18342-97-7Relevant articles and documents
Design, Synthesis, and Evaluation of the Highly Selective and Potent G-Protein-Coupled Receptor Kinase 2 (GRK2) Inhibitor for the Potential Treatment of Heart Failure
Okawa, Tomohiro,Aramaki, Yoshio,Yamamoto, Mitsuo,Kobayashi, Toshitake,Fukumoto, Shoji,Toyoda, Yukio,Henta, Tsutomu,Hata, Akito,Ikeda, Shota,Kaneko, Manami,Hoffman, Isaac D.,Sang, Bi-Ching,Zou, Hua,Kawamoto, Tetsuji
, p. 6942 - 6990 (2017/09/07)
A novel class of therapeutic drug candidates for heart failure, highly potent and selective GRK2 inhibitors, exhibit potentiation of β-adrenergic signaling in vitro studies. Hydrazone derivative 5 and 1,2,4-triazole derivative 24a were identified as hit compounds by HTS. New scaffold generation and SAR studies of all parts resulted in a 4-methyl-1,2,4-triazole derivative with an N-benzylcarboxamide moiety with highly potent activity toward GRK2 and selectivity over other kinases. In terms of subtype selectivity, these compounds showed enough selectivity against GRK1, 5, 6, and 7 with almost equipotent inhibition to GRK3. Our medicinal chemistry efforts led to the discovery of 115h (GRK2 IC50 = 18 nM), which was obtained the cocrystal structure with human GRK2 and an inhibitor of GRK2 that potentiates β-adrenergic receptor (βAR)-mediated cAMP accumulation and prevents internalization of βARs in β2AR-expressing HEK293 cells treated with isoproterenol. Therefore, 115h appears to be a novel class of therapeutic for heart failure treatment.
CONDENSED TRICYCLIC COMPOUNDS AS PROTEIN KINASE INHIBITORS
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Page/Page column 108, (2017/03/14)
There is provided compounds of formula I, (I) wherein R1, R2, R3 R4, R5, R6, R7a and R7b have meanings given in the description, and pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protein or lipid kinase (e.g. CDK8 and/or Haspin kinase) is desired and/or required, and particularly in the treatment of cancer or a proliferative disease.
AMIDO-BENZYL SULFONE AND SULFOXIDE DERIVATIVES
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Page/Page column 128, (2013/09/12)
The present invention relates to certain amido-benzyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.
PYRIDINYL AND PYRIMIDINYL SULFOXIDE AND SULFONE DERIVATIVES
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Page/Page column 79; 80, (2013/09/12)
Disclosed are certain pyridinyl and pyrimidinyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds and methods of treatment using such compounds.
AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES
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Page/Page column 141, (2013/09/12)
Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.
AMIDO-BENZYL SULFONE AND SULFONAMIDE DERIVATIVES
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Page/Page column 57; 58, (2013/09/12)
Disclosed are certain amido-benzyl sulfone and sulfonamide compounds, pharmaceutical compositions comprising such compounds, land methods of treatment using such compounds.
AMIDO-BENZYL SULFOXIDE DERIVATIVES
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Paragraph 0166, (2013/09/12)
The present invention relates to certain amido-benzyl sulfoxide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment of an NAMPT-mediated disease or condition in a subject, selected from solid or liquid tumor, rheumat
ALKYL-AND DI-SUBSTITUTED AMIDO-BENZYL SULFONAMIDE DERIVATIVES
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Paragraph 0174, (2013/09/12)
The present invention relates to certain alkyl- and di-substituted amido-benzyl sulfonamide compounds, pharmaceutical compositions comprising such compounds, and to methods of treatment of NAMPT-mediated disorders, such as diabetes, rheumatoid arthritis,
AZA-BENZOFURANYL COMPOUNDS AND METHODS OF USE
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Page/Page column 68, (2008/06/13)
The invention relates to azabenzofuranyl compounds of Formula (I) with anti-cancer and/or anti-inflammatory activity and more specifically to azabenzofuranyl compounds which inhibit MEK kinase activity. The invention provides compositions and methods useful for inhibiting abnormal cell growth or treating a hyperproliferative disorder, or treating an inflammatory disease in a mammal. The invention also relates to methods of using the compounds for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.
Raf inhibitor compounds and methods of use thereof
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Page/Page column 78; 30-31, (2010/11/26)
Compounds of Formula I are useful for inhibiting Raf kinase and for treating disorders mediated thereby. Methods of using compounds of Formula I, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.
