N-Boc-3-氟-L-酪氨酸 | 125218-33-9

• 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-Boc-3-氟-L-酪氨酸
• 英文名称: Boc-Tyr(m-F)-OH
• 英文别名: (S)-2-((tert-butoxycarbonyl)amino)-3-(3-fluoro-4-hydroxyphenyl)propanoic acid (N-Boc-3-fluorotyrosine)；3-fluoro-N-Boc-L-tyrosine；N-Boc-3-Fluoro-L-tyrosine；(2S)-3-(3-fluoro-4-hydroxyphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 125218-33-9
• 化学式: C₁₄H₁₈FNO₅
• 分子量: 299.299
• InChiKey: PIDYYTCMUSVKTJ-JTQLQIEISA-N

物化性质

• 沸点：
  468.8±45.0 °C(Predicted)
• 密度：
  1.294±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  6

安全信息

• 危险性防范说明：
  P233,P260,P261,P264,P271,P280,P302+P352,P304,P304+P340,P305+P351+P338,P312,P321,P332+P313,P337+P313,P340,P362,P403,P403+P233,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-Boc-3-氟-L-酪氨酸 在 碘苯二乙酸 作用下， 以 乙腈 为溶剂， 反应 6.0h， 以17%的产率得到tert-butyl (7-fluoro-2,8-dioxo-1-oxaspiro[4.5]deca-6,9-dien-3-yl)carbamate
  参考文献：
  名称：

  Synthesis and Site-Specific Incorporation of Red-Shifted Azobenzene Amino Acids into Proteins

  摘要：

  A series of red-shifted azobenzene amino acids were synthesized in moderate-to-excellent yields via a two-step procedure in which tyrosine derivatives were first oxidized to the corresponding quinonoidal spirolactories followed by ceric Ammonium nitrate-catalyzed azo formation with the substituted phenylhydrazines. The resulting azobenzene-Alanine derivatives exhibited efficient trans/cis photoswitching upon irradiation With a blue (448 nm) or green (530 nm) LED light Moreover, nine superfolder green fluorescent protein (sfGFP) Mutants carrying the atobenzene-alanine analogues Were expressed in E. coli in good yields via amber codon suppression with an orthogonal tRNA/Py1RS pair, and one of the mutants showed durable photoswitching with the LED light.

  DOI：

  10.1021/acs.orglett.5b03268
• 作为产物：
  描述：

  2-氟苯酚 在 tyrosine phenol lyase 、 ammonium acetate 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 为溶剂， 生成 N-Boc-3-氟-L-酪氨酸
  参考文献：
  名称：

  使用非天然氨基酸探测酮类固醇异构酶活性位点氧阴离子空穴氢键的能量学

  摘要：

  氢键在酶活性位点中无处不在，在反应过程中提供结合相互作用和稳定底物基团上的电荷重排。但是，了解它们相对于水溶液中氢键的催化贡献的起源和大小仍然很困难，部分原因是在传统定点诱变实验的能量解释中遇到了复杂性。已经建议酮类固醇异构酶和其他酶的活性位点氢键基团通过“短、强”或“低势垒”氢键提供能量稳定，这些氢键是由于它们的 pKa 或质子亲和力与跃迁的匹配而形成的状态。还提出，相对于水溶液，酮类固醇异构酶和其他酶活性位点提供静电环境，导致对基态到过渡态电荷重排的更大能量反应（即更大的“敏感性”），从而提供催化作用相对于水中的相应反应。为了测试这些模型，我们在酮类固醇异构酶 (KSI) 氧阴离子孔中用氟酪氨酸 (F-Tyr's) 取代酪氨酸，以系统地改变活性位点氢键供体的质子亲和力，同时最大限度地减少空间或结构影响。我们发现，内在 F-Tyr 酸度增加 40 倍不会导致与三种不同底物反应的活性发生显着变化。F-Tyr

  DOI：

  10.1021/ja413174b

文献信息

• TYROSINE AMIDE DERIVATIVES AS RHO- KINASE INHIBITORS
  申请人：CHIESI FARMACEUTICI S.P.A.

