N-tert-butyloxycarbonyl-L-phenylalanyl-L-proline amide | 69470-09-3

• 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: N-tert-butyloxycarbonyl-L-phenylalanyl-L-proline amide
• 英文别名: (2S)-1-{(2S)-2-(Aminocarbonyl)pyrrolidin-1-yl}-2-(tert-butoxycarbonyl)amino-3-phenyl-1-propanone；Boc-Phe-Pro-NH2；Boc-L-Phe-L-Pro-NH2；tert-butyl N-[(2S)-1-[(2S)-2-carbamoylpyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]carbamate
• CAS: 69470-09-3；109740-31-0
• 化学式: C₁₉H₂₇N₃O₄
• 分子量: 361.441
• InChiKey: CAOGSKOCNQRIOG-GJZGRUSLSA-N

物化性质

• 熔点：
  76-77 °C
• 沸点：
  621.2±55.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-tert-butyloxycarbonyl-L-phenylalanyl-L-proline amide 在 盐酸 、 三乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 生成 N-(benzyloxycarbonyl)-L-γ-methylglutamyl-L-phenylalanyl-L-prolinamide
  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：

  N-[(1,1-二甲基乙氧基)羰基]-L-苯丙氨酰-L-脯氨酸 在 1-hydroxy-1H-benzotriazole ammonium salt 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-tert-butyloxycarbonyl-L-phenylalanyl-L-proline amide
  参考文献：
  名称：

  Synthesis and biological activity of branched enkephalin analogues

  摘要：

  The synthesis and biological activity of a new type of enkephalin analogs are reported. A series of branched penta peptides of the enkephalin sequence with replacement of 2-glycine by D-ornithine and branching of the peptide chain in position 2 by attachment of proline, leucine, asparagine or methionine residues to the delta-amino group of D-ornithine were synthesized by classical solution methodology. Analgesic activity of the new analogs was assayed by the 'tail pinch' method following intracisternal and intravenous administrations to mice. They showed higher analgesic potency and longer duration of action as compared to linear and cyclic pentapeptides with the same amino acid composition. The activity determined in the GPI and MVD bioassays, and in a binding assay, revealed the preference of the branched analogs for the mu-type of opioid receptor over the delta-type. These results raise the possibility to synthesize enkephalin analogs with high analgesic potency and opiate receptor selectivity by varying the chemical character and length of the side chain in the 2-position. (C) Elsevier, Paris.

  DOI：

  10.1016/s0223-5234(98)80060-3

文献信息

• Development of a practical solid-phase synthesis approach to 1,3,5-triazepan-2,6-diones
  作者：Joel Boeglin、Claire Venin、Gilles Guichard

  DOI：10.1016/j.tet.2012.06.051

  日期：2012.9

  1,3,5-Triazepan-2,6-diones are a class of conformationally restricted heterocycles derived from dipeptides. With the aim to develop a general and practical method useful for library production, three polymer-assisted syntheses, all based on a catch and release approach, have been evaluated and compared. The method involving a Hofmann rearrangement of N-Boc dipeptide carboxamides and subsequent trapping

  1,3,5-Triazepan-2,6-diones是衍生自二肽的一类受构象限制的杂环。为了开发一种适用于文库生产的通用实用方法，已对三种均基于捕获和释放方法的聚合物辅助合成方法进行了评估和比较。发现该方法涉及N- Boc二肽羧酰胺的霍夫曼重排以及随后将异氰酸酯截留在聚合物负载的N-羟基琥珀酰亚胺（PS-HOSu）上，是最可靠，用途最广泛的方法，可快速进入1,3,5 -triazepan-2,6-dione骨架。
• Tripeptides and tripeptide derivatives for the treatment of postlesional diseases of the nervous system
  申请人：Rapin Jean

  公开号：US20050080016A1

  公开（公告）日：2005-04-14

  The invention relates to the use of specific tripeptides for the treatment of postlesional diseases of ischemic, traumatic or toxic origin. The tripeptide derivatives satisfy the following formula (I): (see formula I as in paper form) wherein X represents OH, (C 1-5 ) alkoxy, NH 2 , NH—C 1-5 -alkyl, N(C 1-5 alkyl) 2 ; R 1 is a residue derived from one of the amino acids Phe, Tyr, Trp, Pro, which each may be optionally substituted with one or more (C 1-5 ) alkoxy groups, (C 1-5 ) alkyl groups or halogen atoms, as well as Ala, Val, Leu or Ile; R 2 is a residue derived from one of the amino acids Gly, Ala, Ile, Val, Ser, Thr, and Pro; Y 1 and Y 2 independently from each other represent H or (C 1-5 ) alkyl; R 3 and R 4 independently from each other represent H, OH, (C 1-5 ) alkyl or (C 1-5 ) alkoxy, provided that R 3 and R 4 are not both OH or (C 1-5 ) alkoxy; and R 5 represents H, OH, (C 1-5 ) alkyl or (C 1-5 ) alkoxy; or a pharmaceutically acceptable salt thereof.

