H-Phe-Pro-NH2*HCl | 83871-05-0

• 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: H-Phe-Pro-NH2*HCl
• 英文别名: L-Phe-L-Pro-NH2 hydrochloride；phenylalanylproline amide hydrochloride；Phe-Pro-NH2 hydrochloride；(2S)-1-[(2S)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carboxamide;hydrochloride
• CAS: 83871-05-0
• 化学式: C₁₄H₁₉N₃O₂*ClH
• 分子量: 297.785
• InChiKey: MHNJLOIRCMUKNI-FXMYHANSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.45
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  89.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  H-Phe-Pro-NH2*HCl 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 (2S)-N-[(2S)-1-[(2S)-2-氨基甲酰吡咯烷-1-基]-1-氧代-3-苯基丙烷-2-基]-5-氧代吡咯烷-2-甲酰胺
  参考文献：
  名称：

  促甲状腺激素释放激素类似物的合成。1.促甲状腺激素释放活性中枢神经系统作用完全分离。

  摘要：

  合成了在位置2主要包含脂肪族氨基酸的二十四种促甲状腺激素释放激素（TRH）类似物，并测试了其中枢神经系统（CNS）和激素（TSH）的活性。五氟苯基酯方法在合成中的应用导致了最佳收率和高纯度的产物。具有三元或四元直链或支链烷基侧链的中性三肽pGlu-Nva-Pro-NH2（9），pGlu-Nle-Pro-NH2（10）和pGlu-Leu-Pro-NH2（3）中央氨基酸位置的抗癫痫作用比TRH强2.5至10倍，表明组氨酸的存在对于CNS活性不是必需的。与TRH相比，类似物9表现出十倍的抗过敏活性，并且发现其在释放TSH方面完全没有活性。

  DOI：

  10.1021/jm00372a006
• 作为产物：
  描述：

  L-脯氨酰胺 在 盐酸 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 生成 H-Phe-Pro-NH2*HCl
  参考文献：
  名称：

  促甲状腺激素释放激素类似物的合成。1.促甲状腺激素释放活性中枢神经系统作用完全分离。

  摘要：

  合成了在位置2主要包含脂肪族氨基酸的二十四种促甲状腺激素释放激素（TRH）类似物，并测试了其中枢神经系统（CNS）和激素（TSH）的活性。五氟苯基酯方法在合成中的应用导致了最佳收率和高纯度的产物。具有三元或四元直链或支链烷基侧链的中性三肽pGlu-Nva-Pro-NH2（9），pGlu-Nle-Pro-NH2（10）和pGlu-Leu-Pro-NH2（3）中央氨基酸位置的抗癫痫作用比TRH强2.5至10倍，表明组氨酸的存在对于CNS活性不是必需的。与TRH相比，类似物9表现出十倍的抗过敏活性，并且发现其在释放TSH方面完全没有活性。

  DOI：

  10.1021/jm00372a006

文献信息

• Potential Thyroliberin Affinity Labels II: Chloroacetyl Substituted Phenylalanyl Prolineamides
  作者：Richard J. Goebel、Bruce L. Currie、Cyril Y. Bowers

  DOI：10.1002/jps.2600710928

  日期：1982.9

  Three analogs of thyroliberin (I) were prepared. These compounds, N-m-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIa), N-p-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIb) and N-chloroacetyl-alanyl-phenylalanyl-prolineamide (IX), were designed as potential I antagonist affinity labels. However, no significant antagonist activity was observed. Compounds VIa and IX were found to have weak agonist

  制备了三种甲状腺素（I）类似物。这些化合物Nm-氯乙酰基苯甲酰基-苯丙氨酰-脯氨酸（VIa），Np-氯乙酰基苯甲酰基-苯丙氨酰-脯氨酸（VIb）和N-氯乙酰基-苯丙酰基-苯丙氨酰-脯氨酸（IX）被设计为潜在的I拮抗剂亲和标记。但是，没有观察到明显的拮抗剂活性。发现化合物VIa和IX具有弱的激动剂活性。然而，发现环（Phe-Pro）是I代谢产物的类似物，环（His-Pro）具有明显的I拮抗剂活性，但没有激动剂活性。
• Novel thiazine derivatives
  申请人：SANTEN PHARMACEUTICAL CO.,LTD.

  公开号：US20040097496A1

  公开（公告）日：2004-05-20

  A compound having 3-oxo-3,4-dihydro-2H-1,4-thiazine 4-tetrahydropyrazine as a main skeleton. The compound is a chymase inhibitor and is represented by the following formula [I] and salts thereof: 1 In the formula [I], X is S; R 1 and R 2 are H, alkyl, cycloalkyl or aryl; R 3 and R 4 are H, alkyl, cycloalkyl, aryl or an aromatic heterocycle; R 5 is H, alkyl, cycloalkyl, aryl or -A 3 -A 4 -R 7 ; R 6 is H, alkyl, cycloalkyl, hydroxy, alkoxy, aryl, aryloxy or an aromatic heterocycle; R 7 is H, alkyl, hydroxy, alkoxy, aryl, aryloxy, amino, alkylamino, arylamino, an aromatic heterocycle or a nonaromatic heterocycle; A 1 is alkylene; A 2 is carbonyl or sulfonyl; A 3 is alkylene; A 4 is carbonyl or oxalyl; and n is 0 or 1.

