3-carbamoyl-1-[O⁵-(1,2-dihydroxy-2-inosin-5'-yloxy-diphosphoryl)-β-D-ribofuranosyl]-pyridinium betaine | 1851-07-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - （5'->5'）-二核苷酸
• 英文名称: 3-carbamoyl-1-[O⁵-(1,2-dihydroxy-2-inosin-5'-yloxy-diphosphoryl)-β-D-ribofuranosyl]-pyridinium betaine
• 英文别名: 3-Carbamoyl-1-[O⁵-(1,2-dihydroxy-2-inosin-5'-yloxy-diphosphoryl)-β-D-ribofuranosyl]-pyridinium-betain；Nicotinamide purin-6-ol-dinucleotide；[(2R,3S,4R,5R)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl [[(2R,3S,4R,5R)-3,4-dihydroxy-5-(6-oxo-1H-purin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphate
• CAS: 1851-07-6
• 化学式: C₂₁H₂₆N₆O₁₅P₂
• 分子量: 664.416
• InChiKey: DGVSIBCCYUVRNA-NNYOXOHSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -6.3
• 重原子数：
  44
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  311
• 氢给体数：
  7
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  3-carbamoyl-1-[O⁵-(1,2-dihydroxy-2-inosin-5'-yloxy-diphosphoryl)-β-D-ribofuranosyl]-pyridinium betaine 在 sodium dithionite 、 水 、 potassium hydrogencarbonate 作用下， 生成 Hydronicotinamidhypoxanthindinucleotid
  参考文献：
  名称：

  van Eys et al., Journal of Biological Chemistry, 1958, vol. 231, p. 571,572

  摘要：

  DOI：
• 作为产物：
  描述：

  nicotinamide adenine dinucleotide 在 adenosine( phosphate)-daminase 作用下， 生成 3-carbamoyl-1-[O⁵-(1,2-dihydroxy-2-inosin-5'-yloxy-diphosphoryl)-β-D-ribofuranosyl]-pyridinium betaine
  参考文献：
  名称：

  Kaplan et al., Journal of Biological Chemistry, 1952, vol. 194, p. 579,581,582

  摘要：

  DOI：

文献信息

• Structure–Activity Relationship of Adenosine 5′-diphosphoribose at the Transient Receptor Potential Melastatin 2 (TRPM2) Channel: Rational Design of Antagonists
  作者：Christelle Moreau、Tanja Kirchberger、Joanna M. Swarbrick、Stephen J. Bartlett、Ralf Fliegert、Timur Yorgan、Andreas Bauche、Angelika Harneit、Andreas H. Guse、Barry V. L. Potter

  DOI：10.1021/jm401497a

  日期：2013.12.27

  Adenosine S'-diphosphoribose (ADPR) activates TRPM2, a Ca2+, Na+, and K+ permeable cation channel. Activation is induced by ADPR binding to the cytosolic C-terminal NudT9-homology domain. To generate the first structure activity relationship, systematically modified ADPR analogues were designed, synthesized, and evaluated as antagonists using patch-clamp experiments in HEK293 cells overexpressing human TRPM2. Compounds with a purine C8 substituent show antagonist activity, and an 8-phenyl substitution (8-Ph-ADPR, 5) is very effective. Modification of the terminal ribose results in a weak antagonist, whereas its removal abolishes activity. An antagonist based upon a hybrid structure, 8-phenyl-2'-deoxy-ADPR (86, IC50 = 3 mu M), is more potent than 8-Ph-ADPR (5). Initial bioisosteric replacement of the pyrophosphate linkage abolishes activity, but replacement of the pyrophosphate and the terminal ribose by a sulfarnate-based group leads to a weak antagonist, a lead to more drug-like analogues. 8-Ph-ADPR (5) inhibits Ca2+ signalling and chemotaxis in human neutrophils, illustrating the potential for pharmacological intervention at TRPM2.
• Yamada, Shinji; Gu, Qu-Ming; Sih, Charles J., Journal of the American Chemical Society, 1994, vol. 116, # 23, p. 10787 - 10788
  作者：Yamada, Shinji、Gu, Qu-Ming、Sih, Charles J.

  DOI：——

  日期：——
• Schlenk et al., Chemische Berichte, 1938, vol. 71, p. 1471,1476
  作者：Schlenk et al.

  DOI：——

  日期：——
• Sund et al., 1964, vol. 26, p. 115,135
  作者：Sund et al.

  DOI：——

  日期：——
• Novel enzymatic cyclizations of pyridine nucleotide analogs: Cyclic-GDP-ribose and cyclic-HDP-ribose
  作者：Fang-Jie Zhang、Charles J. Sih

  DOI：10.1016/0040-4039(95)02004-9

  日期：1995.12

  The cyclase of Aplysia californica catalyzed an alternative mode of cyclization of nicotinamide guanine dinucleotide (NGD) and nicotinamide hypoxanthine dinucleotide (NHD) to form cyclic-GDP-ribose (cGDPR) and cyclic-HDP-ribose (cHDPR) respectively. In these cyclic nucleotides, the newly formed glycosyl bonds are attached onto the N-7 nitrogen of the purine rings instead of the N-1 nitrogen as in cyclic ADP-ribose (cADPR).