- Discovery of Orally Bioavailable Ligand Efficient Quinazolindiones as Potent and Selective Tankyrases Inhibitors
-
We report herein the discovery of quinazolindiones as potent and selective tankyrase inhibitors. Elucidation of the structure-activity relationship of the lead compound 1g led to truncated analogues that have good potency in cells, pharmacokinetic (PK) properties, and excellent selectivity. Compound 21 exhibited excellent potencies in cells and proliferation studies, good selectivity, in vitro activities, and an excellent PK profile. Compound 21 also inhibited H292 xenograft tumor growth in nude mice. The synthesis, biological, pharmacokinetic, in vivo efficacy studies, and safety profiles of compounds are presented.
- Qin, Donghui,Lin, Xiaojuan,Liu, Zhi,Chen, Yan,Zhang, Zhiliu,Wu, Chengde,Liu, Linlin,Pan, Yan,Laquerre, Sylvie,Emery, John,Fergusson, Jeff,Roland, Kimberly,Keenan, Rick,Oliff, Allen,Kumar, Sanjay,Cheung, Mui,Su, Dai-Shi
-
p. 1005 - 1010
(2021/05/27)
-
- BISARYL AMIDES AS NRF2 REGULATORS
-
The present invention relates to bisaryl amide analogs, pharmaceutical compositions containing them and their use as NRF2 activators. In particular, the invention relates to bisaryl heterocycles of Formula (I).
- -
-
Page/Page column 336
(2018/09/11)
-
- QUINAZOLINEDIONES AS TANKYRASE INHIBITORS
-
This invention relates to the use of quinazolinediones for the modulation, notably the inhibition of the activity of tankyrases (TNKS1 and TNKS2). Suitably, the present invention relates to the use of quinazolinediones in the treatment of cancer, fibrosis and other hyperproliferative diseases through this mechanism.
- -
-
-
- Isoxazole derivatives
-
An isoxazole compound having the following formula: wherein R1 represents hydrogen, halogen, alkyl, alkoxy, hydroxyl, alkylthio, amino, alkanoyl, alkanoylamino, alkanoyloxy, alkoxycarbonyl, carboxy, (alkylthio)thiocarbonyl, carbamoyl, nitro or cyano; R2 represents an amino; m is 1; n is 1 to 6; ring A represents a phenyl ring or a naphthyl ring; and X represents oxygen or sulfur. The isoxazole compound has an excellent monoamine oxidase inhibitory activity, and is useful for treating Parkinson's disease, depression and Alzheimer's disease.
- -
-
-