14426-53-0Relevant academic research and scientific papers
Synthesis and ability of new ligands for G protein-coupled receptors 17 (GPR17)
Zhuo, Tongyou,Zhou, Shengxue,Zhang, Wei,Lambertucci, Catia,Volpini, Rosaria
, p. 953 - 959 (2017/03/20)
Background: GPR17 is believed to be a novel target for the development of new therapeutic approaches to human stroke and multiple sclerosis. Hence, the selection of GPR17 ligands may be a potent way to reduce the progression of ischemic damage. Material/Methods: New potential ligands for GPR17, mono-, di-, and triphosphate adenosine nucleotides substituted at N6-position with a methyl and a cyclopentyl group were synthesized. The ability of new ligands to bind GPR17 was evaluated using frontal affinity chromatography-mass spectrometry (FAC-MS) method. Cangrelor, MRS2179, and uridine diphosphate were selected as the reference compounds. Results: The new triphosphate derivatives 9 and 10 were considered as the new GPR17 ligands. The compound 10 was eluted with breakthrough time (bt) between cangrelor and MRS 2179 (compound 10, bt=12.25; cangrelor, bt=24.55, and MRS 2179, bt=7.10), while the breakthrough volume of compound 9 was similar to that of MRS 2179 (compound 9, bt=7.53 and MRS 2179, bt=7.10). Conclusions: N6-cyclopentyATP 10 is medium-high affinity ligand of GPR17, while the corresponding N6-methyl derivative 9 is a medium affinity ligand similar to MRS 2179. Hence, the new N6-cyclopentylATP 10 might be a good candidate for the pharmacological characterization of GPR17.
Aeromonas hydrophila strains as biocatalysts for transglycosylation
Nbile, Matas,Terreni, Marco,Lewkowicz, Elizabeth,Iribarren, Adolfo M.
experimental part, p. 395 - 402 (2011/10/08)
Microbial transglycosylation is useful as a green alternative in the preparation of purine nucleosides and analogues, especially for those that display pharmacological activities. In a search for new transglycosylation biocatalysts, two Aeromonas hydrophila strains were selected. The substrate specificity of both micro-organisms was studied and, as a result, several nucleoside analogues have been prepared. Among them, ribavirin, a broad spectrum antiviral, and the well-known anti HIV didanosine, were prepared, in 77 and 62% yield using A. hydrophila CECT 4226 and A. hydrophila CECT 4221, respectively. In order to scale-up the processes, the reaction conditions, product purification and biocatalyst preparation were analyzed and optimized.
Nucleic acid related compounds. 116. Nonaqueous diazotization of aminopurine nucleosides. Mechanistic considerations and efficient procedures with tert-butyl nitrite or sodium nitrite
Francom, Paula,Janeba, Zlatko,Shibuya, Susumu,Robins, Morris J.
, p. 6788 - 6796 (2007/10/03)
Nonaqueous diazotization-dediazoniation of two types of aminopurine nucleoside derivatives has been investigated. Treatment of 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2-amino-6-chloropurine (1) with SbCl3/CH2Cl2 was examined with benzyltriethylammonium (BTEA) chloride as a soluble halide source and tert-butyl nitrite (TBN) or sodium nitrite as the diazotization reagent. Optimized yields (>80%) of the 2,6-dichloropurine derivative were obtained with SbCl3. Combinations with SbBr3/CH2Br2 gave the 2-bromo-6-chloropurine product (>60%), and SbI3/CH2I2/THF gave the 2-iodo-6-chloropurine derivative (>45%). Antimony trihalide catalysis was highly beneficial. Mixed combinations (SbX3/CH2X′2; X/X′ = Bt/Cl) gave mixtures of 2-(bromo, chloro, and hydro)-6- chloropurine derivatives that were dependent on reaction conditions. Addition of iodoacetic acid (IAA) resulted in diversion of purine radical species into a 2-iodo-6-chloropurine derivative with commensurate loss of other radical-derived products. This allowed evaluation of the efficiency of SbX3-promoted cation-derived dediazoniations relative to radical-derived reactions. Efficient conversions of adenosine, 2′-deoxyadenosine, and related adenine nucleosides into 6-halopurine derivatives of current interest were developed with analogous combinations.
