Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012:2012:237965.
doi: 10.1155/2012/237965. Epub 2012 Nov 28.

Synthesis and anticonvulsant activity of various mannich and schiff bases of 1,5-benzodiazepines

Surendra N Pandeya  1 , Neha Rajput  1
Affiliations

Synthesis and anticonvulsant activity of various mannich and schiff bases of 1,5-benzodiazepines

Surendra N Pandeya et al. Int J Med Chem. 2012.

Abstract

Benzodiazepines have a various behavioral effects in addition to their anxiolytic action. There is every reason to believe that the BZ/GABA receptor complex is involved in these effects, since GABAmimetic manipulations modify the effect of BZ in tests of convulsive activity, motor function, and appetitive behavior. 1,5-Benzodiazepines are biologically important molecules and are extensively used clinically as analgesic, hypnotic, sedative, and antidepressive agents. Hence, 1,5-Benzodiazepines were synthesized by condensation of o-phenylenediamine and ketones, for example, cyclohexanone and acetone in presence of sulfated zirconia (catalyst). Mannich bases were synthesized with acetophenone, p-nitroacetophenone, p-chloroacetophenone, and formaldehyde. Schiff bases were synthesized using Mannich base of 1,5-benzodiazepines with p-chloroaniline and p-chlorophenylsemicarbazide in the presence of glacial acetic acid. All the synthesized compounds were characterized by (1)H NMR and IR spectral analyses. All the synthesized derivatives were evaluated at the dose of 30 mg/kg b.w for anticonvulsant activity by isoniazid induced convulsion model, and the compounds NBZD-3 and NBZD-8 were found to be the most active among all compounds. Among all the synthesized derivatives, compounds NBZD-13 and NBZD-17 were found to be the most active among all compounds using thiosemicarbazide induced model. Although NBZD-8, NBZD-10, and NBZD-18 are the compounds which had shown good anticonvulsant activity and have an advantage over that, they were not sedative.

PubMed Disclaimer

Figures

Scheme 1
Scheme 1
Synthesis of fused ring benzodiazepine.
Scheme 2
Scheme 2
Synthesis of various Mannich base derivatives of fused ring benzodiazepines.
Scheme 3
Scheme 3
Synthesis of Schiff base derivative of fused ring benzodiazepine from p-chloroaniline.
Scheme 4
Scheme 4
Synthesis of Schiff base derivative of fused ring benzodiazepine from p-chlorophenylsemicarbazide.
Scheme 5
Scheme 5
Synthesis of 1,5-benzodiazepine (NBZD-12).
Scheme 6
Scheme 6
Synthesis of various Mannich base derivatives of 1,5-benzodiazepines.
Scheme 7
Scheme 7
Synthesis of Schiff base derivative of 1,5-benzodiazepine from p-chloroaniline.
Scheme 8
Scheme 8
Synthesis of Schiff base derivative of 1,5-benzodiazepine from p-chlorophenylsemicarbazide.
Scheme 9
Scheme 9
See this image and copyright information in PMC

References

    1. Page C, Michael C, Sutter M, Walker M, Hoffman B. Integrated Pharmacology. 2nd edition. Mosby; 2005.
    1. Archer GA, Sternbach LH. The chemistry of benzodiazepines. Chemical Reviews. 1968;68(6):747–784.
    1. Smith Jr. RH, Jorgensen WL, Tirado-Rives J, et al. Prediction of binding affinities for TIBO inhibitors of HIV-1 reverse transcriptase using Monte Carlo simulations in a linear response method. Journal of Medicinal Chemistry. 1998;41(26):5272–5286. - PubMed
    1. Rogowaski MA, Porter RJ. Antiepileptic drugs: pharmacological mechanisms and clinical efficacy with consideration of promising developmental stage compounds. Pharmacological Reviews. 1990;42(3):223–286. - PubMed
    1. Fisher R, Blum D. Clobazam, oxcarbazepine, tiagabine, topiramate, and other new antiepileptic drugs. Epilepsia. 1995;36(2):S105–S114. - PubMed

LinkOut - more resources