H-Rink amide ChemMatrix resin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂环丁烷
• 英文名称: H-Rink amide ChemMatrix resin
• 英文别名: 3-(Dimethylamino)butyl 3,3-difluoroazetidine-1-carboxylate;oxalic acid
• 化学式: C₁₈H₂₁N₂O₄Pol
• 分子量: 326.29
• InChiKey: SXIJPPSVASDXRW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.57
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  H-Rink amide ChemMatrix resin 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-1,2-bis(3,5-dimethoxyphenyl)-2-hydroxyethanone
  参考文献：
  名称：

  Synthesis and evaluation of phosphopeptides containing iminodiacetate groups as binding ligands of the Src SH2 domain

  摘要：

  Phosphopeptide pTyr-Glu-Glu-Ile (pYEEI) has been introduced as an optimal Src SH2 domain ligand. Peptides, Ac-K(IDA)pYEEIEK(IDA) (1), Ac-KpYEEIEK (2), Ac-K(IDA) pYEEIEK (3), and Ac-KpYEEIEK(IDA) (4), containing 0-2 iminodiacetate (IDA) groups at the N- and C-terminal lysine residues were synthesized and evaluated as the Src SH2 domain binding ligands. Fluorescence polarization assays showed that peptide 1 had a higher binding affinity (K-d = 0.6 mu M) to the Src SH2 domain when compared with Ac-pYEEI (K-d = 1.7 mu M), an optimal Src SH2 domain ligand, and peptides 2-4 (K-d = 2.9-52.7 mu M). The binding affinity of peptide 1 to the SH2 domain was reduced by more than 2-fold (K-d = 1.6 mu M) upon addition of Ni2+ (300 mu M), possibly due to modest structural effect of Ni2+ on the protein as shown by circular dichroism experimental results. The binding affinity of 1 was restored in the presence of EDTA (300 mu M) (K-d = 0.79 mu M). These studies suggest that peptides containing IDA groups may be used for designing novel SH2 domain binding ligands. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2009.05.003
• 作为产物：
  描述：

  (R)-1,2-bis(3,5-dimethoxyphenyl)-2-hydroxyethanone 在 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 H-Rink amide ChemMatrix resin
  参考文献：
  名称：

  Synthesis and evaluation of phosphopeptides containing iminodiacetate groups as binding ligands of the Src SH2 domain

  摘要：

  Phosphopeptide pTyr-Glu-Glu-Ile (pYEEI) has been introduced as an optimal Src SH2 domain ligand. Peptides, Ac-K(IDA)pYEEIEK(IDA) (1), Ac-KpYEEIEK (2), Ac-K(IDA) pYEEIEK (3), and Ac-KpYEEIEK(IDA) (4), containing 0-2 iminodiacetate (IDA) groups at the N- and C-terminal lysine residues were synthesized and evaluated as the Src SH2 domain binding ligands. Fluorescence polarization assays showed that peptide 1 had a higher binding affinity (K-d = 0.6 mu M) to the Src SH2 domain when compared with Ac-pYEEI (K-d = 1.7 mu M), an optimal Src SH2 domain ligand, and peptides 2-4 (K-d = 2.9-52.7 mu M). The binding affinity of peptide 1 to the SH2 domain was reduced by more than 2-fold (K-d = 1.6 mu M) upon addition of Ni2+ (300 mu M), possibly due to modest structural effect of Ni2+ on the protein as shown by circular dichroism experimental results. The binding affinity of 1 was restored in the presence of EDTA (300 mu M) (K-d = 0.79 mu M). These studies suggest that peptides containing IDA groups may be used for designing novel SH2 domain binding ligands. (C) 2009 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2009.05.003
• 作为试剂：
  描述：

  Fmoc-L-亮氨酸 、 FMOC-beta-丙氨酸 、 Fmoc-L-苯丙氨酸 、 Fluorescein isothiocyanate 、 N-alpha-芴甲氧羰基-N-epsilon-叔丁氧羰基-L-赖氨酸 、 Fmoc-S-三苯甲基-L-半胱氨酸 、 Fmoc-L-色氨酸(Boc)-OH 、 Fmoc-N'-乙酰基-L-赖氨酸 在 H-Rink amide ChemMatrix resin 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 哌啶 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成
  参考文献：
  名称：

