524955-87-1Relevant academic research and scientific papers
Synthesis and evaluation of 4-anilino-6, 7-dialkoxy-3-quinolinecarbonitriles as inhibitors of kinases of the Ras-MAPK signaling cascade
Berger, Dan,Dutia, Minu,Powell, Dennis,Wu, Biqi,Wissner, Allan,Boschelli, Diane H.,Floyd, M. Brawner,Zhang, Nan,Torres, Nancy,Levin, Jeremy,Du, Xuemei,Wojciechowicz, Donald,Discafani, Carolyn,Kohler, Constance,Kim, Steven C.,Feldberg, Larry R.,Collins, Karen,Mallon, Robert
, p. 3031 - 3034 (2003)
4-[3-Chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)]anilino-6, 7-diethoxy-3-quinolinecarbonitrile (3) was identified as a MEK1 kinase inhibitor with exceptional activity against LoVo cells. The structure-activity relationships of the C-4 aniline substituents were explored, and water-solubilizing groups were added at the C-7 position to improve physical properties. Secondary cellular assays revealed that a compound possessing the appropriate aniline substituents inhibited MEK1 as well as MAPK phosphorylation, thereby acting as a dual inhibitor of the Ras-MAPK signaling cascade.
Modulation of cAMP-specific PDE without emetogenic activity: New sulfide-like PDE7 inhibitors
García, Ana M.,Brea, José,Morales-García, Jose A.,Perez, Daniel I.,González, Alejandro,Alonso-Gil, Sandra,Gracia-Rubio, Irene,Ros-Simó, Clara,Conde, Santiago,Cadavid, María Isabel,Loza, María Isabel,Perez-Castillo, Ana,Valverde, Olga,Martinez, Ana,Gil, Carmen
, p. 8590 - 8607 (2014/12/11)
A forward chemical genetic approach was followed to discover new targets and lead compounds for Parkinson's disease (PD) treatment. By analysis of the cell protection produced by some small molecules, a diphenyl sulfide compound was revealed to be a new phosphodiesterase 7 (PDE7) inhibitor and identified as a new hit. This result allows us to confirm the utility of PDE7 inhibitors as a potential pharmacological treatment of PD. On the basis of these data, a diverse family of diphenyl sulfides has been developed and pharmacologically evaluated in the present work. Moreover, to gain insight into the safety of PDE7 inhibitors for human chronic treatment, we evaluated the new compounds in a surrogate emesis model, showing nonemetic effects.
