methyl N^ω-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-argininate

• 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: methyl N^ω-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-argininate
• 英文别名: methyl N^ω-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-arginate；H-Arg(Pbf)-OMe；methyl (2S)-2-amino-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]pentanoate
• 化学式: C₂₀H₃₂N₄O₅S
• 分子量: 440.564
• InChiKey: WAVIIAKQONVPGL-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  155
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl N^ω-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-argininate 在 barium hydroxide octahydrate 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 5.34h， 生成 (2S)-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-[[(2S)-3-methyl-1-[(2-methylpropan-2-yl)oxy]-1-oxobutan-2-yl]carbamoylamino]pentanoic acid
  参考文献：
  名称：

  Mechanistic Analysis of Muraymycin Analogues: A Guide to the Design of MraY Inhibitors

  摘要：

  The systematic structure activity relationship (SAX) of the muraymycins (MRYs) using an Ugi four-component reaction (U4CR) was investigated. The impact of the lipophilic substituent on antibacterial activity was significant, and the analogues 8 and 9 having a lipophilic side chain exhibited good activity against a range of Gram-positive bacterial pathogens, including MRSA and VRE. Further investigation of compounds 8 and 9 revealed these analogues to be selective inhibitors of the MraY transferase and nontoxic to HepG2 cells. The SAX of the accessory urea peptide moiety indicated that it could be simplified. Our SAX study of the MRYs suggests a probable mechanism for inhibition of the MraY, where the inner moiety of the urea dipeptide motif interacts with the carbohydrate recognition domain in the cytoplasmic loop S. The predicted binding model would provide further direction toward the design of potent MraY inhibitors. This study has set the stage for the generation of novel antibacterial "lead" compounds based on MRYs.

  DOI：

  10.1021/jm200906r
• 作为产物：
  描述：

  Boc-Arg(Pbf)-OH 在 哌啶 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以7.61 g的产率得到methyl N^ω-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-argininate
  参考文献：
  名称：

  小分子CD4模拟物与聚乙二醇单元作为HIV进入抑制剂的杂种。

  摘要：

  CD4模拟物是抑制gp120与CD4相互作用的小分子。我们已经开发了几种CD4模拟物。在本文中，合成了由具有长烷基链或通过自裂解接头连接的PEG单元的CD4模拟物组成的杂合分子。在抗HIV活性方面，用PEG单元修饰似乎比用长烷基链修饰更合适。因此，开发了具有通过不可裂解的接头连接的PEG单元的CD4模拟物的杂合分子，并显示出高的抗HIV活性和低的细胞毒性。在恒河猴中的药代动力学研究中，杂合化合物的PK曲线比母体化合物更有效，而肌肉注射比静脉注射是维持CD4模拟物高血药浓度的更有用的给药途径。

  DOI：

  10.1021/acs.jmedchem.0c01153

文献信息

• [EN] INHIBITORS OF GROWTH FACTOR ACTIVATION ENZYMES<br/>[FR] INHIBITEURS D'ENZYMES D'ACTIVATION DE FACTEUR DE CROISSANCE
  申请人：UNIV WASHINGTON

  公开号：WO2016144654A1

  公开（公告）日：2016-09-15

  The present invention generally relates to compounds that are useful for inhibiting one or more of hepatocyte growth factor activator, matriptase, hepsin, Factor Xa, or thrombin. The present invention also relates to various methods of using the inhibitor compounds including treating a malignancy, a pre-malignant condition, or cancer by administering an effective amount of the inhibitor to a subject in need thereof.

