88571-77-1Relevant academic research and scientific papers
HPK1 INHIBITORS, PREPARATION METHOD AND APPLICATION THEREOF
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Page/Page column 110-111, (2019/11/12)
Disclosed are HPK-1 inhibitors having a structure represented by Formula (X), pharmaceutical compositions comprising the HPK-1 inhibitors, methods of using the HPK-1 inhibitors, such as treating cancers, methods of preparing the HPK-1 inhibitors, and the synthetic intermediates.
Optimization of diarylthiazole B-Raf inhibitors: Identification of a compound endowed with high oral antitumor activity, mitigated hERG inhibition, and low paradoxical effect
Pulici,Traquandi,Marchionni,Modugno,Lupi,Amboldi,Casale,Colombo,Corti,Fasolini,Gasparri,Pastori,Scolaro,Donati,Felder,Galvani,Isacchi,Pesenti,Ciomei
, p. 276 - 295 (2015/02/05)
Aberrant activation of the mitogen-activated protein kinase (MAPK)-mediated pathway components, RAF-MEK-ERK, is frequently observed in human cancers and clearly contributes to oncogenesis. As part of a project aimed at finding inhibitors of B-Raf, a key player in the MAPK cascade, we originally identified a thiazole derivative endowed with high potency and selectivity, optimal in vitro ADME properties, and good pharmacokinetic profiles in rodents, but that suffers from elevated hERG inhibitory activity. An optimization program was thus undertaken, focused mainly on the elaboration of the R1 and R2 groups of the scaffold. This effort ultimately led to N-(4-{2-(1-cyclopropylpiperidin-4-yl)-4-[3-(2,5-difluorobenzenesulfonylamino)-2-fluorophenyl]thiazol-5-yl}-pyridin-2-yl)acetamide (20), which maintains favorable in vitro and in vivo properties, but lacks hERG liability. Besides exhibiting potent antiproliferative activity against only cell lines bearing B-Raf V600E or V600D mutations, compound 20 also intriguingly shows a weaker "paradoxical" activation of MEK in non-mutant B-Raf cells than other known B-Raf inhibitors. It also demonstrates very good efficacy in vivo against the A375 xenograft melanoma model (tumor volume inhibition >90% at 10 mg kg-1); it is therefore a suitable candidate for preclinical development.
THIAZOLYLPHENYL-BENZENESULFONAMIDO DERIVATIVES AS KINASE INHIBITORS
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, (2014/01/07)
Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
THIAZOLYLPHENYL-BENZENESULFONAMIDO DERIVATIVES AS KINASE INHIBITORS
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, (2012/09/11)
Thiazolylphenyl-benzenesulfonamido derivatives of formula (I) as defined in the specification, and pharmaceutically acceptable salts thereof, process for their preparation and pharmaceutical compositions comprising them are disclosed; the compounds of the invention may be useful, in therapy, in the treatment of diseases associated with a disregulated protein kinase activity, like cancer.
BENZENE SULFONAMIDE THIAZOLE AND OXAZOLE COMPOUNDS
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Page/Page column 106-107, (2011/06/16)
The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
Benzene Sulfonamide Thiazole and Oxazole Compounds
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Page/Page column 49, (2009/12/23)
The present invention provides thiazole sulfonamide and oxazole sulfonamide compounds, compositions containing the same, as well as processes for the preparation and methods for their use as pharmaceutical agents.
NITROGEN-CONTAINING HETEROCYCLIC COMPOUND AND PHARMACEUTICAL APPLICATION THEREOF
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Page/Page column 79, (2010/11/26)
It is intended to provide a compound represented by the general formula (I): (I) (wherein all the symbols are as defined in the description) which has a p38 MAP kinase inhibitory activity, a salt thereof, an N-oxide thereof, a solvate thereof, or a prodrug thereof. The compound of the invention is useful for preventing or treating a disease in which the abnormal production of a cytokine such as an inflammatory cytokine or a chemokine or overreaction to them is considered to be involved in the cause and aggravation of pathological conditions, in other words, an inflammatory disease, a respiratory disease, a cardiovascular disease, a central nervous system disease or the like, which is a cytokine-mediated disease.
