(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid | 1204595-05-0

• 物质功能分类: 生物 - 细胞培养 - 添加剂
• 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-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid
• 英文别名: Fmoc-L-Tyr(propargyl)-OH；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-prop-2-ynoxyphenyl)propanoic acid
• CAS: 1204595-05-0
• 化学式: C₂₇H₂₃NO₅
• 分子量: 441.483
• InChiKey: COXQVDBEMQQDOE-VWLOTQADSA-N

物化性质

• 沸点：
  678.6±55.0 °C(Predicted)
• 密度：
  1.282±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  33
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 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,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid 在 三乙基硅烷 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 1,2-二氯乙烷 、 甲苯 为溶剂， 生成 (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)(methyl)amino)-3-(4-(prop-2-ynyloxy)phenyl)propanoic acid
  参考文献：
  名称：

  The Discovery of Macrocyclic XIAP Antagonists from a DNA-Programmed Chemistry Library, and Their Optimization To Give Lead Compounds with in Vivo Antitumor Activity

  摘要：

  Affinity selection screening of macrocycle libraries derived from DNA-programmed chemistry identified MAP BIR2 and BIR3 domain inhibitors that displace bound pro-apoptotic caspases. X-ray cocrystal structures of key compounds with XIAP BIR2 suggested potency-enhancing structural modifications. Optimization of dimeric macrocycles with similar affinity for both domains were potent proapoptotic agents in cancer cell lines and efficacious in shrinking tumors in a mouse xenograft model.

  DOI：

  10.1021/jm501892g
• 作为产物：
  描述：

  在 碳酸氢钠 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 22.0h， 生成 (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-(prop-2-yn-1-yloxy)phenyl)propanoic acid
  参考文献：
  名称：

  Oxidative α,ω-diyne coupling as an approach towards novel peptidic macrocycles

  摘要：

  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。

  DOI：

  10.1039/c5ob01153a

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

  公开号：WO2013071027A1

  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，以及在治疗癌症等医疗状况中有用的大环化合物。
• Identification and Validation of New Interleukin-2 Ligands Using DNA-Encoded Libraries
  作者：Adrián Gironda-Martínez、Émile M. D. Gorre、Luca Prati、Jean-François Gosalbes、Sheila Dakhel、Samuele Cazzamalli、Florent Samain、Etienne J. Donckele、Dario Neri

  DOI：10.1021/acs.jmedchem.1c01693

  日期：2021.12.9

  IL2-based therapeutics which do not interact with the alpha subunit of the IL2 receptor (CD25) as this protein is primarily found on immunosuppressive regulatory T cells (Tregs). Screenings of a new DNA-encoded library, comprising 669,240 members, provided a novel series of IL2 ligands, subsequently optimized by medicinal chemistry. One of these molecules (compound 18) bound to IL2 with a dissociation constant

  白细胞介素 2 (IL2) 是一种促炎细胞因子，在免疫中起着至关重要的作用，越来越多地用于治疗应用。人们越来越关注开发不与 IL2 受体 (CD25) 的 α 亚基相互作用的基于 IL2 的治疗剂，因为这种蛋白质主要存在于免疫抑制调节性 T 细胞 (T regs ) 上。筛选包含 669,240 个成员的新 DNA 编码文库，提供了一系列新的 IL2 配体，随后通过药物化学进行了优化。这些分子之一（化合物18) 以 0.34 μM 的解离常数与 IL2 结合，能够在尺寸排阻色谱中与 IL2 形成动力学稳定的复合物，并识别 CD25 结合位点，如与 NARA1 抗体的竞争实验所证明的那样。化合物18和该系列的其他成员可能代表了发现有效的 IL2 活性小分子调节剂的起点，消除了与 CD25 的结合。
• MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS
  申请人：Ensemble Therapeutics

  公开号：US20140309265A1

  公开（公告）日：2014-10-16

  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.

  本发明涉及大环化合物及其治疗用途。更具体地说，本发明涉及调节凋亡抑制剂(IAPs)活性和/或用于治疗医学状况（如癌症）的大环化合物。
• In Vitro Membrane Permeation Studies and in Vivo Antinociception of Glycosylated Dmt¹-DALDA Analogues
  作者：Steven Ballet、Cecilia Betti、Alexandre Novoa、Csaba Tömböly、Carsten Uhd Nielsen、Hans Christian Helms、Anna Lesniak、Patrycja Kleczkowska、Nga N. Chung、Andrzej W. Lipkowski、Birger Brodin、Dirk Tourwé、Peter W. Schiller

  DOI：10.1021/ml4004765

  日期：2014.4.10

  In this study the mu opioid receptor (MOR) ligands DALDA (Tyr-D-Arg-Phe-Lys-NH2) and Dmt(1)-DALDA (Dmt-D-Arg-Phe-Lys-NH2, Dmt = 2',6'-dimethyltyrosine) were glycosylated at the N- or C-terminus. Subsequently, the modified peptides were subjected to in vitro and in vivo evaluation. In contrast to the N-terminally modified peptide (3), all peptide analogues derivatized at the C-terminus (4-7) proved to possess high affinity and agonist potency at both MOR and DOR (delta opioid receptor). Results of the Caco-2 monolayer permeation, as well as in vitro blood-brain barrier model experiments, showed that, in the case of compound 4, the glycosylation only slightly diminished the lumen-to-blood and blood-to-lumen transport. Altogether, these experiments were indicative of transcellular transport but not active transport. In vivo assays demonstrated that the peptides were capable of (i) crossing the blood-brain barrier (BBB) and (ii) activating both the spinal ascending as well as the descending opioid pathways, as determined by the tail-flick and hot-plate assays, respectively. In contrast to the highly selective MOR agonist Dmt(1)-DALDA 1, compounds 4-7 are mixed MOR/DOR agonists, expected to produce reduced opioid-related side effects.