- 3,5-Disubstituted-indole-7-carboxamides as IKKβ Inhibitors: Optimization of Oral Activity via the C3 Substituent
-
IκB kinase β (IKKβ or IKK2) is a key regulator of nuclear factor kappa B (NF-κB) and has received attention as a therapeutic target. Herein we report on the optimization of a series of 3,5-disubstituted-indole-7-carboxamides for oral activity. In doing so
- Kerns, Jeffrey K.,Busch-Petersen, Jakob,Fu, Wei,Boehm, Jeffrey C.,Nie, Hong,Muratore, Michael,Bullion, Ann,Lin, Guoliang,Li, Huijie,Davis, Roderick,Lin, Xichen,Lakdawala, Ami S.,Cousins, Rick,Field, Rita,Payne, Jeremy,Miller, David D.,Bamborough, Paul,Christopher, John A.,Baldwin, Ian,Osborn, Ruth R.,Yonchuk, John,Webb, Edward,Rumsey, William L.
-
p. 1164 - 1169
(2018/11/23)
-
- SELECTIVE INHIBITORS OF CLINICALLY IMPORTANT MUTANTS OF THE EGFR TYROSINE KINASE
-
The present invention provides compounds of Formula (I) or a subgeneric structure or species thereof, or a pharmaceutically acceptable salt, ester, solvate, and/or prodrug thereof, and methods and compositions for treating or ameliorating abnormal cell proliferative disorders, such as cancer, wherein A, R2, R3, R10, E1, E2, E3, Y, and Z are as defined herein.
- -
-
-
- CD38 INHIBITORS AND METHODS OF TREATMENT
-
Compounds of Formula (I) and methods of treating diseases of metabolism by modulating cellular NAD+ levels through the inhibition of the CD38 enzyme, are disclosed. Formula (I).
- -
-
-
- 3,5-Disubstituted-indole-7-carboxamides: The discovery of a novel series of potent, selective inhibitors of IKK-β
-
The discovery and hit-to-lead exploration of a novel series of selective IKK-β kinase inhibitors is described. The initial lead fragment 3 was identified by pharmacophore-directed virtual screening. Homology model-driven SAR exploration of the template le
- Miller, David D.,Bamborough, Paul,Christopher, John A.,Baldwin, Ian R.,Champigny, Aurelie C.,Cutler, Geoffrey J.,Kerns, Jeffrey K.,Longstaff, Timothy,Mellor, Geoffrey W.,Morey, James V.,Morse, Mary A.,Nie, Hong,Rumsey, William L.,Taggart, John J.
-
p. 2255 - 2258
(2011/05/15)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to novel indole carboxamide derivatives. Specifically, the invention is directed to compounds according to formula I: where R1, R2, R3, U and V are defined below and to pharmaceutically acceptable salts thereof. The compounds of the invention are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKβ) activity, such as rheumatoid arthritis, asthma, and COPD (chronic obstructive pulmonary disease). Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
-
- INDOLE CARBOXAMIDES AS IKK2 INHIBITORS
-
The invention is directed to novel indole carboxamide compounds. Specifically, the invention is directed to compounds according to formula (I): wherein R1, R2, R3, R4, and m are as defined herein. The compounds of the invention are inhibitors of IKK2 and can be useful in the treatment of disorders associated with inappropriate IKK2 (also known as IKKβ) activity, such as rheumatoid arthritis, asthma, rhinitis, and COPD (chronic obstructive pulmonary disease). Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting IKK2 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
- -
-
Page/Page column 69-70
(2008/12/04)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to novel indolecarboxamide derivatives, Specifically, the invention is directed to compounds according to formula (I), where R1 , R2, R3 and X are defined below. These compounds are useful in the treatment of disorders associated
- -
-
Page/Page column 39
(2010/11/27)
-
- Indole, indazole and indoline derivatives as CETP inhibitors
-
The present invention relates to compounds of formula (I): wherein —X—Y—, R1 to R11 and n are as defined in the description and claims, and pharmaceutically acceptable salts thereof. The compounds are useful for the treatment and/or prevention of diseases which are mediated by CETP inhibitors.
- -
-
Page/Page column 22
(2010/02/15)
-
- CHEMICAL COMPOUNDS
-
The invention is directed to novel indole carboxamide derivatives. Specifically, the invention is directed to compounds according to formula (1): where R1, R2, R3, U and V are defined below and to pharmaceutically acceptable salts thereof. The compounds o
- -
-
Page/Page column 73
(2010/10/20)
-
- INDOLE DERIVATIVES AND USE THEREOF AS KINASE INHIBITORS IN PARTICULAR IKK2 INHIBITORS
-
Indole carboxamide compounds of Formula (I): are provided as inhibitors of kinase activity, in particular IKK2 activity as well as compositions and medicaments containing them, for use in inflammatory and tissue repair disorders.
- -
-
Page/Page column 38-39
(2010/02/13)
-