Rook, Yvonne and Schmidtke, Kai-Uwe and Gaube, Friedemann and Schepmann, Dirk and Wuensch, Bernhard and Heilmann, Joerg and Lehmann, Jochen and Winckler, Thomas (2010) Bivalent beta-Carbolines as Potential Multitarget Anti-Alzheimer Agents. JOURNAL OF MEDICINAL CHEMISTRY, 53 (9). pp. 3611-3617. ISSN 0022-2623, 1520-4804
Full text not available from this repository. (Request a copy)Abstract
Alzheimer's disease (AD) is a prevalent neurodegenerative disorder with multifactorial causes that requires multitargeted treatment. Inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) improve cholinergic signaling in the central nervous system and thus AChE inhibitors are well established in the therapy of AD to improve memory disturbances and other cognitive symptoms. On the other hand, AD patients benefit from reduction of pathologic glutamate-induced, Ca2+-mediated excitotoxicity by the N-methyl-D-aspartate receptor (NR) antagonist memantine. New drugs that simultaneously affect both cholinergic transmission and glutamate-induced excitotoxicity may further improve AD treatment. While connecting beta-carboline units by alkylene spacers in two different series of compounds and subsequent evaluation of their AChE/BChE-inhibitory potential, we found that several of these bivalent beta-carbolines were potent NR blockers. The most promising compound was a N-9-homobivalent beta-carboline with a nonylene spacer, which displayed IC50 values of 0.5 nM for AChE, 5.7 nM for BChE, and 1.4 mu M for NR, respectively.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AMINO-ACID RECEPTORS; NMDA RECEPTOR; ASPARTATE; ACETYLCHOLINESTERASE; INHIBITORS; GLUTAMATE; ANTAGONISTS; CHANNELS; LIGANDS; DISEASE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jul 2020 11:12 |
| Last Modified: | 30 Jul 2020 11:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24735 |
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