Discovery, synthesis and biological evaluation of isoquinolones as novel and highly selective JNK inhibitors (2)
3-Metoxycarbonyl isoquinolone derivative 1 has been identified as a potent JNK inhibitor and significantly inhibited cardiac hypertrophy in a rat pressure-overload model. Herein, a series of isoquinolones with an imidazolylmethyl or a pyrazolylmethyl group at the 2-position were designed based on X-ray crystallographic analysis of the complex between the isoquinolone compound and JNK3, as wells as the relationship between compound lipophilicity (log D) and activity in a cell-based assay. The compounds prepared showed potent JNK1 inhibitory activities in a cell-based assay. Among them the isoquinolone derivative possessing 5-[(cyclopropylamino)carbonyl]-1-methyl-1H-pyrazole (16e) exhibited significant anti-hypertrophic activity at doses of more than 1 mg/kg (po) in a pressure-overload model.
Le dimethylacetal du diazoacetaldehyde: une nouvelle voie d'acces aux formylcyclopropanes et aux formyl pyrazoles
Formylcyclopropanes are conveniently obtained through reaction of diazoacetaldehyde dimethylacetal 1 even with olefins which are not highly electrophilic (styrene, cinnamaldehydeacetal, cyanocyclopentene for instance).Only 3,5-disubstituted formylpyrazole
Abdallah, H.,Gree, R.,Carrie, R.
p. 794 - 802
(2007/10/02)
LE DIMETHYL ACETAL DU DIAZOACETALDEHYDE : UNENOUVELLE VOIE D'ACCES AUX CYCLOPROPANES ALDEHYDES ET AUX FORMYL PYRAZOLES.
Diazoacetaldehyde dimethylacetal 1 is a readily accessible and highly reactive 1,3 dipole.Starting from 1, both electrophilic cyclopropanes with an extra aldehyde function and formyl pyrazoles are prepared in high yields.
Abdallah, Hassan,Gree, Rene
p. 2239 - 2242
(2007/10/02)
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