Details

Autor(en) / Beteiligte

• Lehmann, Fredrik
• Currier, Erika A.
• Olsson, Roger
• Ma, Jian-Nong
• Burstein, Ethan S.
• Hacksell, Uli
• Luthman, Kristina

Titel

Optimization of isochromanone based urotensin II receptor agonists

Ist Teil von

• Bioorganic & medicinal chemistry, 2010-07, Vol.18 (13), p.4844-4854

Ort / Verlag

Amsterdam: Elsevier Ltd

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• A series of novel isochromanone based urotensin II receptor agonists have been synthesized and evaluated for their activity using a functional cell based assay (R-SAT). Several potent and efficacious derivatives were identified with 3-(3,4-dichlorophenyl)-6,7-dimethyl-3-(2-dimethylaminoethyl)isochroman-1-one ( 28) being the most potent compound showing an EC 50-value of 51 nM, thereby being the most potent compound so far within the isochromanone series. In addition, two other heterocyclic systems (isochromanes and tetrahydroisoquinolinones) were investigated and these derivatives were found to be both potent and efficacious. The activity of the isochromane derivatives implies that the carbonyl group of the isochromanone is not necessary for activity. Furthermore it was found that the geometry of the heterocycles was more important for receptor interaction than the composition of the heteroatoms present.