6022-96-4Relevant articles and documents
Synthesis and evaluation of 3′-fluorinated 7-deazapurine nucleosides as antikinetoplastid agents
Bouton, Jakob,Caljon, Guy,Furquim d'Almeida, Arno,Hulpia, Fabian,Maes, Louis,Van Calenbergh, Serge
, (2021/03/06)
Kinetoplastid parasites are the causative agents of neglected tropical diseases with an unmet medical need. These parasites are unable to synthesize the purine ring de novo, and therefore rely on purine salvage to meet their purine demand. Evaluating purine nucleoside analogs is therefore an attractive strategy to identify antikinetoplastid agents. Several anti-Trypanosoma cruzi and anti-Trypanosoma brucei 7-deazapurine nucleosides were previously discovered, with the removal of the 3′-hydroxyl group resulting in a significant boost in activity. In this work we therefore decided to assess the effect of the introduction of a 3′-fluoro substituent in 7-deazapurine nucleosides on the anti-kinetoplastid activities. Hence, we synthesized two series of 3′-deoxy-3′-fluororibofuranosyl and 3′-deoxy-3′-fluoroxylofuranosyl nucleosides comprising 7-deazaadenine and -hypoxanthine bases and assayed these for antiparasitic activity. Several analogs with potent activity against T. cruzi and T. brucei were discovered, indicating that a fluorine atom in the 3′-position is a promising modification for the discovery of antiparasitic nucleosides.
CYCLIC DINUCLEOTIDES AS STING AGONISTS
-
Paragraph 0086-0087, (2021/01/29)
Disclosed herein are cyclic di-nucleotide compounds and derivatives thereof that may be useful as STING agonists, and a pharmaceutical composition comprising the same. Also disclosed herein is the process for synthesis and to uses of such cyclic di-nucleo
SELECTIVE INHIBITORS OF PROTEIN ARGININE METHYLTRANSFERASE 5
-
Paragraph 0247, (2020/10/20)
The disclosure is directed to methods of treating disease using compounds of Formula (I).