(R)-VSN16 | 1246960-09-7

• 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)-VSN16
• 英文别名: (R,Z)-3-(6-(dimethylamino)-6-oxohex-1-en-1-yl)-N-(1-hydroxypropan-2-yl)benzamide；VSN16R；(R)-3-(5-dimethylcarbamoyl-pent-1-enyl)-N-(2-hydroxy-1-methyl-ethyl)benzamide；3-((Z)-6-(Dimethylamino)-6-oxo-hex-1-enyl)-N-((1R)-2-hydroxy-1-methyl-ethyl)benzamide；3-[(Z)-6-(dimethylamino)-6-oxohex-1-enyl]-N-[(2R)-1-hydroxypropan-2-yl]benzamide
• CAS: 1246960-09-7
• 化学式: C₁₈H₂₆N₂O₃
• 分子量: 318.416
• InChiKey: SVYRYFAUQHVGAI-BMWLXYDHSA-N

物化性质

• 沸点：
  547.9±50.0 °C(Predicted)
• 密度：
  1.103±0.06 g/cm3(Predicted)

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-[(1Z)-6-(dimethylamino)-6-oxohex-1-en-1-yl]-N-(2-triisopropylsilyloxy-1-methyl-ethyl)benzamide 在 四丁基氟化铵 、 盐酸 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 18.0h， 以70.3%的产率得到(R)-VSN16
  参考文献：
  名称：

  [EN] PROCESS FOR PREPARING CARBOXYLIC ACID AMIDES USEFUL IN THE TREATMENT OF MUSCULAR DISORDERS
  [FR] PROCÉDÉ

  摘要：

  本发明涉及一种制备化合物的过程，其化学式为其中：R2为环烷基或烷基，每种均可选择性地被取代；Y为-CONR3R4，-CN或CO2R5；R3、R4和R5分别独立地为H或烷基；n为1至6；其中所述过程包括以下步骤：(i) 用具有化学式（IV）的化合物处理化学式（V）的化合物，并形成化学式（IIIb）的化合物；(ii) 用化学式（IIIb）的化合物处理化学式（Il）的化合物，形成化学式（I）的化合物。

  公开号：

  WO2010116116A1

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
• 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
• CRYSTALLINE FORM OF VSN16
  申请人：UCL Business PLC

  公开号：EP2945619B1

  公开（公告）日：2019-05-08
• BENZAMIDE DERIVATIVES USEFUL IN THE TREATMENT OF MUSCULAR DISORDERS AND PAIN AND FOR CONTROLLING SPASTICITY AND TREMORS
  申请人：CANBEX THERAPEUTICS LIMITED

  公开号：US20160304441A1

  公开（公告）日：2016-10-20

  The present invention relates to a compound of formula I, or a pharmaceutically acceptable salt thereof : (I) wherein: n is 0 or 1; R1 is selected from H, alkyl and aralkyl, wherein said alkyl and aralkyl groups may be optionally substituted by one or more OH groups; X is a group selected from —C≡C—(CH 2 ) p —; —C(R 5 )═C(R 6 )—(CH 2 ) q —; and —C(R 5 )(R 6 )C(R 7 )(R 8 )—(CH 2 )r—; where each of R 5 , R 6 , R 7 and is independently II or alkyl, and each of p, q and r is independently 1, 2, 3, 4 or 5; Y is a group selected from: CN; COOR 2 ; CONR 3 R 4 ; SO 2 NR 9 R 10 ; NR 12 COR 13 ; NR 14 SO 2 R 15 ; and a heterocyclic group selected from oxadiazolyl, thiazolyl, isothiazolyl, oxazolyl, iso-oxazolyl, pyrazolyl and imidazolyl; where each of R 2 , R 3 and R 4 is independently H or alkyl; or R 3 and R 4 are linked, together with the nitrogen to which they are attached, to form a 5 or 6-membered heterocycloalkyl or heterocycloalkenyl group, said heterocycloalkyl or heterocycloalkenyl group optionally containing one or more further groups selected from O, N, CO and S, and where each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 and R 15 is independently H or alkyl. Further aspects of the invention relate to the use of such compounds in the preparation of a medicament for the treatment of a muscular disorder, pain, or for controlling spasticity or tremors, for example, spasticity in MS.
• 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—