N-(苄氧羰基)-L-酪氨酸叔丁酯 | 16881-33-7

• 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: N-(苄氧羰基)-L-酪氨酸叔丁酯
• 中文别名: CBZ-L-酪氨酸叔丁酯一水化合物；CBZ-L-酪氨酸叔丁酯
• 英文名称: (S)-tert-butyl 2-(((benzyloxy)carbonyl)amino)-3-(4-hydroxyphenyl)propanoate
• 英文别名: Z-Tyr-OtBu；tert-butyl (2S)-3-(4-hydroxyphenyl)-2-(phenylmethoxycarbonylamino)propanoate
• CAS: 16881-33-7
• 化学式: C₂₁H₂₅NO₅
• 分子量: 371.433
• InChiKey: ZRMZOLWSSDIXDQ-SFHVURJKSA-N

物化性质

• 熔点：
  86-88℃
• 沸点：
  543.8±50.0 °C(Predicted)
• 密度：
  1.186±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-(苄氧羰基)-L-酪氨酸叔丁酯 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 生成 L-酪氨酸叔丁酯
  参考文献：
  名称：

  t-Butyl Esters of Amino Acids and Peptides and their Use in Peptide Synthesis¹

  摘要：

  DOI：

  10.1021/ja01498a032
• 作为产物：
  描述：

  N-苄氧羰基-L-酪氨酸 、 异丁烯 在 硫酸 作用下， 生成 N-(苄氧羰基)-L-酪氨酸叔丁酯
  参考文献：
  名称：

  t-Butyl Esters of Amino Acids and Peptides and their Use in Peptide Synthesis¹

  摘要：

  DOI：

  10.1021/ja01498a032

文献信息

• [EN] NOVEL GLP-1 RECEPTOR MODULATORS<br/>[FR] NOUVEAUX MODULATEURS DU RÉCEPTEUR GLP-1
  申请人：RECEPTOS INC

  公开号：WO2014201172A1

  公开（公告）日：2014-12-18

  Compounds are provided that modulate the glucagon-like peptide 1 (GLP-1) receptor, as well as methods of their synthesis, and methods of their therapeutic and/or prophylactic use. Such compounds can act as modulators or potentiators of GLP-1 receptor on their own, or with incretin peptides such as GLP-1(7-36) and GLP-1(9-36), or with peptide-based therapies, such as exenatide and liraglutide, and have the following general structure (where "(Ⅰ)" represents either or both the R and S form of the compound): where A, B, C, Y1, Y2, Z, R1, R2, R3, R4, R5, W1, n, p and q are as defined herein.

  提供了一些化合物，这些化合物可以调节胰高血糖素样肽1（GLP-1）受体，以及它们的合成方法和治疗性及/或预防性使用方法。这些化合物可以单独作为GLP-1受体的调节剂或增强剂，或者与肠促胰岛素肽（如GLP-1(7-36)和GLP-1(9-36)）一起使用，或者与基于肽的治疗方法（如艾塞那肽和利拉鲁肽）一起使用，并具有以下一般结构（其中"(Ⅰ)"代表化合物的R和S形式中的一个或两个）：其中A、B、C、Y1、Y2、Z、R1、R2、R3、R4、R5、W1、n、p和q如本文所述定义。
• Tyrosine alkoxyguanidines as integrin inhibitors
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US06344484B1

  公开（公告）日：2002-02-05

  The present invention relates to novel tyrosine alkoxyguanidine compounds that are inhibitors of alpha V (&agr;v) integrins, for example &agr;v&bgr;3 and &agr;v&bgr;5 integrins, their pharmaceutically acceptable salts, and pharmaceutical compositions thereof. The compounds may be used in the treatment of pathological conditions mediated by &agr;v&bgr;3 and &agr;v&bgr;5 integrins, including conditions such as tumor growth, metastasis, restenosis, osteoporosis, inflammation, macular degeneration, diabetic retinopathy, and rheumatoid arthritis. The compounds have the general formula: where R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, m and n are defined herein.

  本发明涉及新颖的酪氨酸烷氧基胍化合物，它们是αV（αv）整联蛋白的抑制剂，例如αvβ3和αvβ5整联蛋白，其药用可接受的盐以及由此构成的药物组合物。这些化合物可用于治疗由αvβ3和αvβ5整联蛋白介导的病理状况，包括肿瘤生长、转移、再狭窄、骨质疏松症、炎症、黄斑变性、糖尿病视网膜病变和类风湿性关节炎。这些化合物具有以下通用公式： 其中R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、m和n在此文中定义。
• Deprotection of t-Butyl Esters of Amino Acid Derivatives by Nitric Acid in Dichloromethane
  作者：Paolo Strazzolini、Massimo Scuccato、Angelo G Giumanini

  DOI：10.1016/s0040-4020(00)00280-5

  日期：2000.5

  selected N-Z-derivatives of natural amino acid esters was investigated. The method was found to work effectively with alanine, phenylalanine, serine and the dipeptide aspartame, but the reagent brought about a number of unwanted transformations with tyrosine, methionine and tryptophan. Suitable protection of functions present in the latter ones allowed selective ester dealkylation, but tyrosine underwent

