1079-73-8Relevant academic research and scientific papers
Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
, (2020/04/07)
Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
A new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studies
?z?elik, Azime Berna,?zdemir, Zeynep,Sari, Suat,Utku, Semra,Uysal, Mehtap
, p. 1253 - 1263 (2019/11/03)
Background: The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of cholinesterases is an effective method to curb Alzheimer's disease. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer's Disease. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach. Method: We obtained our compounds by the reaction of various substituted/nonsubstituted benzenesulfonic acid derivatives with 6-substitutedphenyl-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman's method. Molecular docking studies were done using Glide and the results were evaluated on Maestro (Schr?dinger, LLC, New York, NY, 2019). Results: The title compounds showed moderate inhibition at 100 μg/ml against both enzymes, yet with better activity against BChE. Compound VI2a emerged as a dual inhibitor with 25.02% and 51.70% inhibition against AChE and BChE, respectively. Conclusion: This study supports that novel pyridazinone derivates may be used for the development of new BChE inhibitory agents. It was less potent than the reference drugs, yet promising for further modifications as a lead. The ability of the compounds to adopt energetically more favourable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE.
Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
Partap, Sangh,Yar, Mohammad Shahar,Hassan, Md. Zaheen,Akhtar, Md. Jawaid,Siddiqui, Anees A.
, (2017/10/06)
A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABAA receptor.
Synthesis and anti-tubercular activity of 6-(4-chloro/methyl-phenyl)-4-arylidene-4,5-dihydropyridazin-3(2H)-one derivatives against Mycobacterium tuberculosis
Asif, Mohammad,Singh, Anita
, p. 500 - 504 (2015/06/22)
Two series of 6-(4-Cl-Phenyl)-4-arylidene-4,5-dihydropyridazin-3(2H)-one (3a-e) and 6-(4-CH3-Phenyl)-4-arylidene-4,5-dihydropyridazin-3(2H)-one derivatives (3f-j) were synthesized and evaluated as antitubercular agents against Mycobacterium tuberculosis H37Rv strain by using Microplate Alamar Blue Assay (MABA) method. These compounds (3a-e & 3f-j) were synthesized from 6-(4-Cl-Phenyl)-4,5-dihydropyridazin-3(2H)-one (2a) and 6-(4-CH3-Phenyl)-4,5-dihydropyridazin-3(2H)-one (2b) compounds by reacting with appropriate aldehydes respectively. All title compounds (3a-e & 3f-j) were characterized on the basis of IR, 1HNMR, mass spectral and elemental analysis data. All title compounds (3a-e & 3f-j) were used at 0.2μg/mL to 100μg/mL dose levels for antitubercular activity. Result showed that all the title compounds (3a-e & 3f-j) exhibited less antitubercular activity as compared to the reference drugs streptomycin (MIC value of 6.25μg/mL) and pyrizinamide (MIC value of 3.125μg/mL), except compound 3e, which was equally effective as streptomycin but less effective than pyrazinamide.
Efficient synthesis, anticonvulsant and muscle relaxant activities of new 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6-phenyl-4,5-dihydropyridazin-3(2H) -one derivatives
Sharma, Bhawna,Verma, Amita,Sharma, Upendra Kumar,Prajapati, Sunil
, p. 146 - 157 (2014/03/21)
A series of 2-(2-(3-(4-chlorophenyl)-6-oxo-5,6-dihydropyridazin-1(4H)yl) acetyl)hydrazine carbothioamide and 2-((5-amino-1,3,4-thiadiazol-2-yl)methyl)-6- (4-chlorophenyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized, characterized, and evaluated for anticonvulsant activity and muscle relaxant activity. The synthesized compounds 5d (82.75 %) and 5e (85.44 %) showed promising anticonvulsant activity by protection against tonic hind limb extensor phase in maximal electroshock model (MES) at (50 mg/kg) compared to standard drug phenytoin and also compounds 5d (82.75 %), and 5e (85.44 %) showed significant anticonvulsant activity by protection against pentylenetetrazole- induced generalized convulsions in pentylenetetrazole model (PTZ) at (100 mg/kg) compared to standard drug diazepam. On the other hand, compound 5e showed significant muscle relaxant activity (84.57 %) by rotarod and traction test model comparing with diazepam as a standard drug.
Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives
Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd.,Goda, Chirag
, p. 552 - 559 (2015/02/19)
Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.
Further studies on 2-arylacetamide pyridazin-3(2H)-ones: Design, synthesis and evaluation of 4,6-disubstituted analogs as formyl peptide receptors (FPRs) agonists
Giovannoni, Maria Paola,Schepetkin, Igor A.,Cilibrizzi, Agostino,Crocetti, Letizia,Khlebnikov, Andrei I.,Dahlgren, Claes,Graziano, Alessia,Dal Piaz, Vittorio,Kirpotina, Liliya N.,Zerbinati, Serena,Vergelli, Claudia,Quinn, Mark T.
, p. 512 - 528 (2013/07/27)
Formyl peptide receptors (FPRs) play an essential role in the regulation of endogenous inflammation and immunity. In the present studies, a large series of pyridazin-3(2H)-one derivatives bearing an arylacetamide chain at position 2 was synthesized and te
Design, synthesis and antihypertensive screening of novel pyridazine substituted s-triazin-2-imine/one/thione derivatives
Mishra, Ravinesh,Siddiqui, Anees A.,Husain, Asif,Rashid, Mohd.,Goda, Chirag
, p. 552 - 559 (2013/05/08)
Some new 7-substituted-phenyl-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3, 5]triazin-2-imine/one/thione derivatives were synthesized by a sequence of reactions starting from appropriate aryl hydrocarbons. The final compounds were screened for antihypertensive activities by non-invasive method using Tail Cuff method. All the test compounds showed significant antihypertensive activity; 7-(biphenyl-4-yl)-3,4,8,9-tetrahydro-2H-pyridazino[1,6-a][1,3,5]triazin-2-imine (4p) exhibited antihypertensive activity more than the reference standard drugs.
Synthesis, characterization and antihypertensive activity of pyridazinone derivatives
Siddiqui, Anees A.,Mishra, Ravinesh,Shaharyar, Mohammad
scheme or table, p. 2283 - 2290 (2010/07/05)
Some 6-(substituted-phenyl)-2-(substitutedmethyl)-4,5-dihydropyridazin-3(2H)-one derivatives were synthesized by reacting 6-substituted-phenyl-4,5-dihydropyridazin-3(2H)-one with cyclic secondary amine under Mannich reaction conditions. The final compounds (15-70) were evaluated for antihypertensive activities by non-invasive method using Tail Cuff method. The compounds 16, 19, 24, 30, 39, 42 and 45 showed good antihypertensive activity.
