<(benzyloxycarbonyl)-L-valinyl>hydrazinecarboxylic acid tert-butyl ester | 68199-62-2

• 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: <(benzyloxycarbonyl)-L-valinyl>hydrazinecarboxylic acid tert-butyl ester
• 英文别名: tert-butyl N-[[(2S)-2-(benzyloxycarbonylamino)-3-methylbutanoyl]amino]carbamate；Z-Val-NH-NH-Boc；benzyl N-[(2S)-3-methyl-1-[2-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinyl]-1-oxobutan-2-yl]carbamate
• CAS: 68199-62-2；95422-60-9；5564-00-1
• 化学式: C₁₈H₂₇N₃O₅
• 分子量: 365.429
• InChiKey: LNGXCBHJYHXXLY-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  106
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <(benzyloxycarbonyl)-L-valinyl>hydrazinecarboxylic acid tert-butyl ester 在 palladium on activated charcoal N-甲基吗啉 、 盐酸 、 甲酸 、 1-ethyl-3-(3-diaminopropyl)carbodiimide hydrochloride 、 氢气 、 sodium cyanoborohydride 、 对甲苯磺酸 、 1-羟基苯并三唑一水物 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 为溶剂， 5.0~80.0 ℃ 、101.33 kPa 条件下， 反应 90.0h， 生成 (2S)-N-[(2S,3S)-4-[[[(2S)-2-amino-3-methylbutanoyl]amino]-(2-methylpropyl)amino]-3-hydroxy-1-phenylbutan-2-yl]-2-(quinoline-2-carbonylamino)butanediamide
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p
• 作为产物：
  描述：

  L-缬氨酸 在 N-甲基吗啉 、 sodium hydroxide 、 1-ethyl-3-(3-diaminopropyl)carbodiimide hydrochloride 、 1-羟基苯并三唑一水物 作用下， 以 1,4-二氧六环 为溶剂， 反应 34.17h， 生成 <(benzyloxycarbonyl)-L-valinyl>hydrazinecarboxylic acid tert-butyl ester
  参考文献：
  名称：

  Aza-Peptide Analogs as Potent Human Immunodeficiency Virus Type-1 Protease Inhibitors with Oral Bioavailability

  摘要：

  A series of aza-peptide analogs with a (hydroxyethyl)hydrazine isostere has been synthesized as HIV-1 protease inhibitors using a simple synthetic scheme. Structure-activity studies based on the X-ray of a previously described inhibitor-enzyme complex led to potent inhibitors with antiviral activity in the low-nanomolar range. The S-configuration of the transition-state hydroxyl group was preferred in this series. Small modifications of the P2P3 and P-2'P-3' substituents had little effect on enzyme inhibition but greatly influenced the pharmacokinetic profile. As a result of these studies, the symmetrically acylated compound 8a and its close analog 24a bearing a methyl carbamate in P-3 and an ethyl carbamate in P-3' position were identified as potent inhibitors with plasma concentrations exceeding antiviral ED(50) values 150-fold following oral application in mice.

  DOI：

  10.1021/jm960022p

文献信息

• Acyl hydrazines as precursors to acyl radicals
  作者：Rebecca Braslau、Marc O Anderson、Frank Rivera、Armando Jimenez、Terra Haddad、Jonathan R Axon

  DOI：10.1016/s0040-4020(02)00490-8

  日期：2002.7

  The use of acyl hydrazines (hydrazides) as precursors for the stoichiometric generation of acyl radicals is explored. Two classes of substrates are examined: unsubstituted acyl hydrazines and acyl hydrazines substituted with a leaving group (2-nitrobenzenesulfonyl or ‘nosyl’). Both types are successfully converted to acyl radicals, and are then trapped by nitroxide radicals to give acyloxyamine products

  探索了使用酰基肼（酰肼）作为化学计量产生酰基自由基的前体。检查了两类底物：未取代的酰基肼和被离去基团（2-硝基苯磺酰基或“ nosyl”）取代的酰基肼。两种类型均成功转化为酰基自由基，然后被氮氧自由基捕获，得到了酰氧基胺产物。对两种类型的底物都证明了环化反应。还开发了McFayden-Stevens反应的低温修饰方法。
• Carbonylhydrazide-Based Molecular Tongs Inhibit Wild-Type and Mutated HIV-1 Protease Dimerization
  作者：Laure Dufau、Ana Sofia Marques Ressurreição、Roberto Fanelli、Nadjib Kihal、Anamaria Vidu、Thierry Milcent、Jean-Louis Soulier、Jordi Rodrigo、Audrey Desvergne、Karine Leblanc、Guillaume Bernadat、Benoit Crousse、Michèle Reboud-Ravaux、Sandrine Ongeri

