Synthesis and structure-activity relationships of a series of aminopyridazine derivatives of γ-aminobutyric acid acting as selective GABA-A antagonists was written by Wermuth, Camille Georges;Bourguignon, Jean Jacques;Schlewer, Gilbert;Gies, Jean Pierre;Schoenfelder, Angele;Melikian, Anita;Bouchet, Marie Jeanne;Chantreux, Dominique;Molimard, Jean Charles. And the article was included in Journal of Medicinal Chemistry in 1987.Quality Control of 5-Phenylpyridazin-3-amine The following contents are mentioned in the article:
Thirty-eight title compounds, e.g., I, were prepared by attaching various pyridazinic structures to GABA or GABA-like side chains. Thus, aminopyridazine II was treated with BrCH2CH2CO2Et, followed by K2CO3 and then HCl-AcOH to give I. Most of the compounds displaced [3H]GABA from rat brain membranes. All the active compounds antagonized the GABA-elicited enhancement of [3H]diazepam binding, strongly suggesting that all these compounds are GABA-A receptor antagonists. None of the compounds that displaced [3H]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 is concluded that a GABA moiety bearing a pos. charge is necessary for optimal GABA-A receptor recognition. Addnl. 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 (≃250 times bicuculline) was observed when an aromatic π system, bearing electron-donating substituents, was present on the 6-position of the pyridazine ring. This study involved multiple reactions and reactants, such as 5-Phenylpyridazin-3-amine (cas: 105537-97-1Quality Control of 5-Phenylpyridazin-3-amine).
5-Phenylpyridazin-3-amine (cas: 105537-97-1) belongs to pyridazine derivatives. Pyridazines is a six-membered nitrogen-containing significant heterocycle. It has received considerable interest because of its useful applications as natural products, pharmaceuticals, and various bioactive molecules. Specifically, the pyridazine moiety is an important structural feature of various pharmacologically important compounds with activities like antimicrobial, analgesic, anti-inflammatory, antiplatelet, anticancer, antisecretory, antiulcer, antidepressant, cardiotonic, vasodilator, antiarrhythmic, and hypocholesterolaemic.Quality Control of 5-Phenylpyridazin-3-amine
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem