Synthesis of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5h )-triones as NMDA glycine-site antagonists

Synthesis of 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5h )-triones as NMDA glycine-site antagonists

Several members of the 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones (2) have been identified as being potent and selective NMDA glycine-site antagonists. Increasing size of the alkyl substituent on the alpha-carbon led to a progressive decrease in binding...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2003-10, Vol.13 (20), p.3553-3556
Hauptverfasser: BROWN, Dean G, URBANEK, Rebecca A, XIAO, Wenhua, DYROFF, Martin C, LEE, Chi-Ming C, TRIVEDI, Shephali, NEILSON, Kathy L, KEITH, Richard A, BARE, Thomas M, MCLAREN, Frances M, HORCHLER, Carey L, MURPHY, Megan, STEELMAN, Gary B, EMPFIELD, James R, FORST, Janet M, HERZOG, Keith J
Format: Artikel
Sprache:eng
Schlagworte:
Biological and medical sciences
Glutamatergic system (aspartate and other excitatory aminoacids)
Glycine - chemistry
Medical sciences
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Pyridazines - chemical synthesis
Pyridazines - chemistry
Pyridazines - pharmacology
Quinolines - chemical synthesis
Quinolines - chemistry
Quinolines - pharmacology
Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors
Receptors, N-Methyl-D-Aspartate - chemistry
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Zusammenfassung:Several members of the 7-chloro-2,3-dihydro-2-[1-(pyridinyl)alkyl]-pyridazino[4,5-b]quinoline-1,4,10(5H)-triones (2) have been identified as being potent and selective NMDA glycine-site antagonists. Increasing size of the alkyl substituent on the alpha-carbon led to a progressive decrease in binding affinity. Some of these analogues possess improved drug-like properties such as cellular permeability, solubility and oral absorption.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(03)00750-9