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 affinity. Some of these analogues possess improved drug-like properties such as cellular permeability, solubility and oral absorption.
D005998:Glycine / Q000737:chemistry*; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000737:chemistry
D011724:Pyridazines; D011804:Quinolines; D016194:Receptors, N-Methyl-D-Aspartate; D005998:Glycine