146073-02-1Relevant articles and documents
N-arylsulfonylindole derivatives as serotonin 5-HT6 receptor ligands
Russell,Baker,Barden,Beer,Bristow,Broughton,Knowles,McAllister,Patel,Castro
, p. 3881 - 3895 (2007/10/03)
A series of N1-arylsulfonyltryptamines were found to be potent ligands of the human serotonin 5-HT6 receptor with the 5-methoxy-1-benzenesulfonyl analogue (19) having the highest affinity. Additionally, it was discovered that a group such as 3-(3-methoxybenzyl)-1,2,4-oxadiazol-5-yl in the 2-position of the indole ring (43) can replace the arylsulfonyl substituent in the 1-position with no loss of affinity. This suggested that the binding conformation of the aminoethyl side chain at this receptor was toward the 4-position of the indole ring and was supported by the fact that the 4-(aminoethyl)indoles (45) also displayed high affinity, as did the conformationally rigid 1,3,4,5-tetrahydrobenz[c,d]indole (49). Molecular modeling showed that 19, 43, and 45 all had low-energy conformers that overlaid well onto 49. Both 19 and 49 had good selectivity over other serotonin receptors tested, with 49 also showing excellent selectivity over all dopamine receptors. In a functional adenylate cyclase stimulation assay, 19 and 49 had no agonist activity, whereas 45 behaved as a partial agonist. Finally, it was shown that 19 had good activity in the 5-HT2A centrally mediated mescaline-induced head twitch assay, which implies that it is brain-penetrant.
Indole and indoline derivatives as 5-HT6 selective ligands
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, (2008/06/13)
Three classes of indole and indoline derivatives are disclosed as ligands selective for the 5-HT6receptors, and hence of value in the treatment or prevention of CNS disorders, including Alzheimer's disease, Parkinson's disease, schizophrenia, depression and anxiety. A particular class, 1-substituted-4-(ω-N,N-dialkyl-aminoalkyl)indoles, are claimed as novel compounds.
A novel approach to the skeletons of the ergot alkaloids and secoergolines
Mann, John,Barbey, Sabine
, p. 12763 - 12774 (2007/10/02)
An efficient eight-stage synthesis of N-benzenesulphonyl-3-(3'-methoxyprop-2'-en-1'-yl)-4-(1'-hydroxy-2'-tri methylsilylmethyl-prop-2'-en-1'-yl)-indoles from 4-carbomethoxyindole is described, together with the use of these benzylic alcohols for intramolecular cation-olefine cycloadditions that yield either a tetracyclic product (suitable for elaboration into ergot alkaloids) or a tricyclic product (suitable for elaboration into secoergolines) depending upon the reaction conditions.
Preparation of alkyl-substituted indoles in the benzene portion. Part 5. Efficient preparative procedure for 4-substituted indole derivatives
Fuji,Muratake,Natsume
, p. 2338 - 2343 (2007/10/02)
An effective and short synthetic method for 4-substituted indole derivatives was developed based on the two sequential reactions, i.e. nucleophilic addition of carbanions to common precursor molecules, 3-(1,3-dioxolan-2-yl)-1-[1(phenylsulfonyl)- and 1-[(4
