کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1378025 | 981992 | 2007 | 4 صفحه PDF | دانلود رایگان |
Relying on the high affinities of the benz-indolo-azecine LE 300 (1) and the hydroxylated dibenz-azecine LE 404 (2b) for the D1/D5 receptor subtypes, we synthesized methoxylated, hydroxylated and an indole-N methylated derivatives of 1 (Fig. 1). Hydroxylation of azecine derivatives is beneficial with regard to the affinities and selectivities for all the dopamine receptor subtypes. The ‘serotonin-derived’ 3-oxygenated target compounds but not the 11-oxygenated analogues were superior to the unsubstituted LE 300. 11-Methoxy-7,14-dimethyl-6,7,8,9,14,15-hexahydro-5H-indolo[3,2-f][3]benzazecine (3e) was found to be the most potent antagonist at D2/D3/D4 and D5 receptor subtypes (Ki for D5 = 0.23 nmol) of all known benz-indolo-azecines.
To explore SAR, the synthesis of novel azecine-styled dopamine antagonists and screening was performed at all human-cloned dopamine receptor subtypes. The benz-indolo-azecine with the highest affinity for D5 until now, turned out to be 3eKi = 0.23 nM.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 17, Issue 5, 1 March 2007, Pages 1399–1402