Synthesis and preliminary evaluation activity studies of novel 4-(aryl/heteroaryl-2-ylmethyl)-6-phenyl-2-[3-(4-substituted-piperazine-1-yl)propyl]pyridazin-3(2H)-one derivatives as anticancer agents

Murty, M. S. R.; Rao, B. Ramalingeswara; Ram, Kesur R.; Yadav, J. S.; Antony, Jayesh; Anto, Ruby John

doi:10.1007/s00044-011-9851-6

Cited by 20 publications

(5 citation statements)

References 18 publications

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“…Pyridazine-based frameworks are widely distributed in biologically active products with anti-viral [ 15 , 16 , 17 , 18 , 19 , 20 ], anti-inflammatory [ 21 , 22 , 23 , 24 , 25 ], anti-microbial [ 26 , 27 , 28 ], anti-cancer [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ], anti-convulsant [ 37 , 38 , 39 , 40 ], anti-analgesic [ 41 , 42 ], anti-tubercular [ 43 , 44 , 45 ], anti-hypertensive [ 3 , 46 ], anti-diabetic [ 47 ], anti-depressant [ 48 , 49 ], anti-Alzheimer’s [ 50 , 51 ], phosphodiesterase [ 52 , 53 ], platelet aggregation [ 54 , 55 , 56 , 57 ], and cholesterol acyl transferase inhibitor properties [ 58 ]. Peptide nucleic acids (PNAs) with new pyridazine-type nucleobases were reported as replacements for the DNA duplex bases instead of thymine, adenine, guanine and cytosine to form novel DNA or RNA duplexes [ 59 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation

et al. 2017

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4-(2-(4-Halophenyl)hydrazinyl)-6-phenylpyridazin-3(2H)-ones 1a,b were prepared and treated with phosphorus oxychloride, phosphorus pentasulphide and ethyl chloroformate to give the corresponding chloropyridazine, pyridazinethione, oxazolopyridazine derivatives 2–4, respectively. Compound 2 reacted with hydrazine hydrate to afford hydrazinylpyridazine 7. The reaction of 4-(2-(4-chlorophenyl)hydrazinyl)-3-hydrazinyl-6-phenylpyridazine (7) with acetic anhydride, p-chlorobenzaldehyde and carbon disulphide gave the corresponding pyridazinotriazine derivatives 8–10. On the other hand, 5-(4-chlorophenylamino)-7-(3,5-dimethoxybenzylidene)-3-phenyl-5H-pyridazino[3,4-b][1,4]thiazin-6(7H)-one (11) was prepared directly from the reaction of compound 3 with chloroacetic acid in presence of p-chlorobenzaldehyde. Compound 11 reacted with nitrogen nucleophiles (hydroxylamine hydrochloride, hydrazine hydrate) and active methylene group-containing reagents (malononitrile, ethyl cyanoacetate) to afford the corresponding fused compounds 12–15, respectively. Pharmacological screening for antiviral activity against hepatitis A virus (HAV) was performed for the new compounds. 4-(4-Chlorophenylamino)-6-phenyl-1,2-dihydropyridazino[4,3-e][1,2,4]triazine-3(4H)-thione (10) showed the highest effect against HAV.

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Section: Introductionmentioning

confidence: 99%

Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation

et al. 2017

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“…20 Recently, as part of our on-going programme to discover and develop potential new anticancer agents, we have been reported alkyl chain arylpiperazine containing heterocyclic hybrids that includes benzoxazole/benzothiazole, triazoles and oxadiazoles moieties. 21,22 Thus, in continuation of our lasting interest in chemistry and pharmacological properties of tetrazole and substituted arylpiperazine, we incorporated the structural features of 5-thio substituted tetrazole and along with alkyl chain arylpiperazine by well-known using molecular hybridization approach 23,24 for drug like molecules build-up, which allows achieving new pharmacological profile. Furthermore, after widespread literature search, it was observed that, till date no effort has been made to combine these vital moieties as a single molecular scaffold.…”

Section: Figure 1 Some Of the Important Bioactive Tetrazole Compoundsmentioning

confidence: 99%

Regioselective synthesis and preliminary cytotoxic activity properties of tetrazole appendage N-substituted piperazine derivatives

Dileep¹,

Katiki²,

Rao³

et al. 2017

Org. Commun.

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A series of 1-(4-substituted)-4-(3-((1-(substituted)-1H-tetrazol-5-yl)thio)propyl)piperazine derivatives were (6a-t) synthesized by KF-Al 2 O 3 mediated S-alkylation of 5-thio-substituted tetrazole with 1-(3-chloropropyl)-4-(4-substituted)piperazine. The structures of the newly synthesized compounds were characterized by NMR and MS spectral data. Further, the regioselective formation of C-S bond was unambiguously confirmed by single crystal Xray diffraction. All the synthesized compounds were screened for their in vitro cytotoxic activities against two cancer cell lines: DU-145 (prostate cancer) and HeLa (cervical cancer). These cell lines were utilized in MTT assays and the obtained results were compared to doxorubicin, and their IC 50 values were determined. Among the compounds tested, 6f, 6j, 6m, 6n, 6o, 6q, 6r and 6t showed considerable potent activity, while the compound 6p exhibited significant potent activity against DU-145 and HeLa cancer cell lines compare to standard Doxorubicin.

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“…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). In addition, pyridazinones act as core nucleus in various drugs e.g.…”

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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Synthesis and preliminary evaluation activity studies of novel 4-(aryl/heteroaryl-2-ylmethyl)-6-phenyl-2-[3-(4-substituted-piperazine-1-yl)propyl]pyridazin-3(2H)-one derivatives as anticancer agents

Cited by 20 publications

References 18 publications

Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation

Synthesis of Some New Pyridazine Derivatives for Anti-HAV Evaluation

Regioselective synthesis and preliminary cytotoxic activity properties of tetrazole appendage N-substituted piperazine derivatives

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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