Synthesis of potential Rho-kinase inhibitors based on the chemistry of an original heterocycle: 4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one.
A new series of substituted 4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one have been prepared via condensation of 3,3-dimethylacryloyl chloride with aniline. Details of synthetic procedures are shown. Our aim was to investigate the potency of our original heterocycle in the inhibition of the Rho-kinase enzyme, known to be of major importance in the cascade reactions leading to arterial hypertension. Biological activity for the seven compounds has been investigated and is presented.
Letellier
Marie-Anne
MA
Laboratoire de Chimie Organique, EA 3857, UFR des Sciences Pharmaceutiques, 31 Avenue Monge, 37200 Tours, France.
Guillard
Jérôme
J
Caignard
Daniel-Henri
DH
Ferry
Gilles
G
Boutin
Jean A
JA
Viaud-Massuard
Marie-Claude
MC
D001665:Binding Sites; D002384:Catalysis; D003432:Cross-Linking Reagents; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D003432:Cross-Linking Reagents; D008024:Ligands; D047428:Protein Kinase Inhibitors; D015363:Quinolones; D011994:Recombinant Proteins; D054460:rho-Associated Kinases