Iridium-Catalyzed β-C(sp2)?H Borylation of Enamides – Access to 3,3-Dihalogeno-2-methoxypiperidines
An efficient catalytic preparation of synthetically useful new β-borylated enamides was achieved under relatively mild conditions via a regioselective iridium-catalyzed C(sp2)?H borylation. The method features broad substrate scope, good functi
Discovery of indazole-pyridinone derivatives as a novel class of potent and selective MNK1/2 kinase inhibitors that protecting against endotoxin-induced septic shock
The mitogen-activated protein kinase (MAPK)-interacting kinases 1 and 2 (MNKs 1/2) and their downstream target eIF4E, play a role in oncogenic transformation, progression and metastasis. These results provided rationale for development of first MNKs inhibitors, currently in clinical trials for cancer treatment. Inhibitors of the MNKs/eIF4E pathway are also proposed as treatment strategy for inflammatory conditions. Here we present results of optimization of indazole-pyridinone derived MNK1/2 inhibitors among which compounds 24 and 26, selective and metabolically stable derivatives. Both compounds decreased levels of eIF4E Ser206 phosphorylation (pSer209-eIF4E) in MOLM16 cell line. When administered in mice compounds 24 and 26 significantly improved survival rates of animals in the endotoxin lethal dose challenge model, with concomitant reduction of proinflammatory cytokine levels – TNFα and IL-6 in serum. Identified MNK1/2 inhibitors represent a novel class of immunomodulatory compounds with a potential for the treatment of inflammatory diseases including sepsis.
PYRIDONE DERIVATIVES AND THEIR USE AS KINASE INHIBITORS
Disclosed in the present application is a compound of formula (I) as defined herein as well as a pharmaceutical composition comprising said compound. Further disclosed in the present application is the use of such pharmaceutical compositions for treating diseases, namely inter alia for use in the treatment of cancer, metabolic, inflammatory, autoimmune and viral diseases. The compounds disclosed herein are inhibitors of MNK1 and/or MNK2 kinases.
-
Page/Page column 171; 172; 174
(2017/05/10)
Novel Heterocyclic Compounds as Bromodomain Inhibitors
The present disclosure relates to compounds, which are useful for inhibition of BET protein function by binding to bromodomains, and their use in therapy.
-
(2014/07/08)
INHIBITORS OF VIRAL REPLICATION, THEIR PROCESS OF PREPARATION AND THEIR THERAPEUTICAL USES
Inhibitors of viral replication of formula (I), their process of preparation and their therapeutical uses. The present invention relates to compounds, their use in the treatment or the prevention of viral disorders, including HIV.
-
Page/Page column 137; 139
(2014/05/07)
More Articles about upstream products of 1594127-49-7