nicotinate D-ribonucleoside | 4013-06-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: nicotinate D-ribonucleoside
• 英文别名: nicotinamide acid riboside；nicotinic acid riboside；nicotinate riboside；NAR；D-ribosylnicotinic acid；1-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]pyridin-1-ium-3-carboxylic acid
• CAS: 4013-06-3
• 化学式: C₁₁H₁₄NO₆
• 分子量: 256.235
• InChiKey: PUEDDPCUCPRQNY-ZYUZMQFOSA-O

物化性质

• 物理描述：
  Solid

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  nicotinate D-ribonucleoside 在 human CD₁₅₇ 、 水 作用下， 以 aq. phosphate buffer 为溶剂， 生成 烟酸
  参考文献：
  名称：

  A pre-steady state and steady state kinetic analysis of the N-ribosyl hydrolase activity of hCD157

  摘要：

  hCD157 catalyzes the hydrolysis of nicotinamide riboside (NR) and nicotinic acid riboside (NAR). The release of nicotinamide or nicotinic acid from NR or NAR was confirmed by spectrophotometric, HPLC and NMR analyses. hCD157 is inactivated by a mechanism-based inhibitor, 2'-deoxy-2'-fluoro-nicotin-amide arabinoside (fNR). Modification of the enzyme during the catalytic cycle by NR, NAR, or fNR increased the intrinsic protein fluorescence by approximately 50%. Pre-steady state and steady state data were used to derive a minimal kinetic scheme for the hydrolysis of NR. After initial complex formation a reversible step (360 and 30 s(-1)) is followed by a slow irreversible step (0.1 s(-1)) that defined the rate limiting step, or k(cat). The calculated K-Mapp value for NR in the hydrolytic reaction is 6 nM. The values of the kinetic constants suggest that one biological function of cell-surface hCD157 is to bind and slowly hydrolyze NR, possibly converting it to a ligand-activated receptor. Differences in substrate preference between hCD157 and hCD38 were rationalized through a comparison of the crystal structures of the two proteins. This comparison identified several residues in hCD157 (F108 and F173) that can potentially hinder the binding of dinucleotide substrates (NAD(+)). (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.abb.2014.09.008
• 作为产物：
  描述：

  2,3-吡啶二甲酸 、 磷酸核糖焦磷酸 在 quinolinic acid phosphoribosyl transferase homologue PyrZ 、 magnesium chloride 作用下， 以 aq. buffer 为溶剂， 生成 nicotinate D-ribonucleoside
  参考文献：
  名称：

  双功能 NadC 同系物 PyrZ 催化吡哆霉素生物合成中的烟酸形成

  摘要：

  Pyridomycin 是一种有效的抗分枝杆菌天然产物，通过特异性抑制 InhA，InhA 是一种临床验证的抗结核药物发现靶标。吡啶霉素的吡啶基部分通过占据烟酰胺腺嘌呤二核苷酸 (NADH) 辅助因子结合位点的还原形式，在抑制 InhA 中发挥重要作用。在此，我们对 PyrZ 进行生化表征，它是一种多功能 NadC 同系物，可催化烟酸单核苷酸 (NAMN) 的连续形成、去磷酸化和核糖水解，生成烟酸 (NA)，烟酸 (NA) 是吡啶霉素吡啶基部分的生物合成前体。与底物喹啉酸 (QA) 和最终产物 NA 复合的 PyrZ 的晶体结构揭示了在 K184 和 QA 的 C3-羧基之间形成的特定盐桥。这种相互作用将 QA 定位为接受磷酸核糖基团以生成 NAMN，将 NAMN 保留在活性位点内，并介导其易位至亲核试剂 D296 以进行去磷酸化。结合动力学和热力学分析与定点诱变，提出了 PyrZ 去磷酸

  DOI：

  10.1021/acschembio.2c00773

文献信息

• [EN] LACTONE INTERMEDIATES OF NICOTINAMIDE RIBOSIDE AND NICOTINATE RIBOSIDE<br/>[FR] INTERMÉDIAIRES DE LACTONE DE NICOTINAMIDE RIBOSIDE ET DE NICOTINATE RIBOSIDE
  申请人：UNIV BELFAST

  公开号：WO2018033639A1

  公开（公告）日：2018-02-22

  The present invention is directed to lactones of the following structural formula for use as precursors of NAD, and their use as nutritional supplements.

  本发明涉及以下结构式的内酯，用作NAD的前体，并且它们的用途作为营养补充剂。
• NICOTINIC ACID RIBOSIDE OR NICOTINAMIDE RIBOSIDE COMPOSITIONS, REDUCED DERIVATIVES THEREOF, AND THE USE THEREOF TO ENHANCE SKIN PERMEATION IN TREATING SKIN CONDITIONS
  申请人：ChromaDex Inc.

