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| Item type: | Article | ||||
|---|---|---|---|---|---|
| Journal or Publication Title: | Journal of medicinal chemistry | ||||
| Publisher: | American Chemical Society | ||||
| Volume: | 53 | ||||
| Number of Issue or Book Chapter: | 9 | ||||
| Page Range: | pp. 3611-3617 | ||||
| Date: | 2010 | ||||
| Additional Information (public): | CAN 152:516583 1-3 Pharmacology 9000-81-1 (Acetylcholinesterase); 9001-08-5 Role: BSU (Biological study, unclassified), BIOL (Biological study) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents); 103800-21-1P; 1225056-56-3P; 1225056-70-1P; 1225056-71-2P; 1225056-72-3P; 1225056-73-4P; 1225056-74-5P; 1225056-75-6P Role: PAC (Pharmacological activity), RCT (Reactant), SPN (Synthetic preparation), THU (Therapeutic use), BIOL (Biological study), PREP (Preparation), USES (Uses), RACT (Reactant or reagent) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents); 244-63-3 (9H-Pyrido[3,4-b]indole); 30684-42-5; 58982-28-8 (9H-Pyrido[3,4-b]indol-6-ol) Role: PAC (Pharmacological activity), RCT (Reactant), THU (Therapeutic use), BIOL (Biological study), USES (Uses), RACT (Reactant or reagent) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents); 5667-11-8P; 53952-75-3P; 950993-91-6P; 1225056-47-2P; 1225056-48-3P; 1225056-49-4P; 1225056-50-7P; 1225056-51-8P; 1225056-52-9P; 1225056-53-0P; 1225056-54-1P; 1225056-55-2P; 1225056-57-4P; 1225056-58-5P; 1225056-59-6P; 1225056-60-9P; 1225056-61-0P; 1225056-62-1P; 1225056-63-2P; 1225056-64-3P; 1225056-65-4P; 1225056-68-7P; 1225056-69-8P; 1225056-76-7P Role: PAC (Pharmacological activity), SPN (Synthetic preparation), THU (Therapeutic use), BIOL (Biological study), PREP (Preparation), USES (Uses) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents); 7212-59-1; 16502-01-5 (1,2,3,4-Tetrahydro-beta -carboline); 20315-68-8 (6-Methoxy-1,2,3,4-Tetrahydro-beta -carboline); 30684-43-6; 59444-69-8 Role: PAC (Pharmacological activity), THU (Therapeutic use), BIOL (Biological study), USES (Uses) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents); 74-88-4 (Methyl iodide); 110-52-1; 110-86-1 (Pyridine); 111-24-0; 112-60-7; 623-24-5; 629-03-8 (1,6-Dibromohexane); 629-27-6; 3344-70-5; 4101-68-2; 4549-31-9; 4549-32-0; 4549-33-1; 16696-65-4; 746549-76-8 Role: RCT (Reactant), RACT (Reactant or reagent) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents); 31255-26-2P; 1225056-66-5P; 1225056-67-6P Role: RCT (Reactant), SPN (Synthetic preparation), PREP (Preparation), RACT (Reactant or reagent) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents) | ||||
| Institutions: | Chemistry and Pharmacy > Institute of Pharmacy > Pharmaceutical Biology (Prof. Heilmann) | ||||
| Identification Number: |
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| Keywords: | Alzheimer disease Cognitive disorders Enzyme inhibitors NMDA receptor antagonists Neurodegenerative disease Structure-activity relationship (bivalent beta -carbolines as potential multitarget anti-alzheimer agents) NMDA receptors Role: BSU (Biological study, unclassified), BIOL (Biological study) (bivalent beta -carbolines as potential multitarget anti-alzheimer agents) Toxins Role: BSU (Biological study, unclassified), BIOL (Biological study) (excitotoxins bivalent beta -carbolines as potential multitarget anti-alzheimer agents) acetylcholinesterase inhibitor NMDA Alzheimers disease carboline deriv SAR prepn | ||||
| Dewey Decimal Classification: | 500 Science > 570 Life sciences 500 Science > 540 Chemistry & allied sciences | ||||
| Status: | Published | ||||
| Refereed: | Yes, this version has been refereed | ||||
| Created at the University of Regensburg: | Yes | ||||
| Item ID: | 17255 |
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 ...
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 redn. of pathol. 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 compds. 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 compd. was a N9-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 micro M for NR, resp.
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