  化合物具有3-氧代-3,4-二氢-2H-1,4-噻嗪-4-四氢吡嗪作为主要骨架。该化合物是一种Chymase抑制剂，由以下公式[I]及其盐所表示：1在公式[I]中，X为S；R1和R2为H，烷基，环烷基或芳基；R3和R4为H，烷基，环烷基，芳基或芳香族杂环；R5为H，烷基，环烷基，芳基或-A3-A4-R7；R6为H，烷基，环烷基，羟基，烷氧基，芳基，芳氧基或芳香族杂环；R7为H，烷基，羟基，烷氧基，芳基，芳氧基，氨基，烷基氨基，芳基氨基，芳香族杂环或非芳香族杂环；A1为烷基；A2为羰基或磺酰基；A3为烷基；A4为羰基或草酰基；n为0或1。
• NOVEL THIAZINE OR PYRAZINE DERIVATIVES
  申请人：SANTEN PHARMACEUTICAL CO., LTD.

  公开号：EP1211249A1

  公开（公告）日：2002-06-05

  An object of the present invention is to synthesize novel compounds having 3-oxo-3, 4-dihydro-2H-1, 4-thiazine or 2-oxo-1, 2, 3, 4-tetrahydropyrazine as a main skeleton. The present invention relates to compounds represented by the following general formula [I] and salts thereof. In the formula, X is S or R6-(A2)n-N, R1 and R2 are H, alkyl, cycloalkyl or aryl, R3 and R4 are H, alkyl, cycloalkyl, aryl or aromatic heterocycles, R5 is H, alkyl, cycloalkyl, aryl or -A3-A4-R7, R6 is H, alkyl, cycloalkyl, OH, alkoxy, aryl, aryloxy or an aromatic heterocycle, R7 is H, alkyl, OH, alkoxy, aryl, aryloxy, amino, alkylamino, arylamino, an aromatic heterocycle or a nonaromatic heterocycle, A1 is alkylene, A2 is carbonyl or sulfonyl, A3 is alkylene, and A4 is carbonyl or oxalyl.

  本发明的目的是合成以3-氧代-3，4-二氢-2H-1，4-噻嗪或2-氧代-1，2，3，4-四氢吡嗪为主要骨架的新型化合物。本发明涉及由以下通式[I]代表的化合物及其盐类。式中，X 是 S 或 R6-(A2)n-N，R1 和 R2 是 H、烷基、环烷基或芳基，R3 和 R4 是 H、烷基、环烷基、芳基或芳香杂环，R5 是 H、烷基、环烷基、芳基或 -A3-A4-R7，R6 是 H、烷基、环烷基、OH、烷氧基、芳基、R7是H、烷基、OH、烷氧基、芳基、芳氧基、氨基、烷基氨基、芳基氨基、芳香杂环或非芳香杂环，A1是亚烷基，A2是羰基或磺酰基，A3是亚烷基，A4是羰基或草酰基。
• Inactivation of trypsin-like proteases by depsipeptides of p-guanidinobenzoic acid
  作者：Vishwas S. Ganu、Elliott Shaw

  DOI：10.1021/jm00138a011

  日期：1981.6

  A number of esters of p-guanidinobenzoic acid have been synthesized which contain a glycolyl peptide as the departing group. In the case of several enzymes such as trypsin and plasma kallikrein, depsipeptides were obtained which were considerably more reactive than the ethyl ester in inactivation of the protease by acyl-enzyme formation; the depsipeptide processing -CH2CO-Phe-NH2 as a leaving group displayed the highest reactivity. They were less effective in the case of urokinase, plasmin, and urinary kallikrein. Boar acrosin was very susceptible to inactivation by both ethyl and peptidyl esters. Depsipeptides possessing a longer peptide chain and a secondary carbon as a leaving group showed lower activities. The results demonstrate the productive use of the departing group region of protease active centers to obtain selectivity.
• Synthesis of Morphiceptin (Tyr-Pro-Phe-Pro-NH₂) by Dipeptidyl Aminopeptidase IV Derived from <i>Aspergillus oryzae</i>
  作者：Toru Ota、Aki Itoh、Hiroshi Tachi、Keita Kudoh、Tatsuo Watanabe、Yuji Yamamoto、Tadahiro Tadokoro、Akio Maekawa

  DOI：10.1021/jf050420d

  日期：2005.7.1

  Morphiceptin (TYr-Pro-Phe-Pro-NH2), tetrapeptide, was synthesized using dipeptidyl aminopeptidase IV (DP IV, EC 3.4.14.5) derived from Aspergillus oryzae RIB 915 as a catalyst. Tyr-Pro-OEt was incubated with Phe-Pro-NH2 in the presence of DID IV under various. conditions of temperature, concentrations of ethylene glycol, pH, reaction time, and others. Morphiceptin was obtained at 40% yield under the optimal reaction conditions: substrate, 4 mM Tyr-Pro-OEt center dot HCl and 20 mM Phe-ProNH(2)center dot HCl; enzyme, DP IV, 0.275 nkat; solvent, 60% ethylene glycol containing 20 mM phosphate buffer at pH 7.0; amine, 4.2 mM diisopropylamine at 4 degrees C for 24 h. Amino group protection was unnecessary for synthesis of morphiceptin by DID IV.