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Synthesis and antidepressant activity of 5-(benzo[b]furan-2-ylmethyl)-6-methylpyridazin-3(2H)-one derivatives

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Abstract

A new series of pyridazin-3-one derivatives were designed, synthesized and evaluated for their preclinical antidepressant effect on Swiss mice. Among the series, compounds 6c, 6d and 6f exhibited significant activity profile in forced swimming test. Compounds 6c and 6d were most efficacious, which at dose of 50 mg kg−1 reduced the time of immobility by 42.85 and 38.09 %, respectively, as compared to the standard drug fluoxetine which reduced the immobility time by 45.23 % at the dose of 32 mg kg−1. All the test and standard compounds were administered orally 60 min before the test. Interestingly, all active compounds did not cause any significant alteration of locomotor activity in mice as compared to control, indicating that the hybrids did not produce any motor impairment effects. The results indicate that pyridazin-3(2H)-one derivatives may have potential therapeutic value for the management of mental depression.

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Abbreviations

1H NMR:

1H nuclear magnetic resonance

CDCl3 :

Deuterated chloroform

CHCl3 :

Chloroform

CNS:

Central nervous system

DMF:

Dimethylformamide

DMSOd6 :

Deuterated dimethylsulfoxide

ESI:

Electrospray ionization

FST:

Forced swimming test

HCl:

Chlohydric acid

IR:

Infrared

KBr:

Potassium bromide

LD:

Lethal dose

MAOIs:

Monoamine oxidase inhibitors

MDD:

Major depression disorder

NaOH:

Potassium hydroxide

SNRIs:

Serotonin–norepinephrine reuptake inhibitors

SSRIs:

Selective serotonin reuptake inhibitors

TCAs:

Tricyclic antidepressants

TMS:

Tetramethylsilane

TRI:

Triple reuptake inhibitors

USFDA:

United States Food and Drug Administration

WHO:

World Health Organization

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Acknowledgments

The authors are grateful to the University Mohammed V and Laboratory of control of drugs, Rabat-Morocco, for, IR, RMN and MASS spectra and the studies of antidepressant activity.

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Authors and Affiliations

  1. Laboratory of Therapeutic Chemistry, Faculty of Medicine and Pharmacy, BP 6203, Rabat Institutes, Mohammed V University, Rabat, Morocco

    Youness Boukharsa, Jamal Taoufik & M’hammed Ansar

  2. Laboratory of Pharmacology and Toxicology, Pharmacokinetic Research Team, Faculty of Medicine and Pharmacy, Rabat Institutes, Mohammed V University, Rabat, Morocco

    Bouchra Meddah, Ramata Yvette Tiendrebeogo, Yahia Cherrah & My El Abbes Faouzi

  3. Faculty of Medicine and Pharmacy, Research Center for Clinical Epidemiology and Therapeutic Trials, Mohammed V University, Rabat Institutes, Rabat, Morocco

    Ali Benomar

  4. Biotechnology Laboratory, Faculty of Medicine and Pharmacy, Rabat Institutes, Mohammed V University, Rabat, Morocco

    Azeddine Ibrahimi

Authors
  1. Youness Boukharsa
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  2. Bouchra Meddah
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  3. Ramata Yvette Tiendrebeogo
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  4. Azeddine Ibrahimi
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  5. Jamal Taoufik
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  6. Yahia Cherrah
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  7. Ali Benomar
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  8. My El Abbes Faouzi
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  9. M’hammed Ansar
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Corresponding author

Correspondence to M’hammed Ansar.

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Boukharsa, Y., Meddah, B., Tiendrebeogo, R.Y. et al. Synthesis and antidepressant activity of 5-(benzo[b]furan-2-ylmethyl)-6-methylpyridazin-3(2H)-one derivatives. Med Chem Res 25, 494–500 (2016). https://doi.org/10.1007/s00044-015-1490-x

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  • DOI: https://doi.org/10.1007/s00044-015-1490-x

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