  本发明通常涉及对抑制肝细胞生长因子激活剂、麦曲丝蛋白、赫普星、Xa因子或凝血酶等的化合物有用的化合物。本发明还涉及使用抑制剂化合物的各种方法，包括通过向需要的受试者施用有效量的抑制剂来治疗恶性肿瘤、癌前病变或癌症。
• NOVEL SMALL MOLECULE DNAK INHIBITORS
  申请人：Sturgess Michael Alan

  公开号：US20100087466A1

  公开（公告）日：2010-04-08

  Methods of inhibiting HSP70 proteins, agents causing the inhibition of HSP70 proteins, and the effects of such inhibition on cell proliferation. Anti-microbial agents comprising small molecules, or pharmaceutical salts thereof, disclosed herein and further methods of use thereof are also disclosed. The disclosed small molecules, or pharmaceutical salts thereof, are effective in inhibiting microbial chaperone activity in microbes, such as homologs of HSP70. The disclosed small molecules, or pharmaceutical salts thereof, are also effective for the therapeutic treatment of cancer.

  抑制HSP70蛋白的方法，导致抑制HSP70蛋白的药剂，以及这种抑制对细胞增殖的影响。本文还披露了包含小分子或其药用盐的抗微生物药剂，以及其进一步的使用方法。所披露的小分子或其药用盐对微生物中的分子伴侣活性具有抑制作用，例如HSP70同源物。所披露的小分子或其药用盐还对癌症的治疗治疗有效。
• NO-RELEASING GUANIDINE-CHROMENE CONJUGATES
  申请人：Euclises Pharmaceuticals, Inc.

  公开号：US20150197500A1

  公开（公告）日：2015-07-16

  The present disclosure provides NO-releasing guanidine-chromene conjugates, having the structure of Formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 10 , and L are as defined in the detailed description; pharmaceutical compositions comprising at least one of the compounds of Formula (I); and methods useful for healing wounds, preventing and treating cancer, or treating actinic keratosis, cystic fibrosis, acne, or a disease mediated by arginine deficiency using a compound of Formula (I).

  本公开提供NO释放的胍基-色酮共轭物，具有以下结构的化学式(I)：其中R1、R2、R3、R4、R10和L如详细说明中定义；包含至少一种化合物的药物组合物的制剂；以及使用化合物(I)治愈伤口、预防和治疗癌症、或治疗日光性角化症、囊性纤维化、痤疮或由精氨酸缺乏介导的疾病的有用方法。
• Synthetic studies of cyclic peptides stephanotic acid methyl ester, celogentin C, and moroidin
  作者：Lei Li、Weimin Hu、Yanxing Jia

  DOI：10.1016/j.tet.2014.05.082

  日期：2014.10

  An account of the total synthesis of stephanotic acid methyl ester and celogentin C is presented. The present synthesis features a tandem asymmetric Michael addition/bromination sequence for the synthesis of leucine-tryptophan moiety, and an oxidative coupling reaction to form the tryptophan-imidazole linkage. Moreover, the total synthesis of moroidin had also been studied, and three different synthetic

  提出了对单链烷酸甲酯和celogentin C的总合成的说明。本发明的特征在于用于合成亮氨酸-色氨酸部分的串联不对称迈克尔加成/溴化序列，以及形成色氨酸-咪唑键的氧化偶联反应。此外，还研究了莫罗定的全合成，并研究了三种不同的合成方法来构建莫罗定的右手环。
• Oxidative peptide bond formation of glycine–amino acid using 2-(aminomethyl)malononitrile as a glycine unit
  作者：Xiaoling Wang、Jing Li、Yujiro Hayashi

  DOI：10.1039/d1cc00130b

  日期：——

  of glycine–amino acid was synthesized by coupling of substituted 2-(aminomethyl)malononitrile as a C-terminal glycine unit and N-terminal amine using CsOAc and O2 in an aqueous solution. This is a coupling reagent-free and catalyst-free peptide synthesis via oxidative amide bond formation. Various tripeptides and tetrapeptides were synthesized efficiently and the sulfide moiety is inert even under

  甘氨酸-氨基酸的酰胺键是通过在水溶液中使用CsOAc和O 2偶联取代的2-（氨基甲基）丙二腈作为C末端甘氨酸单元和N末端胺而合成的。这是通过氧化酰胺键形成的无偶联试剂和无催化剂的肽合成。有效地合成了各种三肽和四肽，并且即使在氧气气氛下，硫化物部分也是惰性的。