98855-71-1Relevant articles and documents
A Simple and Convenient Method for the Synthesis of 1-(2-Deoxy-2-fuoro-β-D-arabinofuranosyl)-5-iodocytosine
Liu, Rong,Wang, Yongsheng,Peng, Weien,Kong, Jianping
, p. 521 - 524 (2021/02/02)
1-(2-Deoxy-2-fluoro-β-D-arabinofuranosyl)-5-iodocytosine (FIAC) is a pyrimidine nucleoside analog with activity against various herpes viruses. In this study, FIAC was conveniently synthesized by a substitution reaction between ((2R,3S,4S)-3-(benzoyloxy)-
A green synthetic clofarabine pharmaceutical intermediates (by machine translation)
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Paragraph 0011; 0012; 0013; 0014; 0015; 0016; 0017, (2019/02/25)
The invention relates to a green synthetic clofarabine medical intermediates, in particular comprises the following steps: The formula II compound is dissolved in the organic solvent, under ice bath by adding 40% of the hydrobromic, tetrabutyl ammonium fluoride, stirring for 3 hours, adding triethylamine three [...], continuing to stir 2 - 3 hours, [...] I compound. (by machine translation)
Revealing CD38 cellular localization using a cell permeable, mechanism-based fluorescent small-molecule probe
Shrimp, Jonathan H.,Hu, Jing,Dong, Min,Wang, Brian S.,Macdonald, Robert,Jiang, Hong,Hao, Quan,Yen, Andrew,Lin, Hening
supporting information, p. 5656 - 5663 (2014/05/06)
Nicotinamide adenine dinucleotide (NAD) is increasingly recognized as an important signaling molecule that affects numerous biological pathways. Thus, enzymes that metabolize NAD can have important biological functions. One NAD-metabolizing enzyme in mammals is CD38, a type II transmembrane protein that converts NAD primarily to adenosine diphosphate ribose (ADPR) and a small amount of cyclic adenosine diphosphate ribose (cADPR). Localization of CD38 was originally thought to be only on the plasma membrane, but later reports showed either significant or solely, intracellular CD38. With the efficient NAD-hydrolysis activity, the intracellular CD38 may lead to depletion of cellular NAD, thus producing harmful effects. Therefore, the intracellular localization of CD38 needs to be carefully validated. Here, we report the synthesis and application of a cell permeable, fluorescent small molecule (SR101-F-araNMN) that can covalently label enzymatically active CD38 with minimal perturbation of live cells. Using this fluorescent probe, we revealed that CD38 is predominately on the plasma membrane of Raji and retinoic acid (RA)-treated HL-60 cells. Additionally, the probe revealed no CD38 expression in K562 cells, which was previously reported to have solely intracellular CD38. The finding that very little intracellular CD38 exists in these cell lines suggests that the major enzymatic function of CD38 is to hydrolyze extracellular rather than intracellular NAD. The fluorescent activity-based probes that we developed allow the localization of CD38 in different cells to be determined, thus enabling a better understanding of the physiological function.
The chemoenzymatic synthesis of clofarabine and related 2′-deoxyfluoroarabinosyl nucleosides: The electronic and stereochemical factors determining substrate recognition by E. coli nucleoside phosphorylases
Fateev, Ilja V.,Antonov, Konstantin V.,Konstantinova, Irina D.,Muravyova, Tatyana I.,Seela, Frank,Esipov, Roman S.,Miroshnikov, Anatoly I.,Mikhailopulo, Igor A.
, p. 1657 - 1669 (2014/10/15)
Two approaches to the synthesis of 2-chloro-9-(2-deoxy-2-fluoro-β-D- arabinofuranosyl)adenine (1, clofarabine) were studied. The first approach consists in the chemical synthesis of 2-deoxy-2-fluoro-α-D- arabinofuranose-1-phosphate (12a, 2FAra-1P) via three step conversion of 1,3,5-tri-O-benzoyl-2-deoxy-2-fluoro-α-D-arabinofuranose (9) into the phosphate 12a without isolation of intermediary products. Condensation of 12a with 2-chloroadenine catalyzed by the recombinant E. coli purine nucleoside phosphorylase (PNP) resulted in the formation of clofarabine in 67% yield. The reaction was also studied with a number of purine bases (2-aminoadenine and hypoxanthine), their analogues (5-aza-7-deazaguanine and 8-aza-7- deazahypoxanthine) and thymine. The results were compared with those of a similar reaction with α-D-arabinofuranose-1-phosphate (13a, Ara-1P). Differences of the reactivity of various substrates were analyzed by ab initio calculations in terms of the electronic structure (natural purines vs analogues) and stereochemical features (2FAra-1P vs Ara-1P) of the studied compounds to determine the substrate recognition by E. coli nucleoside phosphorylases. The second approach starts with the cascade one-pot enzymatic transformation of 2-deoxy-2-fluoro-D-arabinose into the phosphate 12a, followed by its condensation with 2-chloroadenine thereby affording clofarabine in ca. 48% yield in 24 h. The following recombinant E. coli enzymes catalyze the sequential conversion of 2-deoxy-2-fluoro-D-arabinose into the phosphate 12a: ribokinase (2-deoxy-2-fluoro-D-arabinofuranose-5-phosphate), phosphopentomutase (PPN; no 1,6-diphosphates of D-hexoses as co-factors required) (12a), and finally PNP. The substrate activities of D-arabinose, D-ribose and D-xylose in the similar cascade syntheses of the relevant 2-chloroadenine nucleosides were studied and compared with the activities of 2-deoxy-2-fluoro-D-arabinose. As expected, D-ribose exhibited the best substrate activity [90% yield of 2-chloroadenosine (8) in 30 min], D-arabinose reached an equilibrium at a concentration of ca. 1:1 of a starting base and the formed 2-chloro-9-(β-D- arabinofuranosyl) adenine (6) in 45 min, the formation of 2-chloro-9-(β-D- xylofuranosyl)adenine (7) proceeded very slowly attaining ca. 8% yield in 48 h.
