41110-33-2Relevant articles and documents
Design and synthesis of diazine-based panobinostat analogues for HDAC8 inhibition
Balasubramaniam, Sivaraman,Vijayan, Sajith,Goldman, Liam V.,May, Xavier A.,Dodson, Kyra,Adhikari, Sweta,Rivas, Fatima,Watkins, Davita L.,Stoddard, Shana V.
, p. 628 - 637 (2020)
Guided by computational analysis, herein we report the design, synthesis and evaluation of four novel diazine-based histone deacetylase inhibitors (HDACis). The targets of interest (TOI) are analogues of panobinostat, one of the most potent and versatile HDACi reported. By simply replacing the phenyl core of panobinostat with that of a diazine derivative, docking studies against HDAC2 and HDAC8 revealed that the four analogues exhibit inhibition activities comparable to that of panobinostat. Multistep syntheses afforded the visualized targets TOI1, TOI2, TOI3-rev and TOI4 whose biological evaluation confirmed the strength of HDAC8 inhibition with TOI4 displaying the greatest efficacy at varying concentrations. The results of this study lay the foundation for future design strategies toward more potent HDACis for HDAC8 isozymes and further therapeutic applications for neuroblastoma.
ISOXAZOLIDINES AS RIPK1 INHIBITORS AND USE THEREOF
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Page/Page column 146, (2021/12/31)
The present invention relates to isoxazolidines of formula I and their use as receptor-interacting protein kinase 1 inhibitors, for example in the treatment of diseases and disorders mediated by RIP kinase (1) such as rheumatoid arthritis (RA), psoriasis, inflammatory bowel disease (IBD), Crohn's disease or ulcerative colitis.
Discovering a new class of antifungal agents that selectively inhibits microbial carbonic anhydrases
Annunziato, Giannamaria,Giovati, Laura,Angeli, Andrea,Pavone, Marialaura,Del Prete, Sonia,Pieroni, Marco,Capasso, Clemente,Bruno, Agostino,Conti, Stefania,Magliani, Walter,Supuran, Claudiu T.,Costantino, Gabriele
, p. 1537 - 1544 (2018/10/15)
Infections caused by pathogens resistant to the available antimicrobial treatments represent nowadays a threat to global public health. Recently, it has been demonstrated that carbonic anhydrases (CAs) are essential for the growth of many pathogens and their inhibition leads to growth defects. Principal drawbacks in using CA inhibitors (CAIs) as antimicrobial agents are the side effects due to the lack of selectivity toward human CA isoforms. Herein we report a new class of CAIs, which preferentially interacts with microbial CA active sites over the human ones. The mechanism of action of these inhibitors was investigated against an important fungal pathogen, Cryptococcus neoformans, revealing that they are also able to inhibit CA in microbial cells growing in vitro. At our best knowledge, this is the first report on newly designed synthetic compounds selectively targeting β-CAs and provides a proof of concept of microbial CAs suitability as an antimicrobial drug target.