  DOI：10.1021/jm300181j

  日期：2012.8.9

  Kinetic analyses and fluorescent probe binding studies showed that several molecular tongs can inhibit PR dimerization. The best nonpeptidic molecular tongs to date were obtained with an inhibition constant Kid of 50 nM for PR and 80 nM for the multimutated protease ANAM-11. The PR inhibition was selective, the aspartic proteases renin and pepsin were not inhibited.

  我们设计和合成了一种基于刚性萘基支架的新型分子钳，并评估了它们对HIV-1蛋白酶（PR）的抗二聚体活性。我们将羰基酰肼和寡酰肼（叠氮化物）片段插入它们的拟肽臂中，以减少疏水性并增加代谢稳定性。这些片段旨在通过复制天然PR中两个单体的N和C端之间形成的反平行β折叠中的氢键模式来破坏蛋白质之间的相互作用。动力学分析和荧光探针结合研究表明，几种分子钳可以抑制PR二聚化。迄今为止，最佳非肽类分子钳具有抑制常数K id对于PR为50nM，对于多突变蛋白酶ANAM-11为80nM。PR抑制是选择性的，天冬氨酸蛋白酶肾素和胃蛋白酶不被抑制。
• Synthesen von Peptid-Derivaten der Insulinsequenzen B 1—4, B 1—5 und B 1—8
  作者：Eugen Schnabel、Henning Klostermeyer、Jacques Dahlmans、Helmut Zahn

  DOI：10.1002/jlac.19677070131

  日期：1967.9.27

  Für neue Synthesen der Insulin-B-Kette wurden als kondensationsfähige Fragmente die Peptid-Derivate Z-Phe-Val-Asn-Gln-N2H31 (s. Tab. 1), Z-Phe-Val-Asn-Gln-His-N2H3 (s. Tab. 2) und Z-Phe-Val-Asn-Gln-His(Bzl)-Leu-Cys(Bzl)-Gly (s. Tab. 4) durch schrittweise Kettenverlängerung mit aktivierten Estern der entsprechenden Acylaminosäuren aufgebaut. – Das Pentapeptid-Derivat wurde auch durch Fragmentkondensation

  肽衍生物Z-Phe-Val-Asn-Gln-N 2 H 3 1 （请参见表1），Z-Phe-Val-Asn-Gln-His-N 2 H 3（请参见表2）和Z- Phe-Val-Asn-Gln-His（Bzl）-Leu-Cys（Bzl）-Gly（参见表4）通过与相应酰基氨基酸的活化酯进行逐步扩链。-还通过片段缩合从片段B 1-2和B 3-5合成了五肽衍生物。作为氮将序列B 1-5的末端保护基与叔丁氧羰基或胆固醇氧羰基进行比较（见表2）；与预期相反，这些衍生物在有机溶剂中的溶解度甚至低于苄氧羰基衍生物。在Debye-Scherrer和长期记录的基础上讨论了该现象（请参见表3）。
• Zur Synthese des Glucagons, X. Darstellung der Sequenz 22–29
  作者：Erich Wünsch、Fritz Drees

  DOI：10.1002/cber.19660990119

  日期：1966.1

  N-Phthalyl-L-phenylalanyl-L-valyl-L-glutaminyl-L-tryptophyl-L-leucyl-L-methionyl-L-asparaginyl-O-tert.-butyl-L-threonin-tert.-butylester, die geschützte Teilsequenz 22–29 des Glucagons, wird auf zwei verschiedenen Wegen synthetisiert.

  N-邻苯二甲酰基-L-苯丙氨酰基-L-戊基-L-谷氨酰胺基-L-色氨酸-L-亮氨酰-L-甲硫酰基-L-天冬酰胺基-O-叔丁基-L-苏氨酸-叔丁酯，胰高血糖素的被保护的部分序列22-29以两种不同的方式合成。
• Tetrapeptide analogs
  申请人：Chao Bin

  公开号：US20100190688A1

  公开（公告）日：2010-07-29

  Compounds, compositions and methods for treatment of hyperproliferative diseases, such as cancer are provided.

  提供了用于治疗过度增殖性疾病，如癌症的化合物、组合物和方法。