H-Arg(Pbf)-OMe*HCl

• 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: H-Arg(Pbf)-OMe*HCl
• 英文别名: Nomega-(2,2,4,6,7-Pentamethyl-3H-1-benzofuran-5-yl)sulfonyl-L-arginine methyl ester HCl；methyl 2-amino-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]pentanoate;hydrochloride
• 化学式: C₂₀H₃₂N₄O₅S*ClH
• 分子量: 477.025
• InChiKey: YPQBZJQUKCGWKC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.62
• 重原子数：
  31
• 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：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  H-Arg(Pbf)-OMe*HCl 在 三异丙基硅烷 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 5.5h， 生成 1-Phenyl-4-(3-guanidinpropyl)-hydantoin
  参考文献：
  名称：

  Identification of Multiple Structurally Distinct, Nonpeptidic Small Molecule Inhibitors of Protein Arginine Deiminase 3 Using a Substrate-Based Fragment Method

  摘要：

  The protein arginine deiminases (PADs) are a family of enzymes that catalyze the post-translational hydrolytic deimination of arginine residues. Four different enzymologically active PAD subtypes have been characterized and exhibit tissue-specific expression and association with a number of different diseases. In this Article we describe the development of an approach for the reliable discovery of low molecular weight, nonpeptidic fragment substrates of the PADs that then can be optimized and converted to mechanism-based irreversible PAD inhibitors. The approach is demonstrated by the development of potent and selective inhibitors of PAD3, a PAD subtype implicated in the neurodegenerative response to spinal cord injury. Multiple structurally distinct inhibitors were identified with the most potent inhibitors having >10,000 min(-1) M-1 k(inact)/K-I values and >= 10-fold selectivity for PAD3 over PADs 1, 2, and 4.

  DOI：

  10.1021/jacs.5b00095

文献信息

• Deaminative Arylation of Amino Acid-derived Pyridinium Salts
  作者：Megan E. Hoerrner、Kristen M. Baker、Corey H. Basch、Earl M. Bampo、Mary P. Watson

  DOI：10.1021/acs.orglett.9b02643

  日期：2019.9.20

  A Suzuki–Miyaura cross-coupling of α-pyridinium esters and arylboroxines has been developed. Combined with formation of the pyridinium salts from amino acid derivatives, this method enables amino acid derivatives to be efficiently transformed into α-aryl esters and amides. Under the mild conditions, broad functional group tolerance on both the amino acid derivatives and the arylboroxine are observed

  α-吡啶鎓酯和芳基环硼氧烷的铃木-宫浦交叉偶联已被开发出来。结合氨基酸衍生物形成吡啶鎓盐，该方法能够将氨基酸衍生物有效转化为α-芳基酯和酰胺。在温和条件下，观察到氨基酸衍生物和芳基环硼氧烷具有广泛的官能团耐受性，包括质子官能团。机理研究支持烷基自由基中间体，类似于烷基吡啶鎓盐的其他交叉偶联。
• 一种光控释放ONOO^－的化合物及其制备方法和应用
  申请人：山西大学

  公开号：CN117486828A

  公开（公告）日：2024-02-02

  本发明属于生物医药领域，具体涉及一种光控释放ONOO－的化合物及其制备方法和应用。本发明提供的ONOO‑供体由二苯吩噻嗪类似物和精氨酸共价连接而成，其较强的共轭效应使得其有极强的光响应能力，该聚合物具有近红外光发射，同时具有优异的活性氧、活性氮产生能力。当L6在660nm激光照射下会产生超氧阴离子和单线态氧，单线态氧氧化精氨酸的胍基产生NO，·O2‑和NO生成过氧亚硝酸盐(ONOO‑)，达到对高效杀伤肿瘤细胞的目的。因而该化合物是一种潜在高效杀伤肿瘤的光敏剂。这种杀伤方式与普通光敏剂相比具有更强的氧化和硝化损伤细胞能力，且开发周期相对于其它光敏药物短，因而可以在临床治疗当中具有很大的潜在应用价值。
• Identification of Multiple Structurally Distinct, Nonpeptidic Small Molecule Inhibitors of Protein Arginine Deiminase 3 Using a Substrate-Based Fragment Method
  作者：Haya Jamali、Hasan A. Khan、Joseph R. Stringer、Somenath Chowdhury、Jonathan A. Ellman

  DOI：10.1021/jacs.5b00095

  日期：2015.3.18

  The protein arginine deiminases (PADs) are a family of enzymes that catalyze the post-translational hydrolytic deimination of arginine residues. Four different enzymologically active PAD subtypes have been characterized and exhibit tissue-specific expression and association with a number of different diseases. In this Article we describe the development of an approach for the reliable discovery of low molecular weight, nonpeptidic fragment substrates of the PADs that then can be optimized and converted to mechanism-based irreversible PAD inhibitors. The approach is demonstrated by the development of potent and selective inhibitors of PAD3, a PAD subtype implicated in the neurodegenerative response to spinal cord injury. Multiple structurally distinct inhibitors were identified with the most potent inhibitors having >10,000 min(-1) M-1 k(inact)/K-I values and >= 10-fold selectivity for PAD3 over PADs 1, 2, and 4.