Fmoc-Ala-Wang resin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: Fmoc-Ala-Wang resin
• 英文别名: (1R*,2R*,4S*)-N1-[(5-Chloroindol-2-yl)carbonyl]-4-ethoxycarbonyl-N2-[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]-1,2-cyclohexanediamine；ethyl (1S,3R,4R)-4-[(5-chloro-1H-indole-2-carbonyl)amino]-3-[(5-methyl-6,7-dihydro-4H-[1,3]thiazolo[5,4-c]pyridine-2-carbonyl)amino]cyclohexane-1-carboxylate
• 化学式: C₁₈H₁₆NO₃Pol
• 分子量: 544.1
• InChiKey: LMABBMHHZJCBNM-BOUXLOLZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Fmoc-Ala-Wang resin 在 sodium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 12.0h， 以800 mg的产率得到(1S,3R,4R)-4-{[(5-chloroindol-2-yl)carbonyl]amino}-3-{[(5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridin-2-yl)carbonyl]amino}cyclohexanecarboxylic acid
  参考文献：
  名称：

  Discovery of N-[(1R,2S,5S)-2-{[(5-chloroindol-2-yl)carbonyl]amino}-5-(dimethylcarbamoyl)cyclohexyl]-5-methyl-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine-2-carboxamide hydrochloride: A novel, potent and orally active direct inhibitor of factor Xa

  摘要：

  In the early 1990's, we reported on the low-molecular selective fXa inhibitor DX-9065a having two amidino groups. However, it had poor oral bioavailability due to its strong basic amidino groups. To obtain fXa inhibitors with improved oral bioavailability, we investigated various non-amidino fXa inhibitors and finally discovered cis-1,2-diaminocyclohexane derivative 4c to have potent fXa inhibition, promising anticoagulant activity, and good oral bioavailability, compared with amidino compound DX-9065a. In addition, we will discuss the influence of the third substituent on the cyclohexane ring on anti-fXa activity, anticoagulant activity, PK profile, and lipophilicity. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.12.037
• 作为产物：
  描述：

  Fmoc-L-丙氨酸 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 N,N'-二异丙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 Fmoc-Ala-Wang resin
  参考文献：
  名称：

  [EN] 5-SUBSTITUTED-2-IMINO-THIAZOLIDINONE COMPOUNDS AND THEIR USE AS INHIBITORS OF BACTERIAL INFECTION
  [FR] COMPOSÉS 2-IMINO-THIAZOLIDINONE SUBSTITUÉS EN POSITION 5 ET LEUR UTILISATION COMME INHIBITEURS D'INFECTION BACTÉRIENNE

  摘要：

  公开号：

  WO2009137133A3

文献信息

• Compositions and Methods for Preventing or Treating Diseases, Conditions, or Processes Characterized by Aberrant Fibroblast Proliferation and Extracellular Matrix Deposition
  申请人：MOERAE MATRIX, INC.

  公开号：US20160136234A1

  公开（公告）日：2016-05-19

  The described invention provides compositions and methods for reducing progression of a fibrosis in a tissue of a subject selected from liver, kidney or vascular fibrosis, the progression of the fibrosis being characterized by aberrant fibroblast proliferation and extracellular matrix deposition in the tissue. The method includes administering a therapeutic amount of a pharmaceutical composition containing a polypeptide having the amino acid sequence YARAAARQARAKALARQLGVAA (SEQ ID NO: 1) or functional equivalent thereof, and a pharmaceutically acceptable carrier, wherein the therapeutic amount of the polypeptide is effective to reduce progression of the fibrosis, to treat remodeling of the tissue, or a combination thereof.

