharmacology (2007) 152, 751–764; doi:10.1038/sj.bjp.0707470; published online 24 September 2007

  DOI：

  10.1038/sj.bjp.0707470

文献信息

• [EN] COMPOUNDS FOR TREATING DISORDERS ASSOCIATED WITH BK CHANNEL MODULATION<br/>[FR] COMPOSÉS POUR LE TRAITEMENT DE TROUBLES ASSOCIÉS À LA MODULATION DU CANAL BK
  申请人：CANBEX THERAPEUTICS LTD

  公开号：WO2016128771A1

  公开（公告）日：2016-08-18

  The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein: Z is OR16 or NR17R18; R16 is H or alkyl; R17 is H or alkyl; R18 is alkyl or cycloalkyl, each of which is optionally substituted by one or more substituents selected from OH, halogen and COOR11; X is a group selected from -C≡C-

  本发明涉及一种式I的化合物，或其药学上可接受的盐、溶剂或前药，其中：Z为OR16或NR17R18；R16为H或烷基；R17为H或烷基；R18为烷基或环烷基，每个烷基或环烷基可选择地被一个或多个OH、卤素和COOR11取代；X为从-C≡C-<(CH2)P-；-C
• COMPOUNDS FOR TREATING DISORDERS ASSOCIATED WITH BK CHANNEL MODULATION
  申请人：Canbex Therapeutics Limited

  公开号：US20180116983A1

  公开（公告）日：2018-05-03

  The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein: Z is OR 16 or NR 17 R 18 ; R 16 is H or alkyl; R 17 is H or alkyl; R 18 is alkyl or cycloalkyl, each of which is optionally substituted by one or more substituents selected from OH, halogen and COOR 11 ; X is a group selected from —C≡C—
• US9120723B2
  申请人：——

  公开号：US9120723B2

  公开（公告）日：2015-09-01
• Vascular pharmacology of a novel cannabinoid-like compound, 3-(5-dimethylcarbamoyl-pent-1-enyl)-<i>N</i> -(2-hydroxy-1-methyl-ethyl)benzamide (VSN16) in the rat
  作者：P M Hoi、C Visintin、M Okuyama、S M Gardiner、S S Kaup、T Bennett、D Baker、D L Selwood、C R Hiley

  DOI：10.1038/sj.bjp.0707470

  日期：2007.11

  Background and purpose:A putative novel cannabinoid receptor mediates vasorelaxation to anandamide and abnormal‐cannabidiol and is blocked by O‐1918 and by high concentrations of rimonabant. This study investigates VSN16, a novel water‐soluble agonist, as a vasorelaxant potentially acting at non‐CB1, non‐CB2 cannabinoid receptors in the vasculature.Experimental approach:VSN16 and some analogues were synthesized and assayed for vasodilator activity in the rat third generation mesenteric artery using wire myography. Also carried out with VSN16 were haemodynamic studies in conscious rats and binding studies to CB1 receptors of rat cerebellum.Key results:VSN16 relaxed mesenteric arteries in an endothelium‐dependent manner. The vasorelaxation was antagonized by high concentrations of the classical cannabinoid antagonists, rimonabant and AM 251, as well as by O‐1918, an antagonist at the abnormal‐cannabidiol receptor but not at CB1 or CB2 receptors. It did not affect [3H]CP55,940 binding to CB1 receptors in rat cerebellum. The vasorelaxation was not pertussis toxin‐sensitive but was reduced by inhibition of nitric oxide synthesis, Ca2+‐sensitive K+ channels (KCa) and TRPV1 receptors. In conscious rats VSN16 transiently increased blood pressure and caused a longer‐lasting increase in mesenteric vascular conductance. Structure‐activity studies on vasorelaxation showed a stringent interaction with the target receptor.Conclusions and implications:VSN16 is an agonist at a novel cannabinoid receptor of the vasculature. It acts on the endothelium to release nitric oxide and activate KCa and TRPV1. As it is water‐soluble it might be useful in bringing about peripheral cannabinoid‐like effects without accompanying central or severe cardiovascular responses.British Journal of Pharmacology (2007) 152, 751–764; doi:10.1038/sj.bjp.0707470; published online 24 September 2007