2-(3-Amino-propoxy)-N-[4-(3-guanidino-propoxy)-benzyl]-N-[6-(4-hydroxy-phenoxy)-benzothiazol-2-yl]-benzamide

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(3-Amino-propoxy)-N-[4-(3-guanidino-propoxy)-benzyl]-N-[6-(4-hydroxy-phenoxy)-benzothiazol-2-yl]-benzamide
• 英文别名: 2-(3-aminopropoxy)-N-(4-(3-(diaminomethyleneamino)propoxy)benzyl)-N-(6-(4-hydroxyphenoxy)benzo[d]thiazol-2-yl)benzamide；2-(3-aminopropoxy)-N-[[4-[3-(diaminomethylideneamino)propoxy]phenyl]methyl]-N-[6-(4-hydroxyphenoxy)-1,3-benzothiazol-2-yl]benzamide
• 化学式: C₃₄H₃₆N₆O₅S
• 分子量: 640.763
• InChiKey: BLHUKYKUAQAMCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  46
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  200
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  N-(3-(2-(N-(6-(4-benzyloxyphenoxy)benzothiazol-2-yl)-N-(4-(3-(1,3-dihydro-1,3-dioxoisoindol-2-yl)propoxy)benzyl)carbamoyl)phenoxy)propyl)carbamic acid tert-butyl ester 在 茴香硫醚 、 一水合肼 、 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 105.0h， 生成 2-(3-Amino-propoxy)-N-[4-(3-guanidino-propoxy)-benzyl]-N-[6-(4-hydroxy-phenoxy)-benzothiazol-2-yl]-benzamide
  参考文献：
  名称：

  Synthesis and biological evaluation of nonpeptide mimetics of ω-conotoxin GVIA

  摘要：

  A benzothiazole-derived compound (4a) designed to mimic the C-alpha-C-beta bond vectors and terminal functionalities of Lys2, TyrI3 and Arg17 in omega-conotoxin GVIA was synthesised, together with analogues (4b-d), which had each side-chain mimic systematically truncated or eliminated. The affinity of these compounds for rat brain N-type and P/Q-type voltage gated calcium channels (VGCCs) was determined. In terms of N-type channel affinity and selectivity, two of these compounds (4a and 4d) were found to be highly promising, first generation mimetics of omega-conotoxin. The fully functionalised mimetic (4a) showed low PM binding affinity to N-type VGCCs (IC50 = 1.9 muM) and greater than 20-fold selectivity for this channel sub-type over P/Q-type VGCCs, whereas the mimetic in which the guanidine-type side chain was truncated back to an amine (4d, IC50 = 4.1 muM) showed a greater than 25-fold selectivity for the N-type channel. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.05.040

文献信息

• Synthesis and biological evaluation of nonpeptide mimetics of ω-conotoxin GVIA
  作者：Jonathan B Baell、Peter J Duggan、Stewart A Forsyth、Richard J Lewis、Y Phei Lok、Christina I Schroeder

  DOI：10.1016/j.bmc.2004.05.040

  日期：2004.8.1

  A benzothiazole-derived compound (4a) designed to mimic the C-alpha-C-beta bond vectors and terminal functionalities of Lys2, TyrI3 and Arg17 in omega-conotoxin GVIA was synthesised, together with analogues (4b-d), which had each side-chain mimic systematically truncated or eliminated. The affinity of these compounds for rat brain N-type and P/Q-type voltage gated calcium channels (VGCCs) was determined. In terms of N-type channel affinity and selectivity, two of these compounds (4a and 4d) were found to be highly promising, first generation mimetics of omega-conotoxin. The fully functionalised mimetic (4a) showed low PM binding affinity to N-type VGCCs (IC50 = 1.9 muM) and greater than 20-fold selectivity for this channel sub-type over P/Q-type VGCCs, whereas the mimetic in which the guanidine-type side chain was truncated back to an amine (4d, IC50 = 4.1 muM) showed a greater than 25-fold selectivity for the N-type channel. (C) 2004 Elsevier Ltd. All rights reserved.