Anticonvulsant activity of 3-oxo-5-substituted benzylidene-6-methyl-(4H)-2-pyridazinylacetamides and 2-pyridazinylacetylhydrazides.

Rubat, Catherine; Coudert, Pascal; Refouvelet, Bernard; Tronche, P; Bastide, P; Bastide, J.

doi:10.1248/cpb.38.3009

Cited by 43 publications

(18 citation statements)

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“…The structure of the title compound determined by X-ray diffraction corroborates the aromatic structure of the pyridazine ring suggested by recent NMR spectroscopic data (Bebot, Coudert & Couquelet, unpublished work), contrary to former results (Rubat et al, 1990) describing a dihydro skeleton with a 5-arylidene moiety. (Prout et al, 1994)].…”

Section: Commentsupporting

confidence: 87%

“…The carbonyl O atom O(16) and the N(2)--H(2) amino group form an intermolecular hydrogen bond, the details of which are given in Table 2. tor (Villar et al, 1989;Brandau, Bourguignon & Wermuth, 1991) when they are substituted by an electronrich group, such as an acetamido side chain at N(2) (Rubat et al, 1990), or fused with a triazole ring (Moreau et al, 1994). …”

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confidence: 99%

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5-(2-Chlorobenzyl)-6-methyl-3(2H)-pyridazinone

Moreau¹,

Métin²,

Coudert³

et al. 1995

Acta Crystallogr C

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(Sheldrick, 1990) refined using a riding model with fixed isotropic displacement parameters (1.5Ueq of the parent atom).Structure solution: SHELXTL/PC (Sheldrick, 1990 Acta Cryst. (1995). C51, 1834-1836 5-(2-Chlorobenzyl)-6-methyl-3(2H)-pyridazinone Table 2. Selected geometric parameters (A, °) 01----c41.214 (6) c4---c5 1.480 (7) CommentThe structure determination of 5-( 2-chlorobenzyl )-6-methyl-3(2H)-pyridazinone was undertaken to confirm that 5-benzylpyridazine derivatives satisfy pharmacophore requirements (Villar et al., 1989;Brandau, Bourguignon & Wermuth, 1991) of central benzodiazepine receptors, as suggested by previous molecularmodelling studies (Moreau et al., 1994). Table 2). The carbonyl O atom O(16) and the N(2)--H(2) amino group form an intermolecular hydrogen bond, the details of which are given in Table 2. tor (Villar et al., 1989;Brandau, Bourguignon & Wermuth, 1991) when they are substituted by an electronrich group, such as an acetamido side chain at N(2) (Rubat et al., 1990), or fused with a triazole ring (Moreau et al., 1994). ExperimentalThe title compound was crystallized from ethanol after the reaction of levulinic acid with 2-chlorobenzaldehyde followed by condensation with hydrazine hydrate. The crystal density Om was measured by flotation in xylene. Crystal data1.500 (4) C (13) • .C (7 v) 3.551 (3) C(13).• .C(14 vii) 3.725 (6) C(4).• .CI(10 '~) 3.562 (3)121.6 (3) C ( Data reduction and other calculations were performed using MolEN (Fair, 1990). Lorentz and polarization corrections were applied to the data. The non-H atoms were located by direct methods using MULTAN11/82 (Main et al., 1982). Molecular graphics were produced using ORTEPII (Johnson, 1976 AbstractThe title compound, C9HlaN203 (alternative name:1-acetyl-3,4,6-trimethyl-2,5-piperazinedione), assumes a boat conformation with both methyl substituents in pseudo-axial orientations. The degree of folding of the diketopiperazine ring, defined by the angle between the planes containing the two endocyclic amide bonds, was found to be -29.1 °. CommentThe conformations of a number of diketopiperazines have been studied by X-ray diffraction (for examples and leading references, see Karle, 1981). In an attempt

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Section: Commentsupporting

confidence: 87%

mentioning

confidence: 99%

5-(2-Chlorobenzyl)-6-methyl-3(2H)-pyridazinone

Moreau¹,

Métin²,

Coudert³

et al. 1995

Acta Crystallogr C

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“…Infrared spectra were measured on Perkin-Elmer spectrophotometer Model 1430 using potassium bromide pellets and frequencies are reported in cm À1 . The 1 H-NMR and 13 C-NMR spectra were measured in DMSO-d 6 on Varian Genini-300 MHz spectrometer and chemical shifts, d are in ppm. The mass spectral (m/z) values were measured on an HP model GC MS-QPL000EX (Shimadzu) at 70-eV mass spectrometer.…”

Section: Chemistrymentioning

confidence: 99%

“…Pyridazine compounds have been reported to possess varied biological activities such as anti-HIV 1 , anti-TMV 2 , antidepressant 3 , antihypertensive 4 , antithrombotic 5 , anticonvulsant 6 , cardiotonic 7 , anti-bacterial 8 , diuretic 9 and anticancer 10 . Antibacterial, antifungal, antituberculosis, antiviral, anti-inflammatory, anticancer and effectiveness against cardiovascular disorders have also been reported 11,12 .…”