  公开号：US20160272668A1

  公开（公告）日：2016-09-22

  Derivatives of nicotinic acid riboside (NAR), nicotinamide riboside (NR), and reduced NAR and NR, including 1-(2′,3′,5′-triacetyl-beta-D-ribofuranosyl)-1,4-dihydronicotinic acid (4a), and compositions containing the same and/or reduced derivative forms of nicotinamide riboside including 1-(2′,3′,5′-triacetyl-beta-D-ribofuranosyl)-1,4-nicotinamide (2), are provided for use in the care of treatment of skin and skin conditions. In some embodiments, the invention relates to pharmaceutical compositions and cosmetic compositions containing one or more NR, NAR, NRH, or NARH derivatives, or prodrugs or salts thereof. In further embodiments, the invention relates to methods of using one or more NR, NAR, NRH, or NARH derivatives, or prodrugs, solvates, or salts thereof, to promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival and overall cell and tissue health.

  本发明提供了烟酸核苷酸衍生物（NAR）、烟酰胺核苷酸（NR）和还原的NAR和NR的衍生物，包括1-（2′，3′，5′-三乙酰基-β-D-核糖呋喃基）-1,4-二氢烟酸（4a），以及含有这些衍生物和/或还原的烟酰胺核苷酸衍生物的组合物，用于护理和治疗皮肤和皮肤状况。在某些实施例中，本发明涉及含有一个或多个NR、NAR、NRH或NARH衍生物、前药或其盐的药物组合物和化妆品组合物。在进一步的实施例中，本发明涉及使用一个或多个NR、NAR、NRH或NARH衍生物、前药、溶剂化合物或其盐的方法，以促进细胞和组织中尼古酰胺腺嘌呤二核苷酸（NAD+）的细胞内水平的增加，从而改善细胞和组织的存活和整体健康。
• EFFICIENT AND SCALABLE SYNTHESES OF NICOTINOYL RIBOSIDES AND REDUCED NICOTINOYL RIBOSIDES, MODIFIED DERIVATIVES THEREOF, PHOSPHORYLATED ANALOGS THEREOF, ADENYLYL DINUCLEOTIDE CONJUGATES THEREOF, AND NOVEL CRYSTALLINE FORMS THEREOF
  申请人：The Queen's University of Belfast

  公开号：US20180134743A1

  公开（公告）日：2018-05-17

  The present disclosure provides methods of making nicotinoyl riboside compounds or derivatives of formula (I): wherein X − , Z 1 , Z 2 , n, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8 are described herein, reduced analogs thereof, modified derivatives thereof, phosphorylated analogs thereof, and adenylyl dinucleotide conjugates thereof, or salts, solvates, or prodrugs thereof; and novel crystalline forms thereof.

  本公开提供制备式(I)的烟酰胺核苷化合物或其衍生物的方法：其中X−、Z1、Z2、n、R1、R2、R3、R4、R5、R6、R7和R8如本文所述，其还包括还原的类似物、修饰的衍生物、磷酸化的类似物和腺苷酸二核苷酸共轭物，或其盐、溶剂化合物或前药；以及其新的晶体形式。
• Efficient and scalable syntheses of nicotinoyl ribosides and reduced nicotinoyl ribosides, modified derivatives thereof, phosphorylated analogs thereof, adenylyl dinucleotide conjugates thereof, and novel crystalline forms thereof
  申请人：The Queen's University of Belfast

  公开号：US10689411B2

  公开（公告）日：2020-06-23

  The present disclosure provides methods of making nicotinoyl riboside compounds or derivatives of formula (I): wherein X−, Z1, Z2, n, R1, R2, R3, R4, R5, R6, R7, and R8 are described herein, reduced analogs thereof, modified derivatives thereof, phosphorylated analogs thereof, and adenylyl dinucleotide conjugates thereof, or salts, solvates, or prodrugs thereof; and novel crystalline forms thereof.

  本公开提供了制造式（I）烟酰核糖甙化合物或衍生物的方法： 其中X-、Z1、Z2、n、R1、R2、R3、R4、R5、R6、R7和R8如本文所述，其还原类似物、其修饰衍生物、其磷酸化类似物和其腺苷二核苷酸共轭物，或其盐、溶液或原药；以及其新型结晶形式。
• Use of nicotinamide riboside, nicotinic acid riboside, and nicotinamide mononucleotide, reduced nicotinyl compounds, and nicotinoyl compound derivatives in infant formula for healthy development
  申请人：ChromaDex, Inc.

  公开号：US10857172B2

  公开（公告）日：2020-12-08

  Methods for delivering at least one compound selected from nicotinamide riboside (NR), nicotinic acid riboside (NAR), and nicotinamide mononucleotide (NMN), derivatives thereof, or salts thereof, in combination with at least one of thiamine (vitamin B1), riboflavin (vitamin B2), niacin (vitamin B3), and pyridoxine (vitamin B6), to an infant human subject in need of said compound or compounds are provided.

  提供了将至少一种选自烟酰胺核糖苷（NR）、烟酸核糖苷（NAR）和烟酰胺单核苷酸（NMN）的化合物、其衍生物或其盐与硫胺素（维生素 B1）、核黄素（维生素 B2）、烟酸（维生素 B3）和吡哆醇（维生素 B6）中的至少一种结合起来，输送给需要所述化合物的婴儿人体的方法。