ω-Nitroarginin | 137433-32-0

• 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: ω-Nitroarginin
• 英文别名: Nω-nitro-L-arginine；L-NNA；N^ω-nitro-arginine；N^ω-Nitro-arginin；2-amino-5-[[(Z)-N'-nitrocarbamimidoyl]amino]pentanoic acid
• CAS: 137433-32-0
• 化学式: C₆H₁₃N₅O₄
• mdl: MFCD00273094
• 分子量: 219.2
• InChiKey: MRAUNPAHJZDYCK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  15
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.666
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ω-Nitroarginin 在 盐酸 、 碳酸氢钠 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 N^α,N^im-diTos-N^G-nitro-L-Arg-Gly-Gly-Gly-OMe
  参考文献：
  名称：

  El-Naggar, A. M.; Zaher, M. R.; El-Ghaffar, S. A., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1983, vol. 22, # 4, p. 392 - 395

  摘要：

  DOI：
• 作为产物：
  描述：

  L-nitroarginine methyl ester 以 水 为溶剂， 反应 72.0h， 生成 ω-Nitroarginin
  参考文献：
  名称：

  Inhibition of nitric oxide synthesis by NG-nitro-L-arginine methyl ester (L-NAME): requirement for bioactivation to the free acid, NG-nitro-L-arginine

  摘要：

  The L‐arginine derivatives NG‐nitro‐L‐arginine (L‐NOARG) and NG‐nitro‐L‐arginine methyl ester (L‐NAME) have been widely used to inhibit constitutive NO synthase (NOS) in different biological systems. This work was carried out to investigate whether L‐NAME is a direct inhibitor of NOS or requires preceding hydrolytic bioactivation to L‐NOARG for inhibition of the enzyme. A bolus of L‐NAME and L‐NOARG (0.25 μmol) increased coronary perfusion pressure of rat isolated hearts to the same extent (21 ± 0.8 mmHg; n = 5), but the effect developed more rapidly following addition of L‐NOARG than L‐NAME (mean half‐time: 0.7 vs. 4.2 min). The time‐dependent onset of the inhibitory effect of L‐NAME was paralleled by the appearance of L‐NOARG in the coronary effluent. Freshly dissolved L‐NAME was a 50 fold less potent inhibitor of purified brain NOS (mean IC50 = 70 μm) than L‐NOARG (IC50 = 1.4 μm), but the apparent inhibitory potency of L‐NAME approached that of L‐NOARG upon prolonged incubation at neutral or alkaline pH. H.p.l.c. analyses revealed that NOS inhibition by L‐NAME closely correlated with hydrolysis of the drug to L‐NOARG. Freshly dissolved L‐NAME contained 2% of L‐NOARG and was hydrolyzed with a half‐life of 365 ± 11.2 min in buffer (pH 7.4), 207 ± 1.7 min in human plasma, and 29 ± 2.2 min in whole blood (n = 3 in each case). When L‐NAME was preincubated in plasma or buffer, inhibition of NOS was proportional to formation of L‐NOARG, but in blood the inhibition was much less than expected from the rates of L‐NAME hydrolysis. This was explained by accumulation of L‐NOARG in blood cells. These results suggest that L‐NAME represents a prodrug lacking NOS inhibitory activity unless it is hydrolyzed to L‐NOARG. Bioactivation of L‐NAME proceeds at moderate rates in physiological buffers, but is markedly accelerated in tissues such as blood or vascular endothelium.

  DOI：

  10.1111/j.1476-5381.1996.tb15557.x

文献信息

• [EN] INHIBITORS OF GROWTH FACTOR ACTIVATION ENZYMES<br/>[FR] INHIBITEURS D'ENZYMES D'ACTIVATION DE FACTEUR DE CROISSANCE
  申请人：UNIV WASHINGTON

  公开号：WO2016144654A1

  公开（公告）日：2016-09-15

  The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.

  本发明通常涉及对抑制肝细胞生长因子激活剂、麦曲丝蛋白、赫普星、Xa因子或凝血酶等的化合物有用的化合物。本发明还涉及使用抑制剂化合物的各种方法，包括通过向需要的受试者施用有效量的抑制剂来治疗恶性肿瘤、癌前病变或癌症。
• 1,3-Diarylprop-2-en-1-ones, compositions containing them and use thereof
  申请人：AVENTIS PHARMA S.A.

  公开号：US20030153611A1

  公开（公告）日：2003-08-14

  1,3-Diarylprop-2-en-1-ones and derivatives, compositions containing them, manufacturing process and use. Substituted 1,3-diarylprop-2-en-1-ones with therapeutic activity may be used in oncology.

  1,3-二芳基丙烯酮及其衍生物，含有它们的组合物，制备工艺和用途。具有治疗活性的取代1,3-二芳基丙烯酮可用于肿瘤学。
• 1,3-DIARYLPROP-2-EN-1-ONES, COMPOSITIONS CONTAINING THEM AND USE THEREOF
  申请人：Aventis Pharma S.A.

  公开号：US20040147584A2

  公开（公告）日：2004-07-29

  Abstract of the Disclosure 1,3-Diarylprop-2-en-1-ones and derivatives, compositions containing them, manufacturing process and use. Substituted 1,3-diarylprop-2-en-1-ones with therapeutic activity may be used in oncology.

  本文摘要介绍了1,3-二芳基丙烯酮及其衍生物，包括含有它们的组合物、制备方法和用途。具有治疗活性的取代的1,3-二芳基丙烯酮可用于肿瘤学。
• Polar Hydrophilic Prodrugs of Amphetamine and Other Stimulants and Processes for Making and Using the Same
  申请人：Mickle Travis C.

  公开号：US20080207757A1

  公开（公告）日：2008-08-28

  Disclosed are polar, hydrophilic stimulant prodrug compositions comprising at least one stimulant chemically attached to a polar hydrophilic ligand, a salt thereof, a derivative thereof, or a combination thereof. Methods of making and using the same are also disclosed.

  本发明涉及一种极性、亲水的兴奋剂前药组合物，其包括至少一种兴奋剂与一个极性亲水配体化学结合，其盐、衍生物或其组合物。本发明还公开了制备和使用该组合物的方法。
• SALTS OF TRIMEBUTINE AND N-DESMETHYL TRIMEBUTINE
  申请人：WALLACE L. JOHN

  公开号：US20070275905A1

  公开（公告）日：2007-11-29

  Unique salts of trimebutine and N-monodesmethyl trimebutine, and their corresponding stereoisomers, having improved analgesic properties useful in the treatment of visceral pain are provided. The salts of the present invention are particularly useful in the treatment of conditions characterized by abdominal pain, such as inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), diabetic gastroparesis, and dyspepsia.

  本发明提供了三甲叉胺和N-单去甲基三甲叉胺的独特盐及其对应的立体异构体，具有改善的镇痛特性，可用于治疗内脏疼痛。本发明的盐尤其适用于治疗腹部疼痛症状，例如炎症性肠病（IBD）和肠易激综合征（IBS）、糖尿病性胃轻瘫和消化不良等。