Ac-Trp-Val-OH | 61389-33-1

• 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: Ac-Trp-Val-OH
• 英文别名: N-Acetyl-L-tryptophyl-L-valine；(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-3-methylbutanoic acid
• CAS: 61389-33-1
• 化学式: C₁₈H₂₃N₃O₄
• 分子量: 345.398
• InChiKey: SCDNQIFYOCLLFF-HOTGVXAUSA-N

物化性质

• 沸点：
  734.4±60.0 °C(Predicted)
• 密度：
  1.258±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	Ac-Trp-Val-OMe	248589-70-0	C19H25N3O4	359.425
  N-乙酰-L-色氨酸	N-AcTrp	1218-34-4	C13H14N2O3	246.266

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(2R,3S)-3-{(S)-2-[(S)-2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino}-2-hydroxy-4-phenyl-butyric acid methyl ester	336611-74-6	C29H36N4O6	536.628
  ——	(2R,3S)-3-{(S)-2-[(S)-2-Acetylamino-3-(1H-indol-3-yl)-propionylamino]-3-methyl-butyrylamino}-2-hydroxy-N-((8S,11S)-8-isopropyl-7,10-dioxo-2-oxa-6,9-diaza-bicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)-4-phenyl-butyramide	——	C45H57N7O8	823.99
  ——	(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-N-[(1S,2R)-1-benzyl-2-hydroxy-3-[[(3S,6S)-6-isopropyl-4,7-dioxo-11,14-dioxa-5,8-diazabicyclo[13.2.2]nonadeca-1(17),15,18-trien-3-yl]amino]-3-oxo-propyl]-3-methyl-butanamide	——	C46H59N7O9	854.016
  ——	(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-N-[(1S,2S,3S)-3-[(2S)-1-[(2S)-2-[[(2S)-2-acetamido-3-(1H-indol-3-yl)propanoyl]amino]-3-methyl-butanoyl]-2-piperidyl]-1-benzyl-2,3-dihydroxy-propyl]-3-methyl-butanamide	1372138-76-5	C51H66N8O8	919.134
  ——	AcNH-Trp-Val-Phe-[Φ]-Pro-Val-Trp-NH-Ac	——	C50H64N8O8	905.107

反应信息

• 作为反应物：
  描述：

  Ac-Trp-Val-OH 在 cis-[Pd(dtcol)(sol)2]²⁺ 、 重水 作用下， 以 丙酮 为溶剂， 生成 L-缬氨酸
  参考文献：
  名称：

  Regioselective Hydrolysis of Tryptophan-Containing Peptides Promoted by Palladium(II) Complexes

  摘要：

  DOI：

  10.1021/ja9840246
• 作为产物：
  描述：

  N-乙酰-L-色氨酸 在 lithium hydroxide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 Ac-Trp-Val-OH
  参考文献：
  名称：

  Design and synthesis of broad-Based mono- and bi- cyclic inhibitors of FIV and HIV proteases

  摘要：

  Based on the substrate transition state and our strategy to tackle the problem of drug resistance, a series of HIV/FIV protease (HIV/FIV PR) monocyclic inhibitors incorporating a 15- or 17-membered macrocycle with an equivalent P3 or P3' group and a unique unnatural amino acid, (2R, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid, have been designed and synthesized. In addition, based on the structure of TL3 with small P3/P3' group, we have synthesized two conformationally restricted bicyclic inhibitors containing the macrocycle, which mimic the P1/P1'-P3/P3' tripeptide [Phe-Val-Ala] of TL3. We have found that the contribution of the macrocycle in our monocyclic inhibitors is important to the overall activity, but the ring size does not affect the activity to a significant extent. Several inhibitors that were developed in this work, exhibit low nanomolar inhibitory activity against the wild-type HIV/FIV PR and found to be highly effective against some drug-resistant as well as TL3-resistant mutants of HIV PRs. Compound 15, in particular, is the most effective cyclic inhibitor in hand to inhibit FIV replication in tissue culture at a concentration of 1.0 mug/mL (1.2 muM). (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00054-3

文献信息

• [EN] PEPTIDOMIMETIC INHIBITORS OF RETROVIRAL PROTEASES AND THEIR USE AS ANTIVIRALS<br/>[FR] INHIBITEURS PEPTIDOMIMETIQUES DE PROTEASES RETROVIRALES ET LEURS UTILISATIONS EN TANT QU'ANTIVIRAUX
  申请人：UNIV DEGLI STUDI TRIESTE

  公开号：WO2005123067A1

  公开（公告）日：2005-12-29

  The patent describes new peptidomimetic inhibitors of retroviral proteases, in particular of human immunodeficiency virus (HIV) protease. These inhibitors comprise as the core structure a new diaminodiol isostere of the dipeptide Phe-Pro having four stereogenic centres. The inhibitors of the invention have been shown to inhibit HIV protease and can therefore be usefully employed as antivirals for post-exposure prophylaxis and as a therapy for viral infections by a retrovirus, in particular HIV. The syntheses processes of the isosteres and inhibitors are also described.

