京都啡肽 | 70904-56-2

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 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
• 中文名称: 京都啡肽
• 英文名称: kyotorphin
• 英文别名: KTP；Tyr-Arg；L-tyrosyl-L-arginine；(2S)-2-[[(2S)-2-amino-3-(4-hydroxyphenyl)propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid
• CAS: 70904-56-2
• 化学式: C₁₅H₂₃N₅O₄
• 分子量: 337.379
• InChiKey: JXNRXNCCROJZFB-RYUDHWBXSA-N

物化性质

• 密度：
  1.43±0.1 g/cm3(Predicted)
• 溶解度：
  在水中的溶解度为20mg/mL，澄清
• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -4.3
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  177
• 氢给体数：
  6
• 氢受体数：
  6

安全信息

• 储存条件：
  -20°C密封保存于干燥环境中

制备方法与用途

kyotrophin是一种具有镇痛特性的内源性神经活性二肽，同时它还表现出抗炎和抗菌活性。研究发现，脑脊髓液中kyotrophin的水平与阿尔茨海默病患者神经退行性病变的发展呈负相关。

反应信息

• 作为反应物：
  描述：

  京都啡肽 、 hydrocortisone-21-O-β-carbonylpropionic acid p-nitrophenolic ester 在 N-甲基吗啉 、 1-羟基苯并三唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 以51%的产率得到hydrocortison-21-O-succinyl-tyrosyl-arginine
  参考文献：
  名称：

  Synthesis and analgesic effects of kyotorphin—steroid linkers

  摘要：

  Kyotorphin (KTP, H-Tyr-Arg-OH) was covalently bonded with hydrocortisone or estrone to form the corresponding hydrocortisone-21-O-yl-succinyl-Tyr-ArgOH or estrone-3-O-yl-acyl-Tyr-Arg-OH. Their analgesic activities were investigated using the tail flick test. The potency of the two linkers were significantly higher than that of KTP and the mixture of KTP and hydrocortisone or estrone in the CNS and/or the periphery administration. (C) 2001 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(01)00112-x
• 作为产物：
  描述：

  L-精氨酸 、 L-酪氨酸乙酯 在 盐酸 作用下， 反应 4.0h， 生成 京都啡肽
  参考文献：
  名称：

  Single-step synthesis of kyotorphin in frozen solutions by chymotrypsin

  摘要：

  A novel method of Kyotorphin (H-Tyr-Arg-OH) synthesis without protecting and deprotecting procedures is described -alpha-chymotrypsin-catalyzed aminolysis of H-Tyr-OEt by H-Arg-OH in frozen mixtures. In this one-step process yields of the peptide product above 80% have been obtained.

  DOI：

  10.1016/s0957-4166(00)80359-6

文献信息

• Pharmaceutical compositions of drug-oligomer conjugates and methods of treating diseases therewith
  申请人：——

  公开号：US20030069170A1

  公开（公告）日：2003-04-10

  Pharmaceutical compositions that include a drug-oligomer conjugate, a fatty acid component, and a bile salt component are described. The drug is covalently coupled to an oligomeric moiety. The fatty acid component and the bile salt component are present in a weight-to-weight ratio of between 1:5 and 5:1. Methods of treating diseases in a subject in need of such treatment using such pharmaceutical compositions are also provided, as are methods of providing such pharmaceutical compositions.

  描述了包括药物-寡聚物共轭物、脂肪酸成分和胆盐成分的药物组合物。药物以共价键连接到寡聚物基团上。脂肪酸成分和胆盐成分以1:5至5:1的重量比存在。还提供了利用这种药物组合物治疗需要此类治疗的受试者的方法，以及提供这种药物组合物的方法。
• Methods for synthesizing organoboronic compounds and products thereof
  申请人：Walter Armin

  公开号：US20050119226A1

  公开（公告）日：2005-06-02

  Organoboronic acids, for example Cbz-(R)-Phe-(S)-Pro-(R)-Mpg-B(OH) 2 , are made by hydrolysing their diethanolamine adducts under conditions which avoid substantial C—B bond breakage. The product acids are substantially free of degradation product derived from cleavage of the C—B bond thereof. The acids are used to make base addition salts thereof. The salts are formulated into anti-thrombotic pharmaceutical formulations.

