158205-18-6Relevant articles and documents
Discovery of Potent Benzolactam IRAK4 Inhibitors with Robust in Vivo Activity
Rajapaksa, Naomi S.,Gobbi, Alberto,Drobnick, Joy,Do, Steven,Kolesnikov, Aleksandr,Liang, Jun,Chen, Yongsheng,Sujatha-Bhaskar, Swathi,Huang, Zhiyu,Brightbill, Hans,Francis, Ross,Yu, Christine,Choo, Edna F.,Dement, Kevin,Ran, Yingqing,An, Le,Emson, Claire,Maher, Jonathan,Wai, John,McKenzie, Brent S.,Lupardus, Patrick J.,Zarrin, Ali A.,Kiefer, James R.,Bryan, Marian C.
, p. 327 - 333 (2019/12/02)
IRAK4 kinase activity transduces signaling from multiple IL-1Rs and TLRs to regulate cytokines and chemokines implicated in inflammatory diseases. As such, there is high interest in identifying selective IRAK4 inhibitors for the treatment of these disorders. We previously reported the discovery of potent and selective dihydrobenzofuran inhibitors of IRAK4. Subsequent studies, however, showed inconsistent inhibition in disease-relevant pharmacodynamic models. Herein, we describe application of a human whole blood assay to the discovery of a series of benzolactam IRAK4 inhibitors. We identified potent molecule 19 that achieves robust in vivo inhibition of cytokines relevant to human disease.
PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS
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, (2019/01/10)
Compounds of Formula (I), Formula (II), Formula (III), Formula (IV), Formula (V), Formula (VI), Formula (VII), Formula (VIII), and methods of use as lnterleukin-1 Receptor Associated Kinase (IRAK4) inhibitors are described herein.
PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS
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, (2017/07/14)
Compounds of Formula (0), Formula (I), and Formula (II) and methods of use as Interleukin-1 Receptor Associated Kinase (IRAK4) inhibitors are described herein.
A structure-guided approach to an orthogonal estrogen-receptor-based gene switch activated by ligands suitable for in vivo studies
Kinzel, Olaf,Fattori, Daniela,Muraglia, Ester,Gallinari, Paola,Nardi, Maria Chiara,Paolini, Chantal,Roscilli, Giuseppe,Toniatti, Carlo,Gonzalez Paz, Odalys,Laufer, Ralph,Lahm, Armin,Tramontano, Anna,Cortese, Riccardo,De Francesco, Raffaele,Ciliberto, Gennaro,Koch, Uwe
, p. 5404 - 5407 (2007/10/03)
A strategy to obtain a fully orthogonal estrogen-receptor-based gene switch responsive to molecules with acceptable pharmacological properties is presented. From a series of tetrahydrofluorenones active on the wild-type estrogen receptor (ER) an inactive
Antifolate chemistry: Synthesis of 4-{N-[(6RS)-2-methyl-4-oxo- 3,4,7,8-tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoic acid via a (propargyl)Co2(CO)6+ complex
Bavetsias, Vassilios,Clauss, Rainer,Henderson, Elisa A.
, p. 1943 - 1946 (2007/10/03)
A new route to compound 3 (4-{N-[(6RS)-2-methyl-4-oxo-3,4,7,8- tetrahydro-6H-cyclopenta[g]quinazolin-6-yl]-N-(prop-2-ynyl)amino}benzoic acid), a crucial intermediate for the synthesis of potent inhibitors of thymidylate synthase (TS), is described. In this sequence the C6-N10 bond was constructed first, by the reductive amination of 5-acetamido-6-bromoindan-1-one 6 with tert-butyl 4-aminobenzoate, then the cyclopenta[g]quinazolinone ring was formed and the propargyl group was introduced on the N10-position using the (propargyl)Co2(CO)6+ complex as the electrophilic propargyl reagent.
5-methanesulfonamido-1-indanones as an inhibitor of cyclooxygenase-2
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, (2008/06/13)
The Compound of Formula I and pharmaceutically acceptable salts thereof in the treatment of cyclooxygenase-2 mediated diseases are disclosed.
Cyclooxygenase-2 inhibitors. Synthesis and pharmacological activities of 5-methanesulfonamido-1-indanone derivatives
Li,Black,Chan,Ford-Hutchinson,Gauthier,Gordon,Guay,Kargman,Lau,Mancini,Ouimet,Roy,Vickers,Wong,Young,Zamboni,Prasit
, p. 4897 - 4905 (2007/10/03)
The recent discovery of an alternative form cyclooxygenase (cyclooxygenase-2, COX-2), which has been proposed to play a significant role in inflammatory conditions, may provide an opportunity to develop anti- inflammatory drugs with fewer side effects tha
Synthesis of 5-methanesulfonamido-6-(2,4-difluorophenylthio)-1-indanone
Scheigetz,Zamboni,Roy
, p. 2791 - 2806 (2007/10/02)
The ethylene ketal of 5-nitro-6-bromo-1-indanone 6 was prepared via oxidation of N-(6-Bromo-5-indanyl)-acetamide 1. A subsequent mild displacement and elaboration to 6-thiosubstituted-5-amino indanone derivative 10 is also described.
ALKANESULFONAMIDO-1-INDANONE DERIVATIVES AS INHIBITORS OF CYCLOOXYGENASE
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, (2008/06/13)
Disclosed are compounds of Formula I useful in the treatment of cyclooxygenase mediated diseases such as pain, fever and inflammation of a variety of conditions including rheumatic fever, symptoms associated with influenza or other viral infections, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, myositis, neuralgia, synovitis, arthritis, including rheumatoid arthritis degenerative joint diseases (osteoarthritis), gout and ankylosing spondylitis, bursitis, bums, injuries