151707-53-8Relevant academic research and scientific papers
New small molecule inhibitors of histone methyl transferase DOT1L with a nitrile as a non-traditional replacement for heavy halogen atoms
Spurr, Sophie S.,Bayle, Elliott D.,Yu, Wenyu,Li, Fengling,Tempel, Wolfram,Vedadi, Masoud,Schapira, Matthieu,Fish, Paul V.
, p. 4518 - 4522 (2016/08/24)
A number of new nucleoside derivatives are disclosed as inhibitors of DOT1L activity. SARs established that DOT1L inhibition could be achieved through incorporation of polar groups and small heterocycles at the 5-position (5, 6, 12) or by the application of alternative nitrogenous bases (18). Based on these results, CN-SAH (19) was identified as a potent and selective inhibitor of DOT1L activity where the polar 5-nitrile group was shown by crystallography to bind in the hydrophobic pocket of DOT1L. In addition, we show that a polar nitrile group can be used as a non-traditional replacement for heavy halogen atoms.
Selectivity between N-1 and N-7 nucleosides: Regioselective synthesis of BMK-Y101, a potent cdk7 and 9 inhibitor
Kim, Young-Jong,Kwon, Soon Ho,Bae, Il Hak,Kim, B. Moon
, p. 5484 - 5488 (2013/09/23)
BMK-Y101 is a new pyrrolo[2,3-d]pyrimidine-based potent cdk7 and 9 inhibitor, which is characterized by an intriguing structural feature of N-1 nucleoside, departing from previously reported N-7 nucleoside Cdk inhibitor, xylocydine. Though N-1 nucleosides have appeared in the literature, they have often been considered as kinetic products and thus intermediates of N-7 glycosylation. In the course of the synthetic studies of xylocydine derivatives, we have developed a highly regioselective method to obtain the N-1 nucleoside. The origin of the selectivity is apparently based on the reactivity of the silylated nucleobase and the stability of the resulting N-1 nucleoside. The choice of BSA as a silylating agent was critical in securing the N-1 nucleoside, BMK-Y101. On the other hand, proper selection of reaction conditions promoting transglycosylation provides an efficient route to N-7 nucleosides.
Synthesis and evaluation of Janus type nucleosides as potential HCV NS5B polymerase inhibitors
Zhou, Longhu,Amblard, Franck,Zhang, Hongwang,McBrayer, Tamara R.,Detorio, Mervi A.,Whitaker, Tony,Coats, Steven J.,Schinazi, Raymond F.
, p. 3385 - 3388 (2013/06/27)
The synthesis of new ribo and 2′-β-C-methyl ribo Janus type nucleosides J-AA, J-AG and J-AU is reported along with their ability to block HCV and HIV replication. Their toxicity was also assessed in Huh7, human lymphocytes, CEM and Vero cells.
Studies on the glycosylation of pyrrolo[2,3-d] pyrimidines with 1-O-acetyl-2,3,5-tri-O-benzoyl -β-D-ribofuranose: The formation of regioisomers during toyocamycin and 7-deazainosine syntheses
Leonard, Peter,Ingale, Sachin A.,Ding, Ping,Ming, Xin,Seela, Frank
experimental part, p. 678 - 694 (2010/08/06)
Glycosylation of silylated 4-amino-6-bromo-5-cyano-7H-pyrrolo[2,3-d] pyrimidine (9) with 1-O-acetyl-2,3,5-tri-O-benzoyl - d-ribofuranose (10) under "one-pot" glycosylation conditions (MeCN, TMSOTf) yielded the N-7 isomer 11 together with the N-1 compound 13 (ratio = 2:1). When the same conditions were applied to 4-hydroxy-7H-pyrrolo[2,3-d]pyrimidine (21) the N-3 isomer 22 was the only glycosylation product formed in almost quantitative yield.
Total synthesis of the naturally occurring antibiotic toyocamycin using new and improved synthetic procedures
Porcari, Anthony R.,Townsend, Leroy B.
, p. 153 - 159 (2007/10/03)
Starting with commercially available tetracyanoethylene, we describe a more efficient and higher yielding synthesis of toyocamycin with regards to convenience, overall yield, and total reaction time than those syntheses previously reported.
