H-Har(HCl)-OMe*2HCl | 56217-34-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 精氨酸类衍生物
• 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: H-Har(HCl)-OMe*2HCl
• 英文别名: methyl (2S)-2-amino-6-(diaminomethylideneamino)hexanoate;hydrochloride
• CAS: 56217-34-6
• 化学式: C₈H₁₈N₄O₂*2ClH
• 分子量: 275.178
• InChiKey: YNEZJPGYWITYAV-RGMNGODLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.44
• 重原子数：
  15
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  117
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  H-Har(HCl)-OMe*2HCl 在 溶剂黄146 盐酸 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 为溶剂， 生成 C.<-Tyr(n-Pr)-Har->.CH3COOH
  参考文献：
  名称：

  Studies on analgesic oligopeptides. II. Structure-activity relationship among thirty analogs of a cyclic dipeptide, cyclo(-Tyr-Arg-)

  摘要：

  合成了30种双吡咯并哌嗪类环(-Tyr-Arg-)类似物，并评价了它们对小鼠脑室内给药后的镇痛活性。在环(-X-Arg-)系列类似物中，环[-Tyr(Et)-Arg-]显示出最强的活性。在环(-Tyr-Y-)系列类似物中，活性按Y=高精氨酸、对胍苯丙氨酸、2-氨基-4-胍基丁酸、赖氨酸、鸟氨酸、组氨酸、α,γ-二氨基丁酸和脯氨酸的顺序递减。在合成的类似物中，环-[-Tyr(Et)-Har-]基于上述结果设计，表现出极其强大的镇痛活性，比环(-Tyr-Arg-)强17倍，按摩尔计算几乎与吗啡一样有效。根据这些结果，讨论了环(-Tyr-Arg-)的构效关系。

  DOI：

  10.1248/cpb.30.4435
• 作为产物：
  描述：

  2-methyl-1-(6-(naphthalen-1-yl)pyridin-3-yl)propan-1-one 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 H-Har(HCl)-OMe*2HCl
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Novel Arginine Analogs as Potential Inhibitors of Acetylcholine-Induced Relaxation in Rat Thoracic Aortic Rings

  摘要：

  It is widely appreciated that the vascular endothelium is capable of modulating vascular smooth muscle tone suiting it well for its role as an important regulator of a number of diverse biological processes. Endothelial dysfunction is an early manifestation of atherothrombosis and a consequence of the established disease. Although several arginine derivatives alkylated at one of the guanidino nitrogen were found to inhibit vasorelaxation induced by acetylcholine, activity of the corresponding arginine esters is not reported. The present work was therefore designed to synthesize and evaluate series of novel arginine derivatives to obtain further insight into structure–activity relationship in this series of compounds. Present study involves assessment of activity of these novel compounds on the vascular tone of rat thoracic aorta in comparison with l‐arginine analog, that is, l‐nitro‐arginine methyl ester (l‐NAME). Results from the present study showed that full reversal of phenylephrine‐mediated contraction was achieved by cumulative applications of acetylcholine (3 nm–300 μm), which were abolished when the aortic rings were pretreated with l‐NAME (300 μm). Results from the present study demonstrated that these novel arginine derivatives cause significant yet reversible reduction in acetylcholine‐mediated relaxation, similar to that of l‐NAME.

  DOI：

  10.1111/j.1747-0285.2011.01286.x

文献信息

• Synthesis and Pharmacological Evaluation of Novel Arginine Analogs as Potential Inhibitors of Acetylcholine-Induced Relaxation in Rat Thoracic Aortic Rings
  作者：Manish Jain、Manoj Kumar Barthwal、Wahajul Haq、Seturam B. Katti、Madhu Dikshit

  DOI：10.1111/j.1747-0285.2011.01286.x

  日期：2012.4

  It is widely appreciated that the vascular endothelium is capable of modulating vascular smooth muscle tone suiting it well for its role as an important regulator of a number of diverse biological processes. Endothelial dysfunction is an early manifestation of atherothrombosis and a consequence of the established disease. Although several arginine derivatives alkylated at one of the guanidino nitrogen were found to inhibit vasorelaxation induced by acetylcholine, activity of the corresponding arginine esters is not reported. The present work was therefore designed to synthesize and evaluate series of novel arginine derivatives to obtain further insight into structure–activity relationship in this series of compounds. Present study involves assessment of activity of these novel compounds on the vascular tone of rat thoracic aorta in comparison with l‐arginine analog, that is, l‐nitro‐arginine methyl ester (l‐NAME). Results from the present study showed that full reversal of phenylephrine‐mediated contraction was achieved by cumulative applications of acetylcholine (3 nm–300 μm), which were abolished when the aortic rings were pretreated with l‐NAME (300 μm). Results from the present study demonstrated that these novel arginine derivatives cause significant yet reversible reduction in acetylcholine‐mediated relaxation, similar to that of l‐NAME.
• Studies on analgesic oligopeptides. II. Structure-activity relationship among thirty analogs of a cyclic dipeptide, cyclo(-Tyr-Arg-)
  作者：YUSUKE SASAKI、YASUYUKI AKUTSU、MICHIKO MATSUI、KENJI SUZUKI、SHINOBU SAKURADA、TAKUMI SATO、KENSUKE KISARA

  DOI：10.1248/cpb.30.4435

  日期：——

  Thirty diketopiperazines were synthesized as analogs of cyclo (-Tyr-Arg-). The analgesic activities of these analogs were evaluated after intracerebral administration in mice. In the cyclo (-X-Arg-) series of analogs, cyclo [-Tyr (Et)-Arg-] showed the most potent activity. In the cyclo (-Tyr-Y-) series of analogs, the activity decreased in the order Y=homoarginine, p-guanidinophenylalanine, 2-amino-4-guanidinobutyric acid, Lys, Orn, His, α, γ-diaminobutyric acid and Pro. Among the analogs synthesized, cyclo-[-Tyr (Et)-Har-], which was designed on the basis of the above results, exhibited remarkably potent analgesic activity, being 17 times more potent than cyclo (-Tyr-Arg-) and nearly as potent as morphine on a molar basis. The structure-activity relation of cyclo(-Tyr-Arg-) is discussed in the light of these results.

  合成了30种双吡咯并哌嗪类环(-Tyr-Arg-)类似物，并评价了它们对小鼠脑室内给药后的镇痛活性。在环(-X-Arg-)系列类似物中，环[-Tyr(Et)-Arg-]显示出最强的活性。在环(-Tyr-Y-)系列类似物中，活性按Y=高精氨酸、对胍苯丙氨酸、2-氨基-4-胍基丁酸、赖氨酸、鸟氨酸、组氨酸、α,γ-二氨基丁酸和脯氨酸的顺序递减。在合成的类似物中，环-[-Tyr(Et)-Har-]基于上述结果设计，表现出极其强大的镇痛活性，比环(-Tyr-Arg-)强17倍，按摩尔计算几乎与吗啡一样有效。根据这些结果，讨论了环(-Tyr-Arg-)的构效关系。