N-n-pentyl-N'-hydroxyguanidine | 115050-27-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-n-pentyl-N'-hydroxyguanidine
• 英文别名: 1-hydroxy-2-pentylguanidine
• CAS: 115050-27-6
• 化学式: C₆H₁₅N₃O
• 分子量: 145.205
• InChiKey: SPWOUBMFDVMIEZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  10
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  70.6
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  pentyl cyanamide 在 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 N-n-pentyl-N'-hydroxyguanidine
  参考文献：
  名称：

  Novel substrates for nitric oxide synthases

  摘要：

  Enzymatic generation of nitric oxide (NO) by nitric oxide synthase (NOS) consists of two oxidation steps. The first step converts L-arginine to N-G-hydroxy-L-arginine (NOHA), a key intermediate, and the second step converts NOHA to NO and L-citrulline. To fully probe the substrate specificity of the second enzymatic step, an extensive structural screening was carried out using a series of N-alkyl (and N-aryl) substituted-N'-hydrosyguanidines (1-14). Among the eleven N-alkyl-N'-hydroxyguanidines evaluated, N-n-propyl (2). N-iso-propyl (3). N-n-butyl (4). N-s-butyl (5). N-iso-butyl (6), N-pentyl (8) and N-iso-pentyl (9) derivatives were efficiently oxidized by the three isoenzymes of NOS (nNOS, iNOS and eNOS) to generate NO. N-Butyl-N'-hydroxyguanidine (4) was the best substrate for iNOS (K-m = 33 muM) and N-iso-propyl-N'-hydroxyguanidine (3) was the best substrate for nNOS (K-m = 56 muM). When the alkyl substituents were too small (such as ethyl 1) or too large (such as hexyl 10 and cyclohexyl 11) the activity decreased significantly. This suggests that the van der Waals interaction between the alkyl group and the hydrophobic cavity in the NOS active site contributes significantly to the relative reactivity of compounds 3-11. Moreover, five N-aryl-N'-hydroxyguanidines were found to be good substrates for iNOS. but not substrates for eNOS and nNOS. N-phenyl-N'-hydroxy- guanidine was the best substrate among them (K-m = 243 muM). This work demonstrates that N-alkyl substituted hydroxyguanidine compounds are novel NOS substrates which 'short-circuit' the first oxidation step of NOS, and N-aryl substituted hydroxyguanidine compounds are isoform selective NOS substrate. (C) 2002 Published by Elsevier Science Ltd.

  DOI：

  10.1016/s0968-0896(02)00155-4

文献信息

• Benzimidazole Derivatives and Preparation Process and Pharmaceutical Uses Thereof
  申请人：WUHAN LL SCIENCE AND TECHNOLOGY DEVELOPMENT CO., LTD

  公开号：US20170022188A1

  公开（公告）日：2017-01-26

  The invention belongs to the technical field of pharmaceutical chemistry, and particularly pertains to benzimidazole derivatives, and preparation process and pharmaceutical uses thereof. Benzimidazole derivatives include Ligustrazine and NO donor derivatives. The kind of the compounds can rapidly release Ligustrazine or No in vivo, so that they can produce effective synergetic effects with Azilsartan, to enhance the anti-hypertension effect, and reduce adverse effects, and the released Ligustrazine can produce ideal protection to patients' livers and kidneys, thereby filling blanks in the prior art

  这项发明属于药物化学技术领域，特别涉及苯并咪唑衍生物及其制备工艺和药用用途。苯并咪唑衍生物包括川芎素和NO供体衍生物。这些化合物可以在体内快速释放川芎素或NO，从而能够与阿利沙坦产生有效的协同作用，增强抗高血压效果，减少不良反应，释放的川芎素可以对患者的肝脏和肾脏产生理想的保护作用，从而填补了先前技术领域的空白。
• [EN] PYRAZOLE DERIVATIVES AS SGC STIMULATORS<br/>[FR] DÉRIVÉS DE PYRAZOLE UTILISÉS COMME STIMULATEURS DE SGC
  申请人：IRONWOOD PHARMACEUTICALS INC

  公开号：WO2016044447A1

  公开（公告）日：2016-03-24

  There are described imidazole and pyrazole derivatives which are useful as stimulators of sGC, particularly NO-independent, heme-dependent stimulators. These compounds are also useful for treating, preventing or managing various disorders that are herein disclosed.