  描述的发明提供了一种用于减少主体选定组织中的纤维化进展的组成和方法，该选定组织来自肝纤维化、肾纤维化或血管纤维化，纤维化的进展在组织中以异常成纤维细胞增殖和细胞外基质沉积为特征。该方法包括施用含有具有氨基酸序列YARAAARQARAKALARQLGVAA（SEQ ID NO: 1）或其功能等效物的多肽的药物治疗量，以及药学上可接受的载体，其中多肽的治疗量有效于减少纤维化的进展，治疗组织的重塑，或其组合。
• Solid-Phase Synthesis of Oxetane Modified Peptides
  作者：Jonathan D. Beadle、Astrid Knuhtsen、Alex Hoose、Piotr Raubo、Andrew G. Jamieson、Michael Shipman

  DOI：10.1021/acs.orglett.7b01466

  日期：2017.6.16

  Solid-phase peptide synthesis (SPPS) is used to create peptidomimetics in which one of the backbone amide C═O bonds is replaced by a four-membered oxetane ring. The oxetane containing dipeptide building blocks are made in three steps in solution, then integrated into peptide chains by conventional Fmoc SPPS. This methodology is used to make a range of peptides in high purity including backbone modified

  固相肽合成（SPPS）用于创建拟肽，其中主链酰胺C═O键之一被四元氧杂环丁烷环取代。含氧杂环丁烷的二肽结构单元可在溶液中分三步制备，然后通过常规的Fmoc SPPS整合到肽链中。该方法用于制备一系列高纯度的肽，包括九肽缓激肽的主链修饰衍生物以及Met-和Leu-脑啡肽。
• Energetic contribution to both acidity and conformational stability in peptide models
  作者：Vladimir Kubyshkin、Patrick Durkin、Nediljko Budisa

  DOI：10.1039/c5nj03611a

  日期：——

  The acidity difference of the amide rotamers has been revised for a large set ofN-acetyl amino acids.

  酰胺构象异构体的酸度差异已经针对大量的N-乙酰氨基酸进行了修订。
• Plasmodium falciparum subtilisin-like protease 1: discovery of potent difluorostatone-based inhibitors
  作者：Simone Giovani、Maria Penzo、Stefania Butini、Margherita Brindisi、Sandra Gemma、Ettore Novellino、Giuseppe Campiani、Michael J. Blackman、Simone Brogi

  DOI：10.1039/c5ra01170a

  日期：——

  available drugs to treat malaria are often ineffective due to the acquisition of drug resistance. In this context, drugs with innovative modes of action and no liability to cross-resistance are urgently needed. Recently, subtilisin-like protease 1, a P. falciparum serine protease involved in merozoite egress from red blood cells and invasion, has been identified as potential drug target. We describe

  由于获得抗药性，目前可用于治疗疟疾的药物通常无效。在这种情况下，迫切需要具有创新作用方式且对交叉耐药性不承担责任的药物。最近，枯草杆菌蛋白酶样蛋白酶1，一种恶性疟原虫丝氨酸蛋白酶，参与了裂殖子从红细胞中逸出并侵入，已被确定为潜在的药物靶标。我们在本文中描述了一系列有效的PfSUB1抑制剂的开发。结合简单的合成方法，深入的结构活性研究和计算机模拟研究，我们确定了迄今为止已知的最有效的抑制剂，其特征在于与原型肽相比，具有更高的酶抑制能力和降低的肽特性。
• Total chemical synthesis of human thyroid-stimulating hormone (hTSH) β-subunit: Application of arginine-tagged acetamidomethyl (AcmR) protecting groups
  作者：John A. Brailsford、Jennifer L. Stockdill、Abram J. Axelrod、Michael T. Peterson、Paul A. Vadola、Eric V. Johnston、Samuel J. Danishefsky

  DOI：10.1016/j.tet.2018.02.067

  日期：2018.4

  synthesized as a single glycoform bearing a chitobiose disaccharide at the native glycosylation site. Key to the successful completion of this synthesis was the introduction of an arginine-tagged acetamidomethyl group, which served to greatly facilitate handling of a glycopeptide fragment with poor aqueous solubility. This general solution to the challenge of working with intractable peptides is expected

  人促甲状腺激素 (hTSH) 的 β 亚基已被合成为在天然糖基化位点带有壳二糖的单一糖型。成功完成该合成的关键是引入精氨酸标记的乙酰氨基甲基，这极大地促进了水溶性差的糖肽片段的处理。这种应对棘手肽挑战的通用解决方案预计将在蛋白质合成中得到广泛应用。