- FORMAMIDE COMPOUND, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
-
The present invention relates to a formamide compound, a preparation method therefor and an application thereof. The structure of the compound is shown in formula (I), and the definition of each variable in the formula is as provided in the description. The compound is capable of inhibiting the activity of ASK1 kinase. The compound of the present invention may be used in the treatment/prevention of diseases associated with ASK1 kinase, such as inflammatory diseases, metabolic diseases, autoimmune diseases, cardiovascular diseases, neurodegenerative diseases, cancers and other diseases.
- -
-
Paragraph 0146-0147
(2021/05/14)
-
- Discovery of Potent Benzolactam IRAK4 Inhibitors with Robust in Vivo Activity
-
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.
- 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.
-
supporting information
p. 327 - 333
(2019/12/02)
-
- PYRIDINE DERIVATIVE AS ASK1 INHIBITOR AND PREPARATION METHOD AND USE THEREOF
-
Disclosed in the present invention are a compound as shown in formula (II), a tautomer or a pharmaceutically acceptable salt thereof, and also disclosed is the use thereof in preparing a drug for treating an ASK1-associated disease.
- -
-
Paragraph 0123-0125
(2019/12/05)
-
- PYRAZOLO[1,5a]PYRIMIDINE DERIVATIVES AS IRAK4 MODULATORS
-
Compounds of Formula (0), Formula (I), and Formula (II) and methods of use as Interleukin-1 Receptor Associated Kinase (IRAK4) inhibitors are described herein.
- -
-
Page/Page column 407
(2017/07/14)
-
- GONADOTROPIN-RELEASING HORMONE RECEPTOR ANTAGONISTS AND METHODS RELATING THERETO
-
GnRH receptor antagonists are disclosed which have utility in the treatment of a variety of sex-hormone related conditions in both men and women. The compounds of this invention have the structure, wherein R1a, R1b, R1c, R1d, R2, R2a, and A are as defined herein, including stereoisomers, esters, solvates and pharmaceutically acceptable salts thereof. Also disclosed are compositions containing a compound of this invention in combination with a pharmaceutically acceptable carrier, as well as methods relating to the use thereof for antagonizing gonadotropin-releasing hormone in a subject in need thereof.
- -
-
Page/Page column 92; 93
(2008/12/04)
-