Section: Introductionmentioning

confidence: 99%

New pyrano[2,3-c]pyridazine derivatives with antimicrobial activity synthesized using piperidine as the organocatalyst

Kandile

Zaky

2014

Journal of Enzyme Inhibition and Medicinal Chemistry

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A simple and efficient method for the synthesis of highly diverse pyrano [2,3-c]pyridazines was achieved by a one pot multicomponent reaction using piperidine as the organocatalyst. The synthesis of a series of heterocyclic derivatives with varying functionality (e.g. thiazine, tetrazole and pyrimidine) incorporating the pyrano[2,3-c]pyridazine moiety were achieved via reaction of 2a-e with different reagents. The structures of the synthesized derivatives were elucidated by FTIR, MS, 1 H and 13 C NMR spectroscopy. A number of the newly synthesized targeted compounds 2b-e, 3a-c and 4a-c were evaluated for their in vitro antibacterial activity and were compared with chloramphenicol and nystatin as broad spectrum reference standard antibiotics. Tests were carried out against Staphylococcus aureus (MTCC3160) and Enterococcusi fecalis as Gram-positive bacteria, and Escherichia coli (MTCC1652) and Klebsiella pneumonia as Gram-negative bacteria. Antifungal potential against Candida albicans, and Aspergillus albicans strains were also evaluated. The results revealed that compounds 3a and 3c showed strong significant activity relative to the reference against these bacterial and fungal strains.

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“…In recent years, synthesis of novel pyridazinone derivatives and investigation of their chemical and biological behavior have gained more importance due to their biological, medicinal, and agricultural reason. This privileged structure attracts the interest of medicinal chemists as a nucleus of potential therapeutic utility and exhibits several pharmacological activities such as analgesic (Asif, et al, 2011), anti-inflammatory (Gokce, et al, 2009), antidepressant (Coelho, et al, 2003), antihypertensive (Demirayak, et al, 2004), anticonvulsant (Rubat, et al, 1990), cardiotonic (Amin, et al, 2010), diuretic (Akahane, et al, 1999), and anti-HIV (Livermone, et al, 1993) activities. Certain pyridazinone derivatives containing the 2-phenyl-indolyl moiety have also shown anti-cancer activity (Murty, et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Computer Aided Screening and Pharmacological Evaluation of 2/3-Substituted-6(4-Methylphenyl)-4,5-Dihydropyridazin3(2h)-Ones, and Pyridazine Substituted Triazine

Husain

Khokra

Seth

et al. 2017

Indonesian J. Pharm.

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The present research work involved synthesis of some new pyridazine derivatives and evaluation of their analgesic and antiinflammatory activities in experimental animals to obtain safer non-steroidal anti-inflammatory agents (NSAIDs). Friedel-Crafts acylation reaction of succinic anhydride with toluene in the presence of anhydrous aluminum chloride gave 4-(4-methylphenyl)-4-oxo-butanoic acid (1). The aryl propionic acid 1 on reaction with phenyl hydrazine and hydrazine hydrate yielded the pyridazinone derivative 2 and 3, respectively. Reaction of the compound 3 with phosphorus oxychloride (POCl 3 ) produced the corresponding chloropyridazine derivative 4. A 4-hydroxymethyl derivative of dihydropyridazinone (5) was synthesized by condensing 3 with methanol and formaldehyde (HCHO). The compound 5 on further treatment with guanidine hydrochloride in ethanol gave the pyridazino-triazine (6). The synthesized compounds were investigated for their analgesic activity in mice and anti-inflammatory activity in Wistar albino rats. The molecular, pharmacokinetic and toxicity properties of the synthesized compounds were calculated by Molinspiration and Osiris property explorer software. The results of in-vivo antiinflammatory studies revealed that the compound. 4 showed maximum inhibition in paw edema volume followed by compound 3 while the compound 4 exhibited excellent peripheral analgesic activity (74%) followed by the compound 5. Compound s 4 and 5 also showed good central analgesic effect increased the reaction time to 90 minutes. All the title compounds except compound 5 are predicted to be safe by Osiris online software and are likely to have good oral bioavailability as they obey Lipinski's rule of five for drug likeness.

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Anticonvulsant activity of 3-oxo-5-substituted benzylidene-6-methyl-(4H)-2-pyridazinylacetamides and 2-pyridazinylacetylhydrazides.

Cited by 43 publications

References 1 publication

5-(2-Chlorobenzyl)-6-methyl-3(2H)-pyridazinone

5-(2-Chlorobenzyl)-6-methyl-3(2H)-pyridazinone

New pyrano[2,3-c]pyridazine derivatives with antimicrobial activity synthesized using piperidine as the organocatalyst

Synthesis, Computer Aided Screening and Pharmacological Evaluation of 2/3-Substituted-6(4-Methylphenyl)-4,5-Dihydropyridazin3(2h)-Ones, and Pyridazine Substituted Triazine

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