  描述了咪唑和吡唑衍生物，它们可作为sGC的刺激剂，特别是NO独立、依赖血红素的刺激剂。这些化合物还可用于治疗、预防或管理本文中披露的各种疾病。
• [EN] SGC STIMULATORS<br/>[FR] STIMULATEURS DE LA SGC
  申请人：IRONWOOD PHARMACEUTICALS INC

  公开号：WO2015089182A1

  公开（公告）日：2015-06-18

  The present patent application discloses at least the compounds according to Formula 1 shown below, or pharmaceutically acceptable salts thereof, wherein ringjB,n, JD, J,0, X, X1, J, RC, and W are as defined herein. These compounds are useful as simulators of soluble sGC.

  本专利申请至少揭示了如下所示的符合Formula 1的化合物，或其药用可接受盐，其中ringjB，n，JD，J，0，X，X1，J，RC和W的定义如本文所述。这些化合物可用作可溶性sGC的模拟物。
• Nitrosated and nitrosylated diuretic compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20050059655A1

  公开（公告）日：2005-03-17

  The invention describes novel nitrosated and/or nitrosylated diuretic compounds or pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated and/or nitrosylated diuretic compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel compositions and kits comprising at least one diuretic compound of the invention, that is optionally nitrosated and/or nitrosylated, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; and (l) treating nephropathy.

  该发明描述了新颖的亚硝基化和/或亚硝酰化利尿化合物或其药用盐，以及包含至少一种亚硝基化和/或亚硝酰化利尿化合物的新型组合物，以及可选地至少一种一氧化氮供体和/或至少一种治疗剂。该发明还提供了包含该发明中至少一种利尿化合物的新型组合物和试剂盒，该利尿化合物可选择地亚硝基化和/或亚硝酰化，并且可选地至少一种一氧化氮供体化合物和/或至少一种治疗剂。该发明还提供了用于(a)治疗由于过多水分和/或电解贮留引起的疾病；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗子痫前期；(k)治疗骨质疏松症；和(l)治疗肾病的方法。
• Nitric oxide enhancing diuretic compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20060189603A1

  公开（公告）日：2006-08-24

  The invention describes novel compositions and kits comprising at least one nitric oxide enhancing diuretic compound, or pharmaceutically acceptable salts thereof, and, optionally, at least one nitric oxide enhancing compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating conditions resulting from excessive water and/or electrolyte retention; (b) treating cardiovascular diseases; (c) treating renovascular diseases; (d) treating diabetes; (e) treating diseases resulting from oxidative stress; (f) treating endothelial dysfunctions; (g) treating diseases caused by endothelial dysfunctions; (h) treating cirrhosis; (j) treating pre-eclampsia; (k) treating osteoporosis; (l) treating nephropathy; (m) treating peripheral vascular diseases; (n) treating portal hypertension; (o) treating central nervous system disorders; (p) treating metabolic syndrome; (q) treating sexual dysfunctions; and (r) hyperlipidemia. The nitric oxide enhancing diuretic compounds comprise at least one nitric oxide enhancing group linked to the diuretic compound through one or more sites such as carbon, oxygen and/or nitrogen via a bond or moiety that cannot be hydrolyzed.

  该发明描述了包含至少一种增强一氧化氮利尿化合物或其药用盐的新型组合物和试剂盒，以及可选地，至少一种增强一氧化氮化合物和/或至少一种治疗剂的试剂盒。该发明还提供了以下方法：(a)治疗由过多水分和/或电解贮留引起的症状；(b)治疗心血管疾病；(c)治疗肾血管疾病；(d)治疗糖尿病；(e)治疗由氧化应激引起的疾病；(f)治疗内皮功能障碍；(g)治疗由内皮功能障碍引起的疾病；(h)治疗肝硬化；(j)治疗子痫前期；(k)治疗骨质疏松症；(l)治疗肾病；(m)治疗外周血管疾病；(n)治疗门静脉高压；(o)治疗中枢神经系统疾病；(p)治疗代谢综合征；(q)治疗性功能障碍；以及(r)高脂血症。增强一氧化氮利尿化合物包括至少一种增强一氧化氮基团，通过碳、氧和/或氮等一个或多个位点与利尿化合物连接，连接通过不能水解的键或基团。