  该专利描述了新的肽类模拟抑制剂，特别是针对人类免疫缺陷病毒（HIV）蛋白酶的抑制剂。这些抑制剂的核心结构是一种新的二氨二醇异构体，与二肽Phe-Pro具有四个立体中心。该发明的抑制剂已被证明能够抑制HIV蛋白酶，因此可以作为抗病毒药物用于事后暴露预防以及治疗由逆转录病毒引起的病毒感染，特别是HIV。该异构体和抑制剂的合成过程也有描述。
• Structure–activity studies of FIV and HIV protease inhibitors containing allophenylnorstatine
  作者：V Le

  DOI：10.1016/s0968-0896(00)00346-1

  日期：2001.5

  potency against the HIV protease in vitro. Within this series, 31 (VLE776) is the most effective inhibitor against FIV protease, and it contains Phe at P3, but no P3' residue. VLE776 also exhibited potent antiviral activities against the drug-resistant HIV mutants (G48V and V82F) and the TL3-resistant HIV mutants. Explanation of the inhibition activities was described. In addition, a new strategy was described

  已使用不对称竞争抑制剂研究了P1和P3侧链与HIV和FIV蛋白酶的结合的S1和S3疏水亚位的相互作用。所评估的抑制剂含有（2S，3S）-3-氨基-2-羟基-4-苯基丁酸（allophenylnorstatine）为羟甲基羰基等排酮，（R）-5,5-二甲基-1，3-噻唑烷-4-羰基为P1'，Val为P2和P2'残基，以及P3和P3'位置的各种氨基酸。在体外，所有抑制剂均显示出对两种酶的竞争性抑制，对HIV蛋白酶的抑制力更高。在这个系列中，31（VLE776）是最有效的FIV蛋白酶抑制剂，它在P3处含有Phe，但没有P3'残基。VLE776还表现出了对耐药HIV突变体（G48V和V82F）和TL3耐药HIV突变体的有效抗病毒活性。描述了抑制活性。另外，描述了开发双功能抑制剂的新策略，该双功能抑制剂将蛋白酶抑制剂和另一种酶抑制剂结合在一个分子中。
• Synthesis and Biological Activity of Potent HIV-1 Protease Inhibitors Based on Phe-Pro Dihydroxyethylene Isosteres
  作者：Fabio Benedetti、Federico Berti、Sara Budal、Pietro Campaner、Francesca Dinon、Alessandro Tossi、Radka Argirova、Petia Genova、Vasil Atanassov、Anton Hinkov

  DOI：10.1021/jm3001136

  日期：2012.4.26

  describe the synthesis and biological activity of HIV-1 PR inhibitors based on four novel dihydroxyethylene isosteres of the Phe-Pro and Pro-Pro dipeptides. The isosteres, containing four stereogenic centers, were synthesized in high yield and excellent stereoselectivity via the cyclization of epoxy amines derived from α-amino acids. The inhibitors were assembled by coupling the isosteres with suitable

  HIV-1 PR的拟肽抑制剂仍然是抗击艾滋病的重要资源。在这里，我们描述了基于Phe-Pro和Pro-Pro二肽的四个新型二羟基乙烯等位基因的HIV-1 PR抑制剂的合成和生物学活性。通过衍生自α-氨基酸的环氧胺的环化反应，以高收率和出色的立体选择性合成了包含四个立体生成中心的等排体。通过将等排体与合适的侧翼基团偶联来组装抑制剂，并针对重组HIV PR进行筛选，以显示在纳摩尔至微摩尔范围内的活性。进一步研究了两种在纳摩尔水平具有活性的基于Phe-Pro的抑制剂：这两种抑制剂结合了抑制HIV-1在感染的MT-2细胞中复制的能力，并且对相同细胞的细胞毒性较低，从而显示出高的治疗指数。这些结果证明了新的Phe-Pro二羟基乙烯等排酮作为强大的HIV-1 PR抑制剂核心单元的潜力。
• Design, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3′ residue
  作者：Chi Ching Mak、Van-Duc Le、Ying-Chuan Lin、John H Elder、Chi-Huey Wong

  DOI：10.1016/s0960-894x(00)00641-7

  日期：2001.1

  A series of norstatine-based HIV/FIV protease inhibitors incorporating a 15-membered macrocycle as a mimic of the tripeptide (Ala-Val-Phe), a motif with a small P3' residue effective against the FIV protease and the drug-resistant HIV proteases, has been synthesized. It was found that the macrocycle is important to the overall activity of the inhibitors. Certain inhibitors were developed expressing low nanomolar inhibitory activity against the HIV/FIV proteases and they are also effective against some drug-resistant as well as TL3-resistant HIV proteases. (C) 2001 Elsevier Science Ltd. All rights reserved.
• Design and synthesis of broad-Based mono- and bi- cyclic inhibitors of FIV and HIV proteases
  作者：Chi Ching Mak、Ashraf Brik、Danica L Lerner、John H Elder、Garrett M Morris、Arthur J Olson、Chi-Huey Wong

  DOI：10.1016/s0968-0896(03)00054-3

  日期：2003.5

  Based on the substrate transition state and our strategy to tackle the problem of drug resistance, a series of HIV/FIV protease (HIV/FIV PR) monocyclic inhibitors incorporating a 15- or 17-membered macrocycle with an equivalent P3 or P3' group and a unique unnatural amino acid, (2R, 3S)-3-amino-2-hydroxy-4-phenylbutyric acid, have been designed and synthesized. In addition, based on the structure of TL3 with small P3/P3' group, we have synthesized two conformationally restricted bicyclic inhibitors containing the macrocycle, which mimic the P1/P1'-P3/P3' tripeptide [Phe-Val-Ala] of TL3. We have found that the contribution of the macrocycle in our monocyclic inhibitors is important to the overall activity, but the ring size does not affect the activity to a significant extent. Several inhibitors that were developed in this work, exhibit low nanomolar inhibitory activity against the wild-type HIV/FIV PR and found to be highly effective against some drug-resistant as well as TL3-resistant mutants of HIV PRs. Compound 15, in particular, is the most effective cyclic inhibitor in hand to inhibit FIV replication in tissue culture at a concentration of 1.0 mug/mL (1.2 muM). (C) 2003 Elsevier Science Ltd. All rights reserved.