66549-15-3Relevant articles and documents
Synthesis and Structure-Activity Relationships of Series of Aminopyridazine Derivatives of γ-Aminobutyric Acid Acting as Selective GABA-A Antagonists
Wermuth, Camille-Georges,Bourguignon, Jean-Jacques,Schlewer, Gilbert,Gies, Jean-Pierre,Schoenfelder, Angele,et al.
, p. 239 - 249 (2007/10/02)
We have recently shown that an aryloaminopyridazine derivarive of GABA, SR 95103 , is a selective and competitive GABA-A receptor antagonist.In order to further explore the structural requirements for GABA receptor affinity, we synthesized a series of 38 compounds by attaching various pyridazinic structures to GABA or GABA-like side chains.Most of the compounds displaced GABA from rat brain membranes.All the active compounds antagonized the GABA-elicited enhancement of diazepam binding, strongly suggesting that all these compounds are GABA-A receptor antagonists.None of the compounds that displaced GABA from rat brain membranes interacted with other GABA recognition sites (GABA-B receptor, GABA uptake binding site, glutamate decarboxylase, GABA-transaminase).They did not interact with the Cl- ionophore associated with the GABA-A receptor and did not interact with the benzodiazepine, strychnine, and glutamate binding sites.Thus these compounds appear to be specific GABA-A receptor antagonists.In terms of structure-activity, it can be concluded that a GABA moiety bearing a positive charge is necessary for optimal GABA-A receptor recognition.Additional binding sites are tolerated only if they are part of a charge-delocalized amidinic or guanidinic system.If this delocalization is achieved by linking a butyric acid moiety to the N(2) nitrogen of a 3-aminopyridazine, GABA-antagonistic character is produced.The highest potency (ca.250 times bicuculline) was observed when an aromatic ? system, bearing electron-donating substituents, was present on the 6-position of the pyridazine ring.
Pyridazine and pyrimidine compounds active on the central nervous system as sedatives or anticonvulsants
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, (2008/06/13)
The present invention relates to the compounds of formula STR1 in which X1 represents N or STR2 X2 represents N or STR3 provided that X1 and X2 are different from each other; R1 and R2 bein
6-Phenyl-1,2,4-triazolo[4,3-b]pyridazine hypotensive agents
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, (2008/06/13)
This disclosure describes novel substituted 6-phenyl-1,2,4-triazolo[4,3-b]pyridazines useful as hypotensive agents.
