4776-87-8

Usage

Uses

Used in Pharmaceutical Industry:
3-AMINO-6-(4-METHOXYPHENYL)PYRIDAZINE is used as a selective GABA-A antagonist for its ability to block the GABA-A receptors, which play a crucial role in the central nervous system. This antagonistic property makes it a valuable compound in the development of drugs aimed at treating various neurological disorders and conditions related to the GABA-A receptor system.
Used as an Intermediate in Drug Synthesis:
3-AMINO-6-(4-METHOXYPHENYL)PYRIDAZINE serves as an intermediate in the synthesis of the drug Gabazine, which is a GABA-A receptor antagonist used in the treatment of certain neurological conditions. Its role as an intermediate is essential in the production process of this specific drug, highlighting its importance in the pharmaceutical sector.

Biological Activity

6-(4-methoxyphenyl)-3-pyridazinamine is a gabaa receptor antagonist.ionotropic gabaa receptors are ligand-gated ion channels that facilitate the passing of chloride ions across the cell membrane and promote an inhibitory influence on target neurons. these receptors are the major targets for benzodiazepines and related anxiolytic drugs.

in vitro

6-(4-methoxyphenyl)-3-pyridazinamine is an intermediate in the synthesis of sr 95103 [2-(3-carboxypropyl)-3-amino-4-methyl-6-phenylpyridazinium chloride]. sr 95103 was identified as a selective and competitive gaba-a receptor antagonist. moreover, sr 95103 was shown to be able to displace [3h]gaba from rat brain membranes with an apparent ki of 2.2 μm. in addition, sr 95103 was found, on the basis of biochemical, electrophysiological, and pharmacological results, to be a selective and competitive antagonist of gaba at the gaba-a receptor site [1].

in vivo

the behavioral effects of unilateral microinjections of sr 95103 into periventricular structures were studied. results showed that when injected into the medial hypothalamus (mh) or into the dorsal part of the mesencephalic central gray (cg), sr 95103 produced a dose-dependent behavioral activation together with jumps. the behavioral activation was found to be attenuated by pretreatment with thip, a gaba receptor agonist [2].

references

[1] wermuth, c. g.,bourguignon, j.j.,schlewer, g., et al. synthesis and structure-activity relationships of a series of aminopyridazine derivatives of γ-aminobutyric acid acting as selective gaba-a antagonists. journal of medicinal chemistry 30(2), 239-249 (1987).[2] schmitt p, di scala g, brandao ml, karli p. behavioral effects of microinjections of sr 95103, a new gaba-a antagonist, into the medial hypothalamus or the mesencephalic central gray. eur j pharmacol. 1985 nov 5;117(2):149-58.

InChI:InChI=1/C10H8ClN3OS2/c1-16-10-14-13-9(17-10)12-8(15)6-2-4-7(11)5-3-6/h2-5H,1H3,(H,12,13,15)

Upstream product

• 18772-76-4 3-hydrazino-6-(p-methoxyphenyl)pyridazine 
• 5469-69-2 6-chloro-pyridazin-3-ylamine 
• 5720-07-0 4-methoxyphenylboronic acid 
• 187973-60-0 6-iodopyridazine-3-amine 
• 58059-31-7 3-chloro-6-(4-methoxyphenyl)pyridazine 
• 2166-33-8 6-(4-methoxyphenyl)-2H-pyridazin-3-one 

Downstream Products

• 105538-31-6 6-Amino-1-(3-ethoxycarbonyl-propyl)-3-(4-methoxy-phenyl)-pyridazin-1-ium; bromide 
• 1150567-81-9 N'-[6-(4-methoxy-benzyl)-pyridazin-3-yl]-N,N-dimethyl-formamidine 
• 1244590-99-5 BrH*C₁₅H₁₉N₃O 
• 1244590-90-6 C₁₇H₂₁N₃O₃*ClH 
• 1244590-93-9 BrH*C₁₆H₁₉N₃O₃ 
• 105538-31-6 ethyl 4-[6-imino-3-(4-methoxyphenyl)pyridazin-1-yl]butanoic acid hydrobromide 
• 1244590-95-1 BrH*C₁₈H₂₃N₃O₃ 
• 1244590-97-3 BrH*C₁₈H₂₆N₃O₄P 
• 113278-16-3 SR 95813 
• 1244591-00-1 BrH*C₁₄H₁₇N₃O₂ 
• 763886-63-1 3-aminopyridazine 
• 1629613-17-7 7-(4-methoxyphenyl)-4-(trifluoromethyl)-2H-pyrimido[1,2-b]pyridazin-2-one 
• 104104-50-9 2-(3-carboxypropyl)-3-amino-6-(4-methoxyphenyl)pyridazinium bromide 
• 170165-28-3 [6-(4-Methoxy-phenyl)-imidazo[1,2-b]pyridazin-3-yl]-phenyl-acetic acid ethyl ester 

