(S)-2-((tert-butoxycarbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid | 340732-79-8

• 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: (S)-2-((tert-butoxycarbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid
• 英文别名: N-(tert-butoxycarbonyl)-O-prop-2-yn-1-yl-L-tyrosine；N-Boc-O-2-propyn-1-yl-L-tyrosine；(2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-3-(4-prop-2-ynoxyphenyl)propanoic acid
• CAS: 340732-79-8
• 化学式: C₁₇H₂₁NO₅
• 分子量: 319.357
• InChiKey: AYUJBJSCNWVBGS-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-2-((tert-butoxycarbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid 在 N-甲基吗啉 、 N-羟基-7-氮杂苯并三氮唑 、 lithium hydroxide monohydrate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.16h， 生成
  参考文献：
  名称：

  CuAAC Macrocyclization: High Intramolecular Selectivity through the Use of Copper–Tris(triazole) Ligand Complexes

  摘要：

  A range of multivalent heteroaryl ligands, copper sources, and solvent systems have been Investigated for use in CuAAC-mediated macrocyclization reactions. These studies have revealed the key factors governing selectivity for macrocyclization versus dimerization and identified a simple but specific set of reaction conditions capable of efficiently generating a diverse series of drug-like macrocycles at modest dilution in up to 95% yield.

  DOI：

  10.1021/ol200861f
• 作为产物：
  描述：

  2-tert-butoxycarbonylamino-3-[4-(prop-2-ynyloxy)phenyl]propionic acid propargyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以55%的产率得到(S)-2-((tert-butoxycarbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid
  参考文献：
  名称：

  三唑连接甘露糖基和吡喃葡萄糖基氨基酸的合成

  摘要：

  通过铜催化的炔属氨基酸衍生物和含叠氮化物的 [3+2] 环加成，分别在 C-4 和吡喃甘露糖和吡喃葡萄糖衍生物的异头位置合成两种类型的三唑连接糖基氨基酸描述了糖苷。

  DOI：

  10.1055/s-2007-983813

文献信息

• [EN] MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS<br/>[FR] COMPOSÉS MACROCYCLIQUES POUR L'INHIBITION D'INHIBITEURS DE L'APOPTOSE
  申请人：ENSEMBLE THERAPEUTICS

  公开号：WO2013071035A1

  公开（公告）日：2013-05-16

  The invention relates generally to macrocyclic compounds and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of inhibitors of apoptosis (IAPs) and/or are useful in the treatment of medical conditions, such as cancer.

  这项发明通常涉及大环化合物及其治疗用途。更具体地，该发明涉及调节凋亡抑制蛋白（IAPs）活性的大环化合物和/或用于治疗癌症等医疗状况的化合物。
• MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS
  申请人：Ensemble Therapeutics Corp.

  公开号：US20140135270A1

  公开（公告）日：2014-05-15

  There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.

  这里公开了调节凋亡抑制剂（IAPs）活性的化合物，包含所述化合物的药物组合物以及使用本发明的化合物治疗增殖性疾病和凋亡失调疾病的方法，例如癌症。
• 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。
• Oxidative α,ω-diyne coupling as an approach towards novel peptidic macrocycles
  作者：S. Verlinden、N. Geudens、J. C. Martins、D. Tourwé、S. Ballet、G. Verniest

  DOI：10.1039/c5ob01153a

  日期：——

  The Glaser–Hay diyne coupling proved to be an efficient cyclisation approach towards diyne containing peptidic macrocycles.

  Glaser-Hay diyne偶联被证明是一种有效的环化方法，用于制备含有diyne的肽宏环。
• Total Synthesis of Microcystin-LF and Derivatives Thereof
  作者：Ivan Zemskov、Stefan Altaner、Daniel R. Dietrich、Valentin Wittmann

  DOI：10.1021/acs.joc.7b00175

  日期：2017.4.7

  by cyanobacteria. They can be released to the water during harmful algal blooms and are a serious threat to animals and humans. Described is the total synthesis of the cyanotoxin microcystin-LF (MC-LF, 1a) and two derivatives thereof. Deuterated derivative 1b is of interest as an internal standard during MC quantification in biological samples by mass spectrometry and alkyne-labeled 1c can be employed

  微囊藻毒素（MCs）是由蓝细菌产生的高毒性天然产物。它们可能在有害藻华期间释放到水中，并对动物和人类构成严重威胁。描述了氰毒素微囊藻毒素-LF（MC-LF，1a）及其两种衍生物的总合成。氘代衍生物1b作为质谱在生物样品中通过质谱进行MC定量分析时的内标是令人感兴趣的，炔烃标记的1c可用于通过点击化学与含叠氮化物的报告分子进行毒素衍生化，或用作基于活性的探针来鉴定相互作用伙伴。的应用叔丁基酯保护基赤-β- d-甲基天冬氨酸和γ- d-谷氨酸是无异构化合成的关键。合成MC-LF的分析数据与天然产物的真实样品的分析数据相同。所有衍生物1a – c被确定为具有相似活性的强力蛋白磷酸酶1抑制剂。