  公开号：US20180215758A1

  公开（公告）日：2018-08-02

  Bicyclic dihydropyrimidine-carboxamide compounds of formula I described herein inhibit Rho Kinase and may be used for the treatment of many disorders associated with ROCK enzymes mechanisms, such as pulmonary diseases including asthma, chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and pulmonary arterial hypertension (PAH).

  本文描述的式I的双环二氢嘧啶羧酰胺化合物抑制Rho激酶，可用于治疗与ROCK酶机制相关的许多疾病，如包括哮喘、慢性阻塞性肺疾病（COPD）、特发性肺纤维化（IPF）和肺动脉高压（PAH）在内的肺部疾病。
• 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。
• Amino acids and peptides. X. Leu-enkephalin analogues containing a fluorinated aromatic amino acid.
  作者：Mitsuko MAEDA、Koichi KAWASAKI、Joe WATANABE、Hiroshi KANETO

  DOI：10.1248/cpb.37.826

  日期：——

  Leu-enkephalin analogues containing a fluorinated derivative of Tyr1 or Phe4 were synthesized by the solid-phase method and their biological activities were studied. Fluorination of the p-position of Phe4 resulted in a marked potentiation of the inhibitory effect on electrically induced contractions of guinea-pig ileum (GPI) and mouse vas deferens (MVD). On the other hand, substitution of fluorine for the hydroxyl group of Tyr1 or introduction of a trifluoromethyl group at the p-position of Phe4 markedly reduced the inhibitory effect in both preparations. Fluorination of other positions of Tyr1 and Phe4 did not cause substantial changes in the activities as compared with Leu-enkephalin.

  通过固相法合成了含有 Tyr1 或 Phe4 含氟衍生物的亮氨酸脑啡肽类似物，并研究了它们的生物活性。对 Phe4 的 p 位进行氟化可明显增强对电诱导的豚鼠回肠（GPI）和小鼠输精管（MVD）收缩的抑制作用。另一方面，用氟取代 Tyr1 的羟基或在 Phe4 的 p 位上引入三氟甲基，可明显降低这两种制剂的抑制作用。与亮氨酸脑啡肽相比，Tyr1 和 Phe4 其他位置的氟化并没有引起活性的实质性变化。
• Studies on Analgesic Oligopeptides. VII. Solid Phase Synthesis and Biological Properties of Tyr-D-Arg-Phe-.BETA.Ala-NH2 and its Fluorinated Aromatic Amino Acid Derivatives.
  作者：Yusuke SASAKI、Akihiro AMBO、Kenji SUZUKI

  DOI：10.1248/cpb.39.2316

  日期：——

  Tyr-D-Arg-Phe-beta Ala-NH2 (I) and its six fluorinated analogs were synthesized. Their opioid receptor binding properties were examined in vitro and their analgesic activity in vivo using the mouse writhing test. It was found that I was one of the most selective and potent mu-receptor agonists reported to date. [Tyr(2F)1](VI) and [Tyr(3F)1](V) derivatives of I showed similar biological properties to those of I. Since

  合成了Tyr-D-Arg-Phe-βAla-NH2（I）及其六个氟化类似物。使用小鼠扭体试验对它们的阿片样物质受体结合特性进行了体外检查，并在体内对其进行了镇痛作用。人们发现我是迄今为止报道的最有选择性和最有力的mu受体激动剂之一。I的[Tyr（2F）1]（VI）和[Tyr（3F）1]（V）衍生物显示出与I相似的生物学特性。由于这些肽具有抗酶促降解作用，因此，它们被认为是优异的试剂。受体在体内和体外介导生物学特性的功能研究。
• [EN] EFFLUX PUMP INHIBITORS<br/>[FR] INHIBITEURS DE POMPE D'ECOULEMENT
  申请人：MICROCIDE PHARMACEUTICALS, INC.

  公开号：WO1999037667A1

  公开（公告）日：1999-07-29

  (EN) Compounds are described which have efflux pump inhibitor activity. Also described are methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.(FR) L'invention concerne des composés présentant une activité d'inhibiteur de pompe d'écoulement. L'invention concerne également des méthodes d'utilisation de ces composés inhibiteurs et des compositions pharmaceutiques renfermant de tels composés.

  （中文翻译）描述了具有外排泵抑制剂活性的化合物。还描述了使用这种外排泵抑制剂化合物的方法和包括这种化合物的药物组合物。