  的去保护方法的延伸吨使用HNO -butylated羧基官能3在CH 2氯2到多个适当选择的Ñ的天然氨基酸酯-Z-衍生物进行了研究。发现该方法可与丙氨酸，苯丙氨酸，丝氨酸和二肽阿斯巴甜一起有效地工作，但是该试剂带来了许多不需要的酪氨酸，蛋氨酸和色氨酸转化。对后者中存在的官能团的适当保护允许选择性酯脱烷基，但是酪氨酸不可避免地需要进行快速的初步环硝化。
• Novel Non-Peptide GPIIb/IIIa Antagonists. Synthesis and Biological Activities of 2-[4-[2-(4-Amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiperazinyl] acetic Acids.
  作者：Shuji KITAMURA、Hideto FUKUSHI、Toshio MIYAWAKI、Masaki KAWAMURA、Zen-ichi TERASHITA、Hirosada SUGIHARA、Takehiko NAKA

  DOI：10.1248/cpb.49.258

  日期：——

  To improve the in vitro and in vivo potency of our first low molecular weight GPIIb/IIIa antagonist 1 (TAK-029), a series of 2-[4-[2-(4-amidinobenzoylamino)-2-(substituted)acetyl]-3-(2-methoxy-2-oxoethyl)-2-oxopiperazinyl]acetic acids were synthesized through modification of the glycine moiety of 1 and evaluated for their ability to inhibit in vitro adenosine 5'-diphosphate (ADP)-induced platelet aggregation of guinea pig platelet rich plasma (PRP). Among the compounds examined, the (3S, 2S)-4-methoxyphenylalanine derivative 4h showed the most potent antagonistic activity with an IC50 value of 13 nM. Dose-dependent inhibition of ex vivo platelet aggregation was achieved with oral administration of 4h (0.3-1.0 mg/kg) to guinea pigs. Complete inhibition was observed for up to 8 h, and 43% inhibition could still be observed 24 h after oral administration of 1.0 mg/kg. The long-lasting antiplatelet effect of 4h suggests that 4h would be suitable for once-a-day dosing. Structure-activity relationships (SAR) were examined in the series of the phenylalanine derivatives. An increase in the electron density around the 4-position of the phenyl ring of the phenylalanine moiety led to an increase in the antiplatelet activity, suggesting the existence of a hydrophobic and electrostatic interaction site in addition to the ionic binding sites in the GPIIb/IIIa.

  为了提高我们首个低分子量GPIIb/IIIa拮抗剂1（TAK-029）的体外和体内活性，通过改造1的甘氨酸部分，合成了一系列2-[4-[2-(4-脒基苯甲酰氨基)-2-(取代)乙酰基]-3-(2-甲氧基-2-氧代乙基)-2-氧代哌嗪基]乙酸，并评估了它们抑制体外腺苷5'-二磷酸（ADP）诱导的豚鼠富含血小板血浆（PRP）聚集的能力。在所研究的化合物中，（3S，2S）-4-甲氧基苯丙氨酸衍生物4h显示出最强的拮抗活性，IC50值为13 nM。通过口服给药4h（0.3-1.0 mg/kg）给豚鼠，实现了对体外血小板聚集的剂量依赖性抑制。完全抑制可持续长达8小时，并且在口服1.0 mg/kg后24小时仍可观察到43%的抑制效果。4h的持久抗血小板效应表明4h适合每日一次给药。在苯丙氨酸衍生物系列中考察了构效关系（SAR）。苯丙氨酸部分苯环4位周围的电子密度增加导致抗血小板活性增强，这表明除了离子结合位点外，GPIIb/IIIa还存在一个疏水性和静电相互作用位点。
• Synthesis of RGD Analogs as Potential Vectors for Targeted Drug Delivery
  作者：Ji Jiang、Wei Wang、David C. Sane、Binghe Wang

  DOI：10.1006/bioo.2001.1227

  日期：2001.12

  RGD analogs bind to integrin receptors with high affinity and therefore have the potential to be used as vectors for the targeted delivery of pharmaceutical agents to designated sites. Critical to this application is the ability to synthesize RGD analogs with different side chain functional groups that allow for the ready tethering of pharmaceutical agents without sacrificing their affinity for the

  RGD类似物以高亲和力与整联蛋白受体结合，因此有潜力用作将药物靶向递送至指定部位的载体。对于该应用而言，至关重要的是具有不同侧链官能团的RGD类似物的合成能力，从而可以方便地束缚药物，而又不会显着牺牲其对靶受体的亲和力。制备了一系列打算用作药物递送载体的RGD类似物，并评估了它们通过结合糖蛋白IIb / IIIa抑制血小板聚集的能力。其中，化合物11对ADP活化的血小板的IC50最低。发现这种RGD类似物可以很好地耐受带有各种官能团如酰胺，胺，酯，受保护的胺和聚乙二醇的侧链修饰。具有聚（乙二醇）侧链修饰的化合物保留了对糖蛋白IIb / IIIa的高亲和力（IC50 150 nM）这一事实表明，在不显着牺牲其对RGD类似物的亲和力的情况下，可以将相当大的药剂与这些RGD类似物束缚。预期的受体。