  本发明涉及使用特定三肽治疗缺血性、创伤性或毒性后损伤性疾病。该三肽衍生物满足以下式子（I）：（见论文中的式子I） 其中，X代表OH、（C1-5）烷氧基、NH2、NH-C1-5-烷基、N（C1-5烷基）2；R1是来自苯丙氨酸、酪氨酸、色氨酸、脯氨酸中的一种氨基酸残基，每个氨基酸残基都可以选择性地用一个或多个（C1-5）烷氧基、（C1-5）烷基或卤原子取代，以及丙氨酸、缬氨酸、亮氨酸或异亮氨酸；R2是来自甘氨酸、丙氨酸、异亮氨酸、缬氨酸、丝氨酸、苏氨酸和脯氨酸中的一种氨基酸残基；Y1和Y2分别表示H或（C1-5）烷基；R3和R4分别表示H、OH、（C1-5）烷基或（C1-5）烷氧基，前提是R3和R4不同时为OH或（C1-5）烷氧基；R5表示H、OH、（C1-5）烷基或（C1-5）烷氧基；或其药学上可接受的盐。
• Tripeptides and tripeptide derivatives for the treatment of neurodegenerative diseases
  申请人：Rapin Jean

  公开号：US20050101538A1

  公开（公告）日：2005-05-12

  The invention relates to the use of specific tripeptides for the treatment of neurodegenerative diseases, and to pharmaceutical compositions comprising the tripeptides. The tripeptide derivatives satisfy the following formula (I): wherein X represents OH, (C 1-5 ) alkoxy, NH 2 , NH—C 1-5 -alkyl, N(C 1-5 alkyl) 2 ; R 1 is a residue derived from one of the amino acids Phe, Tyr, Trp, Pro, which each may be optionally substituted with one or more (C 1-5 )alkoxy groups, (C 1-5 )alkyl groups or halogen atoms, as well as Ala, Val, Leu or Ile; R 2 is a residue derived from one of the amino acids Gly, Ala, Ile, Val, Ser, Thr, Leu and Pro; Y 1 and Y 2 independently from each other represent H or (C 1-5 )alkyl; R 3 and R 4 independently from each other represent H, OH, (C 1-5 )alkyl or (C 1-5 )alkoxy, provided that R 3 and R 4 are not both OH or (C 1-5 )alkoxy; and R 5 represents H, OH, (C 1-5 )alkyl or (C 1-5 )alkoxy; or a pharmaceutically acceptable salt thereof.

  本发明涉及使用特定三肽治疗神经退行性疾病，以及包含该三肽的药物组合物。该三肽衍生物满足以下公式（I）：其中X代表OH，（C1-5）烷氧基，NH2，NH-（C1-5）烷基，N（C1-5烷基）2；R1是从苯丙氨酸，酪氨酸，色氨酸，脯氨酸中的一个衍生的残基，每个残基可选择地用一个或多个（C1-5）烷氧基，（C1-5）烷基或卤素原子取代，以及丙氨酸，缬氨酸，亮氨酸或异亮氨酸；R2是从甘氨酸，丙氨酸，异亮氨酸，缬氨酸，丝氨酸，苏氨酸，亮氨酸和脯氨酸中的一个衍生的残基；Y1和Y2各自独立地表示H或（C1-5）烷基；R3和R4各自独立地表示H，OH，（C1-5）烷基或（C1-5）烷氧基，前提是R3和R4不是OH或（C1-5）烷氧基；R5表示H，OH，（C1-5）烷基或（C1-5）烷氧基；或其药学上可接受的盐。
• 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。
• Derivatives of L-proline, their preparation and their biological uses
  申请人：Inorgan SA Recherche & Developpement Pharmaceutiques, CAS

  公开号：US05212158A1

  公开（公告）日：1993-05-18

  The L-proline derivatives of the invention correspond to the Formula I: ##STR1## in which R.sub.1 corresponds to the Formula II: ##STR2## in which R is a carbonyl group, an acyl group --Y--CO-- or an oxy-acyl group --O--Y--CO--, Y being an alkyl or an alkenyl chain, Z being one or more hydrogen atoms, or one or more substituents chosen from among halogen atoms, CF.sub.3, alkyl or alkoxy groups and an alkylenedioxy group in the case of two neighbouring substituents, R.sub.2 is --NH.sub.2, --OH, or a derivative of these groups, A.sub.1 and A.sub.2 are amino acid residues and B.sub.1 and B.sub.2 represents a hydrogen atom or a methyl group, and the pharmacologically acceptable salts of these derivatives. These derivatives are useful particularly as the active principles of medicines possessing, in particular, a nootropic action.

  本发明的L-脯氨酸衍生物对应于公式I：##STR1## 其中R.sub.1对应于公式II：##STR2## 其中R是一个羰基基团，一个酰基--Y--CO--或一个氧酰基--O--Y--CO--，其中Y是一个烷基或烯基链，Z是一个或多个氢原子，或一个或多个从卤素原子，CF.sub.3，烷基或烷氧基和两个相邻取代基的烷二氧基基团中选择的取代基，R.sub.2是--NH.sub.2，--OH或这些基团的衍生物，A.sub.1和A.sub.2是氨基酸残基，B.sub.1和B.sub.2代表氢原子或甲基基团，以及这些衍生物的药学上可接受的盐。这些衍生物特别有用作具有神经保护作用的药物的活性成分。