  转录共激活因子 CBP 环肽调节剂的合理设计：一类新的 p53 抑制剂

  摘要：

  CREB ​​结合蛋白 (CBP) 是一种人类转录共激活因子，由几个保守的功能模块组成，可与不同的转录因子相互作用，包括核受体、CREB ​​和 STAT 蛋白。尽管 CBP 在转录调控中很重要，但关于其特定域在 CBP 功能中的作用的许多问题仍未得到解答。因此，开发能够选择性调节 CBP 单个结构域的小分子对于揭示其突出的活性具有宝贵的帮助。在这里，我们报告了构象限制肽作为 CBP 乙酰赖氨酸结合溴结构域 (BRD) 的新型调节剂的设计、合成和生物学评估。利用目标结构引导和计算机辅助的合理设计方法，我们开发了一系列对 CBP BRD 亲和力显着高于其生物配体的环肽，包括赖氨酸乙酰化组蛋白和肿瘤抑制因子 p53。该系列中最好的环肽的 K(d) 为 8.0 μM，与线性赖氨酸 382 乙酰化 p53 肽相比，亲和力提高了 24 倍。这种先导肽对 CBP BRD 的选择性高于来自其他转录蛋白的

  DOI：

  10.1021/ja107761h

文献信息

• 4-Chloro-2-Fluoro-5-Nitrobenzoic Acid as a Possible Building Block for Solid-phase Synthesis of Various Heterocyclic Scaffolds
  作者：Soňa Křupková、Petr Funk、Miroslav Soural、Jan Hlaváč

  DOI：10.1021/co300109h

  日期：2013.1.14

  4-Chloro-2-fluoro-5-nitrobenzoic acid is a commercially available multireactive building block that can serve as a starting material in heterocyclic oriented synthesis (HOS) leading to various condensed nitrogenous cycles. This work describes its ability for the preparation of substituted nitrogenous heterocycles having 5–7-membered cycles via polymer-supported o-phenylendiamines. Immobilization of

  4-氯-2-氟-5-硝基苯甲酸是一种可在市场上买到的多反应性结构单元，可以用作杂环定向合成（HOS）的起始原料，从而导致各种稠密的含氮循环。这项工作描述了其通过聚合物负载的邻位环制备具有5–7元环的取代的含氮杂环的能力。-苯二胺。将该化合物固定在Rink树脂上，接着进行进一步的氯取代，还原硝基并适当环化，得到苯并咪唑，苯并三唑，喹喔啉酮，苯并二氮杂二酮和琥珀酰亚胺。所开发的方法适用于各种文库的合成，包括上述类型的杂环，这些杂环在当前的药物发现中具有重要意义。在本文中，我们还报告了这些方法的局限性以及制备8员苯并重氮电影周期的尝试失败。
• Side-Selective Solid-Phase Metallaphotoredox <i>N</i>_(in)-Arylation of Peptides
  作者：José A. C. Delgado、Ya-Ming Tian、Michela Marcon、Burkhard König、Márcio W. Paixão

  DOI：10.1021/jacs.3c10792

  日期：2023.12.6

  in solid-phase peptide synthesis for the on-resin orthogonal N-arylation of relevant tryptophan-containing peptides. The protocol allows the chemoselective introduction of a new C(sp2)–N bond at the N(in) of tryptophan in biologically active protected peptide sequences in the presence of native redox-sensitive side chains. The fusion of metallaphotocatalysis with solid-phase peptide synthesis opens

