Rook_2010_J.Med.Chem_53_3611

Reference

Title : Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents - Rook_2010_J.Med.Chem_53_3611
Author(s) : Rook Y , Schmidtke KU , Gaube F , Schepmann D , Wunsch B , Heilmann J , Lehmann J , Winckler T
Ref : Journal of Medicinal Chemistry , 53 :3611 , 2010
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, Ca(2+)-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 IC(50) values of 0.5 nM for AChE, 5.7 nM for BChE, and 1.4 microM for NR, respectively.

PubMedSearch : Rook_2010_J.Med.Chem_53_3611
PubMedID: 20361801

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Citations formats

Rook Y, Schmidtke KU, Gaube F, Schepmann D, Wunsch B, Heilmann J, Lehmann J, Winckler T (2010)
Bivalent beta-carbolines as potential multitarget anti-Alzheimer agents
Journal of Medicinal Chemistry 53 :3611

Rook Y, Schmidtke KU, Gaube F, Schepmann D, Wunsch B, Heilmann J, Lehmann J, Winckler T (2010)
Journal of Medicinal Chemistry 53 :3611