Relevant academic research and scientific papers

Discovery of 2-(Imidazo[1,2- b]pyridazin-2-yl)acetic Acid as a New Class of Ligands Selective for the γ-Hydroxybutyric Acid (GHB) High-Affinity Binding Sites

Gabazine, a γ-aminobutyric acid type A (GABAA) receptor antagonist, has previously been reported to inhibit the binding of [3H]NCS-382, a representative ligand of the high-affinity binding site for the neuroactive substance γ-hydroxy

Design and synthesis of some new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring and the investigation of their inhibitory potential on in-vitro acetylcholinesterase and butyrylcholinesterase

A series of new carboxamide and propanamide derivatives bearing phenylpyridazine as a core ring were designed, synthesized and evaluated for their ability to inhibit both cholinesterase enzymes. In addition, a series of carboxamide and propanamide derivat

COMPOUNDS FOR MODULATING AQUAPORINS

The invention relates to compounds of formula (I) pharmaceutical compositions thereof and methods for modulating aquaporin 9.

Mild and direct access to 7-substituted-4-trifluoromethylpyrimido[1,2- b ]pyridazin-2-one systems

New and efficient methods for the synthesis of 7-substituted-4- trifluoromethylpyrimido[1,2-b]pyridazin-2-one derivatives using either two-step Suzuki/heterocyclization, or two-step heterocyclization/substitution sequences are developed. A variety of substituted products are obtained in good to excellent yields from 3-amino-6-chloropyridazine and ethyl 4,4,4-trifluorobut-2- ynoate. Georg Thieme Verlag Stuttgart · New York.

Competitive antagonism of insect GABA receptors by iminopyridazine derivatives of GABA

A series of 4-(6-imino-3-aryl/heteroarylpyridazin-1-yl)butanoic acids were synthesized and examined for antagonism of GABA receptors from three insect species. When tested against small brown planthopper GABA receptors, the 3,4-methylenedioxyphenyl and the 2-naphthyl analogues showed complete inhibition of GABA-induced fluorescence changes at 100 μM in assays using a membrane potential probe. Against common cutworm GABA receptors, these analogues displayed approximately 86% and complete inhibition of GABA-induced fluorescence changes at 100 μM, respectively. The 4-biphenyl and 4-phenoxyphenyl analogues showed moderate inhibition at 10 μM in these receptors, although the inhibition at 100 μM was not complete. Against American cockroach GABA receptors, the 4-biphenyl analogue exhibited the greatest inhibition (approximately 92%) of GABA-induced currents, when tested at 500 μM using a patch-clamp technique. The second most active analogue was the 2-naphthyl analogue with approximately 85% inhibition. The 3-thienyl analogue demonstrated competitive inhibition of cockroach GABA receptors. Homology modeling and ligand docking studies predicted that hydrophobic 3-substituents could interact with an accessory binding site at the orthosteric binding site.

Microwave-enhanced synthesis of 2,3,6-trisubstituted pyridazines: Application to four-step synthesis of gabazine (SR-95531)

Microwave-enhanced, highly efficient protocols for the synthesis of synthetically and biologically important 2,3,6-trisubstituted pyridazine architectures have been developed by sequential amination/Suzuki coupling/alkylation reactions. This powerful strategy is an economical and highly chemoselective protocol for the synthesis of diversified pyridazines. The total synthesis of gabazine (SR-95531) has been achieved using a versatile strategy in four steps and 73% overall yield.

IMIDAZOPYRIDAZINES FOR USE AS PROTEIN KINASE INHIBITORS

There is provided compounds of formula (I): wherein Z, M, R1, X, R3, R4 and R5 have meanings given in the description, an pharmaceutically-acceptable esters, amides, solvates or salts thereof, which compounds are useful in the treatment of diseases in which inhibition of a protei kinase (e.g. a PIM family kinase or PI3-K) is desired and/or required, an particularly in the treatment of cancer.

Efficient one-step synthesis of 3-amino-6-arylpyridazines

Starting from the commercially available 3-amino-6-chloropyridazine, 3-amino-6-arylpyridazines were prepared in good yields by means of a Suzuki cross-coupling reaction avoiding the somewhat lengthy four-step classic synthesis.

A new approach towards the synthesis of 3-amino-6- (hetero)arylpyridazines based on palladium catalyzed cross-coupling reactions

The synthesis of 3-amino-6-(hetero)arylpyridazines via palladium catalyzed cross-coupling reactions (Suzuki, Stille) on 3-amino-6- chloropyridazine (1a) and 3-amino-6-iodopyridazine (1b) has been investigated. Comparison of the results shows that there is