  有机硼酸，例如Cbz-(R)-Phe-(S)-Pro-(R)-Mpg-B(OH)2，是通过在避免大量C—B键断裂的条件下水解它们的二乙醇胺加合物制备的。所得的产物酸基本上不含有从C—B键裂解产生的降解产物。这些酸用于制备它们的碱盐。这些盐被配制成抗血栓药物配方。
• Mixtures of drug-oligomer conjugates comprising polyalkylene glycol, uses thereof, and methods of making same
  申请人：——

  公开号：US20030228275A1

  公开（公告）日：2003-12-11

  A non-polydispersed mixture of conjugates in which each conjugate in the mixture comprises a drug coupled to an oligomer that includes a polyalkylene glycol moiety is disclosed. The mixture may exhibit higher in vivo activity than a polydispersed mixture of similar conjugates. The mixture may be more effective at surviving an in vitro model of intestinal digestion than polydispersed mixtures of similar conjugates. The mixture may result in less inter-subject variability than polydispersed mixtures of similar conjugates.

  披露了一种非多分散混合物，其中混合物中的每个共轭物包括与包含聚乙二醇基团的寡聚物偶联的药物。该混合物可能表现出比类似共轭物的多分散混合物更高的体内活性。该混合物可能比类似共轭物的多分散混合物更有效地在体外模拟肠道消化模型中存活。该混合物可能导致比类似共轭物的多分散混合物更少的受试者间变异性。
• ANTIBODY DRUG
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1731168A1

  公开（公告）日：2006-12-13

  The present invention provides an agent for improving the blood stability of an endogenous ligand, which comprises an antibody that has affinity to the mammalian endogenous ligand but substantially does not neutralize the same, and the above-described agent for the prophylaxis and/or treatment for a disease for which an increase in the blood concentration of the endogenous ligand and/or an prolonged blood half-life is prophylactically or therapeutically effective. Provided that the above-described agent is administered alone to a mammal without co-administering the same or substantially the same compound as the endogenous ligand, the blood stability of the endogenous ligand increases and the receptor activity-regulatory action thereof is enhanced.

  本发明提供了一种用于改善内源配体血液稳定性的药剂，包括一种具有亲和力与哺乳动物内源配体结合但实质上不中和其的抗体，以及上述药剂用于预防和/或治疗增加内源配体血液浓度和/或延长血液半衰期对预防或治疗有效的疾病。只要上述药剂单独给哺乳动物使用，而不与内源配体相同或实质相同的化合物联合给药，内源配体的血液稳定性增加，其受体活性调节作用得到增强。
• [EN] INHIBITORS OF NHE-MEDIATED ANTIPORT<br/>[FR] INHIBITEURS D'ANTIPORT À MÉDIATION PAR NHE
  申请人：ARDELYX INC

  公开号：WO2018129557A1

  公开（公告）日：2018-07-12

  The present disclosure is directed to compounds (Ι') and to their use in methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds (Ι') and their use in methods for the treatment of hypertension. The present disclosure is also directed to compounds (Ι') and to their use in methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

  本公开涉及化合物(Ι')及其在治疗与液体潴留或盐超负荷相关的疾病的方法中的用途，例如心力衰竭（尤其是充血性心力衰竭）、慢性肾病、终末期肾病、肝病以及过氧化物酶体增殖物激活受体（PPAR）gamma激动剂引起的液体潴留。本公开还涉及化合物(Ι')及其在治疗高血压的方法中的用途。本公开还涉及化合物(Ι')及其在治疗胃肠道疾病的方法中的用途，包括治疗或减少与胃肠道疾病相关的疼痛。