Derivatives of pyrrolo[3,4-d]pyridazinone, a new class of analgesic agents

Malinka, Wiesław; Redzicka, Aleksandra; Jastrzębska-Więsek, Magdalena; Filipek, Barbara; Dybała, Małgorzata; Karczmarzyk, Zbigniew; Urbańczyk‐Lipkowska, Zofia; Kalicki, Przemysław

doi:10.1016/j.ejmech.2011.08.006

Cited by 34 publications

(18 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The synthesis of all investigated compounds was performed according to the protocols published previously [24][25][26] and is presented in Figure 2. Analytical and spectroscopic properties of all newly obtained derivatives were in good agreement with their predicted features.…”

Section: Chemistrymentioning

confidence: 99%

“…The characteristic signal in the 1 H NMR spectrum near δ 4.98-5.10 ppm and the peak at around δ 70.01-70.42 ppm in the 13 C NMR spectrum indicate the presence of the methylene link that is typical for Mannich bases. According to many studies, the presence of an arylpiperazinyl or arylpiperidinyl group can significantly potentiate the analgesic activity of compound [19,[26][27][28][29]. Thereby, in our investigations, different amines were deliberately chosen to evaluate the influence of this pharmacophore on biological activity.…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

Effect of Novel Pyrrolo[3,4-d]pyridazinone Derivatives on Lipopolysaccharide-Induced Neuroinflammation

Wakulik

Wiatrak

Szczukowski

et al. 2020

IJMS

View full text Add to dashboard Cite

Neuroinflammation is considered to be one of the potential causes for the development of neurodegenerative diseases, including Alzheimer's disease. In this study, we evaluated the effect of four newly synthesized pyrrolo [3,4-d]pyridazinone derivatives on the neuron-like PC12 cells under simulated inflammation conditions by preincubation with lipopolysaccharide (LPS). Our novel derivatives are selective cyclooxygenase-2 (COX-2) inhibitors and have similar effects to nonsteroidal anti-inflammatory drugs (NSAIDs). We assessed viability (LDH assay), metabolic activity (MTT assay), DNA damage (number of double-strand breaks measured by fast halo assay), and the neuronal features of cells (average neurite length and neurite outgrowth measured spectrofluorimetrically). DCF-DA and Griess assays were also performed, which allowed determining the impact of the tested compounds on the level of oxygen free radicals and nitrites. LPS administration significantly negatively affected the results in all tests performed, and treatment with the tested derivatives in most cases significantly reduced this negative impact. Multiple-criteria decision analysis indicated that overall, the best results were observed for compounds 2a and 2b at a concentration of 10 µM. The new derivatives showed intense activity against free oxygen radicals and nitrites. Reduced reactive oxygen species level also correlated with a decrease in the number of DNA damage. The compounds improved neuronal features, such as neurite length and outgrowth, and they also increased cell viability and mitochondrial activity. Our results suggest that derivatives 2a and 2b may also act additionally on mechanisms other than 3a and 3b.

show abstract

Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Effect of Novel Pyrrolo[3,4-d]pyridazinone Derivatives on Lipopolysaccharide-Induced Neuroinflammation

Wakulik

Wiatrak

Szczukowski

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…The acute toxicity of the pyrrolopyridazinones were also studied and non-toxic effect was observed at the 2000 mg/kg (1420 mg/kg) i.p. dose level (Malinka at al., 2011).…”

Section: Biological Activitiesmentioning

confidence: 99%

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

Int¹

2019

Preprint

View full text Add to dashboard Cite

A series of heterocyclic compounds incorporating pyridazine moiety were for diverse biological activities. Pyridazines and pyridazinones derivatives showed wide spectrum of biological activities such as vasodialator, cardiotonic, anticonvulsant, antihypertensive, antimicrobial, anti-inflammatory, analgesic, anti-feedant, herbicidal, and various other biological, agrochemical and industrial chemical activities. The results illustrated that the synthesized pyridazine/pyridazine compounds have diverse and significant biological activities. Mechanistic insights into the biological properties of pyridazinone derivatives and various synthetic techniques used for their synthesis are also described.

show abstract

“…[1524][1525][1526][1527][1528] Article can be accessed online on: www.ijpsr.com Considerable interest has been attracted towards the pyridazine-3-one scaffold and its derivatives due to their widespread applications such as anticonvulsant activity 1 , antimicrobial activity 2 , antiviral activity 3 , anticancer 4 and analgesic activity 5 .…”

Section: Quick Response Code Doimentioning

confidence: 99%

Untitled

2013

IJPSR

View full text Add to dashboard Cite

Derivatives of pyrrolo[3,4-d]pyridazinone, a new class of analgesic agents

Cited by 34 publications

References 16 publications

Effect of Novel Pyrrolo[3,4-d]pyridazinone Derivatives on Lipopolysaccharide-Induced Neuroinflammation

Effect of Novel Pyrrolo[3,4-d]pyridazinone Derivatives on Lipopolysaccharide-Induced Neuroinflammation

Diverse chemical and biological potentials of various pyridazine and pyridazinone derivatives

Untitled

Contact Info

Product

Resources

About