  通过选择性修饰内源氨基酸侧链来实现肽的合成后多样化，使得肽药物发现取得了重大进展，同时扩大了生物和医学化学空间。然而，当前的工具一直集中在反应性极性和可电​​离侧链的修饰上，而芳香系统（例如色氨酸的N （in） ）的修饰一直是一个长期存在的挑战。在这里，我们在固相肽合成中引入金属光催化，用于相关含色氨酸肽的树脂上正交N -芳基化。该方案允许在天然氧化还原敏感侧链存在的情况下，在生物活性受保护肽序列中的色氨酸N (in)处化学选择性地引入新的 C(sp 2 )–N 键。金属光催化与固相肽合成的融合为天然氨基酸侧链多样化开辟了新的前景。
• Eleven Amino Acid Glucagon-like Peptide-1 Receptor Agonists with Antidiabetic Activity
  作者：Claudio Mapelli、Sesha I. Natarajan、Jean-Philippe Meyer、Margarita M. Bastos、Michael S. Bernatowicz、Ving G. Lee、Jelka Pluscec、Douglas J. Riexinger、Ellen S. Sieber-McMaster、Keith L. Constantine、Constance A. Smith-Monroy、Rajasree Golla、Zhengping Ma、Daniel A. Longhi、Dan Shi、Li Xin、Joseph R. Taylor、Barry Koplowitz、Cecilia L. Chi、Ashish Khanna、Gordon W. Robinson、Ramakrishna Seethala、Ildiko A. Antal-Zimanyi、Robert H. Stoffel、Songping Han、Jean M. Whaley、Christine S. Huang、John Krupinski、William R. Ewing

  DOI：10.1021/jm900752a

  日期：2009.12.10

  Glucagon-like peptide 1 (GLP-1) is a 30 or 31 amino acid peptide hormone that contributes to the physiological regulation of glucose homeostasis and food intake. Herein, we report the discovery of a novel class of 11 amino acid GLP-1 receptor agonists. These peptides consist of a structurally optimized 9-mer, which is closely related to the N-terminal 9 amino acids of GLP-1, linked to a substituted C-terminal biphenylalanine (BIP) dipeptide. SAR studies resulted in 11-mer GLP-1R agonists with similar in vitro potency to the native 30-mer. Peptides 21 and 22 acutely reduced plasma glucose excursions and increased plasma insulin concentrations in a Mouse model of diabetes. These peptides also showed sustained exposures over several hours in mouse and dog models. The described 11-mer GLP-1 receptor agonists represent a new tool in further understanding GLP-1 receptor pharmacology that may lead to novel antidiabetic agents.
• Novel Acetylcholine and Carbamoylcholine Analogues: Development of a Functionally Selective α₄β₂ Nicotinic Acetylcholine Receptor Agonist
  作者：Camilla P. Hansen、Anders A. Jensen、Jeppe K. Christensen、Thomas Balle、Tommy Liljefors、Bente Frølund

  DOI：10.1021/jm701625v

  日期：2008.12.11

  A series of carbamoylcholine and acetylcholine analogues were synthesized and characterized pharmacologically at neuronal nicotinic acetylcholine receptors (nAChRs). Several of the compounds displayed low nanomolar binding affinities to the alpha(4)beta(2) nAChR and pronounced selectivity for this subtype over alpha(3)beta(4), alpha(4)beta(4), and alpha(7) nAChRs. The high nAChR activity of carbamoylcholine analogue 5d was found to reside in its R-enantiomer, a characteristic most likely true for all other compounds in the series. Interestingly, the pronounced alpha(4)beta(2) selectivities exhibited by some of the compounds in the binding assays translated into functional selectivity. Compound 5a was a fairly potent partial alpha(4)beta(2) nAChR agonist with negligible activities at the alpha(3)beta(4) and alpha(7) subtypes, thus being one of the few truly functionally selective alpha(4)beta(2) nAChR agonists published to date. Ligand-protein docking experiments using homology models of the amino-terminal domains of alpha(4)beta(2) and alpha(3)beta(4) nAChRs identified residues Val 111(beta(2))/Ile 113(beta(4)), Phe 119(beta(2))/Gln 121(beta(4)), and Thr155(alpha(4))/Ser 150(alpha(3)) as possible key determinants of the alpha(4)beta(2)/alpha(3)beta(4)-selectivity displayed by the analogues. 4
• Amino Acid–Viologen Hybrids: Synthesis, Cucurbituril Host–Guest Chemistry, and Implementation on the Production of Peptides
  作者：Liliana Barravecchia、Iago Neira、Elena Pazos、Carlos Peinador、Marcos D. García

  DOI：10.1021/acs.joc.1c02040

  日期：2022.1.7