Tetrahydrobenzothiophene carboxamides: Beyond the kinase domain and into the fatty acid realm
A series of tetrahydrobenzothiophene carboxamides, inspired by structural features present in kinase and SCD1 inhibitors, are presented here. Prototype compound 8 (MMDD13) modulates fatty acid elongase and desaturase indexes, lipid accumulation, while pre
Llona-Minguez, Sabin,Fayezi, Shabnam,Alihemmati, Alireza,Juárez-Jiménez, Jordi,Piedrafita, F. Javier,Helleday, Thomas
supporting information
p. 4462 - 4466
(2017/09/12)
Aryl extensions of thienopyrimidinones as fibroblast growth factor receptor 1 kinase inhibitors
Optimization of thienopyrimidinone derivatives as FGFR1 kinase inhibitors is being pursued. The present results confirm predictions of computational modeling that an aryl substituent can be introduced at the 2-position in structure 3. The substituent is anticipated to project deeper into the binding site and provide opportunities for enhanced activity and selectivity. The most potent analog reported herein, 13, has a 4-hydroxyphenyl substituent and yields an IC50 of 6 μM for inhibition of phosphorylation by FGFR1 kinase. It was also found that the western anisole-containing substituent in 3 can be replaced by a propionic acid group with no loss in potency and with potentially significant gains in pharmacologically relevant properties.
Ekkati, Anil R.,Mandiyan, Valsan,Ravindranathan, Krishna P.,Bae, Jae H.,Schlessinger, Joseph,Jorgensen, William L.
scheme or table
p. 2228 - 2231
(2011/05/05)
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