Sugar-modified derivatives of cytostatic 7-(het)aryl-7-deazaadenosines: 2′-C-methylribonucleosides, 2′-deoxy-2′- fluoroarabinonucleosides, arabinonucleosides and 2′-deoxyribonucleosides
Naus, Petr,Perlikova, Pavla,Bourderioux, Aurelie,Pohl, Radek,Slavetinska, Lenka,Votruba, Ivan,Bahador, Gina,Birkus, Gabriel,Cihlar, Tomas,Hocek, Michal
, p. 5202 - 5214 (2012/11/07)
A series of novel sugar-modified derivatives of cytostatic 7-hetaryl-7-deazaadenosines (2′-C-methylribonucleosides, 2′-deoxy-2′-fluoroarabinonucleosides, arabinonucleosides and 2′-deoxyribonucleosides) was prepared and screened for biological activity. Th
Sugar-modified derivatives of cytostatic 6-(het)aryl-7-deazapurine nucleosides: 2′-c-methylribonucleosides, arabinonucleosides and 2′-deoxy-2′-fluoroarabinonucleosides
Naus, Petr,Perlikova, Pavla,Pohl, Radek,Hocek, Michal
scheme or table, p. 957 - 988 (2012/06/16)
A series of novel sugar-modified derivatives of cytostatic 6-hetaryl-7-deazapurine ribonucleo-sides: 2′-C-methylribonucleosides, arabinonucleosides and 2′-deoxy-2′-fluoroarabinonucleo-sides bearing an alkyl, aryl and hetaryl group in position 6 were prepared by palladium catalyzed cross-coupling reactions of corresponding (protected) 6-chloro-(7-fluoro)-7-deazapurine nucleosides with (het)arylboronic, hetarylstannanes and trimethylaluminium eventually followed by deprotection. Key intermediate 6-chloro-7-deazapurine 2′-C-methyl-β-D-ribofuranoside was prepared via a stereoselective nucleobase anion glycosylation with toluoyl-protected 1,2-anhydro-2-C-methylribofuranose. The 1,2-anhydro sugar was synthesized in 3 steps starting from readily available 2-C-methylribonolactone. The 6-chloro-7-deazapurine arabinofuranoside intermediate was obtained by epimerization from 3′,5′-protected 6-chloro-7-deazapurine ribofuranoside via 2′-hydroxyl oxidation followed by reduction. None of the prepared compounds showed any considerable cytostatic or antiviral activity.
Discovery of GS-9131: Design, synthesis and optimization of amidate prodrugs of the novel nucleoside phosphonate HIV reverse transcriptase (RT) inhibitor GS-9148
Mackman, Richard L.,Ray, Adrian S.,Hui, Hon C.,Zhang, Lijun,Birkus, Gabriel,Boojamra, Constantine G.,Desai, Manoj C.,Douglas, Janet L.,Gao, Ying,Grant, Deborah,Laflamme, Genevieve,Lin, Kuei-Ying,Markevitch, David Y.,Mishra, Ruchika,McDermott, Martin,Pakdaman, Rowchanak,Petrakovsky, Oleg V.,Vela, Jennifer E.,Cihlar, Tomas
experimental part, p. 3606 - 3617 (2010/08/05)
GS-9148 [(5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl)phosph onic acid] 4 is a novel nucleoside phosphonate HIV-1 reverse transcriptase (RT) inhibitor with a unique resistance profile toward N(t)RTI resistance mutations. To effectively
2′-Fluorosugar analogues of the highly potent anti-varicella-zoster virus bicyclic nucleoside analogue (BCNA) Cf 1743
McGuigan, Christopher,Derudas, Marco,Quintiliani, Maurizio,Andrei, Graciela,Snoeck, Robert,Henson, Geoffrey,Balzarini, Jan
scheme or table, p. 6264 - 6267 (2010/08/20)
We report the preparation of 2′-α-F, 2′-β-F and 2′,2′-difluoro analogues of the leading anti-varicella zoster virus (VZV) pentylphenyl BCNA Cf 1743. VZV thymidine kinase showed the highest phosphorylating capacity for the β-fluoro derivative, that retaine
ANTIVIRAL PHOSPHINATE COMPOUNDS
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Page/Page column 260, (2008/06/13)
A compound of Formula I, Formula II, Formula III, or Formula IV: or a pharmaceutically acceptable salt, solvate, and/or ester thereof, therapeutic compositions containing such compounds, and therapeutic methods that include the administation of such compo
Synthesis and anti-HIV activity of 2′-fluorine modified nucleoside phosphonates: Analogs of GS-9148
Mackman, Richard L.,Lin, Kuei-Ying,Boojamra, Constantine G.,Hui, Hon,Douglas, Janet,Grant, Deborah,Petrakovsky, Oleg,Prasad, Vidya,Ray, Adrian S.,Cihlar, Tomas
, p. 1116 - 1119 (2008/09/19)
Modified purine analogs of GS-9148 [5-(6-amino-purin-9-yl)-4-fluoro-2,5-dihydro-furan-2-yloxymethyl]-phosphonic acid (2′-Fd4AP) were synthesized and their anti-HIV potency evaluated. The antiviral activity of guanosine analog (2′-Fd4GP) was comparable that of to 2′-Fd4AP in MT-2 cells, but selectivity was reduced.
