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Synthesis, characterization, and screening for analgesic and anti-inflammatory activities of new 1,3,4-oxadiazole derivatives linked to quinazolin-4-one ring

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Abstract

In the present study, several new 1,3,4-oxadiazole derivatives linked with quinazolin-4-one moiety were synthesized by following steps. 2-methyl -4H-3, 1-benzoxazin-4-one, and 2-phenyl -4H-3, 1-benzoxazin-4-one were synthesized in the first and second step by stirring anthranilic acid in pyridine with benzoyl chloride and with an acetic anhydride for 30 min at room temperature. On treatment with semicarbazide with the above synthesized intermediates, that is, 2-methyl-4H-3,1-benzoxazin-4-one, and 2-phenyl-4H-3,1-benzoxazin-4-one in the third step afforded 2-methyl-4-oxoquinazoline-3(4H)-carbohydrazide and 2-phenyl-4-oxoquinazoline-3(4H)-carbohydrazide. These were introduced in cyclization reaction with different aromatic acids, aromatic aldehydes, and carbon disulfide in the next step, producing the corresponding 3-(4-acetyl-5-aryl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2-phenyl-quinazolin-4(3H)-one derivatives, 3-(4-acetyl-5-aryl-4,5-dihydro-1,3,4-oxadiazol-2-yl)-2-methyl-quinazolin-4(3H)-one derivatives, 3-(5-aryl-1,3,4-oxadiazol-2-yl)-2-phenylquinazolin-4(3H)-one derivatives and 3-(5-aryl-1,3,4-oxadiazol-2-yl)-2-methylquinazolin-4(3H)-one derivatives. Purity of these synthesized derivatives was confirmed by thin layer chromatography, melting point. Structure of the derivatives was set up by determining infrared spectroscopy, nuclear magnetic resonance, and mass spectroscopy. All the synthesized derivatives were evaluated for their analgesic and anti-inflammatory activities in mice and rats. In animal studies, the derivatives 3-[4-acetyl-5-(2-hydroxyphenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-2-phenylquinazolin-4(3H)-one and 3-[4-acetyl-5-(4-hydroxy-3-methoxyphenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-2-phenylquinazolin-4(3H)-one shown more potent analgesic activity and the derivatives 3-[4-acetyl-5-(4-methoxyphenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-2-phenylquinazolin-4(3H)-one and 3-[4-acetyl-5-(4-methoxyphenyl)-4,5-dihydro-1,3,4-oxadiazol-2-yl]-2-methylquinazolin-4(3H)-one shown more potent anti-inflammatory activity as compared to other derivatives. The results of current study indicate that cyclization of carbohydrazide group of intermediate 2-methyl-4-oxoquinazoline-3(4H)-carbohydrazide and 2-phenyl-4-oxoquinazoline-3(4H)-carbohydrazide with different aromatic acids, aromatic aldehydes, and carbon disulfide produces novel quinazolin-4-one linked oxadiazole derivatives with potent analgesic and anti-inflammatory activities.

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Abbreviations

Ar:

Aromatic

COX:

Cyclo-oxygenase

FTIR:

Fourier transforms infrared spectroscopy

IAEC:

Institutional Animal Ethics Committee

IR:

Infrared spectroscopy

NSAIDs:

Non-steroidal anti-inflammatory drugs

NMR:

Nuclear magnetic resonance spectroscopy

OECD:

Organisation for Economic Co-operation and Development

Ppm:

Parts per million

SEM:

Standard error mean

Str:

Stretching

TLC:

Thin layer chromatography

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Acknowledgements

The authors thank to the Management of Rungta College of Pharmaceutical Sciences and Research, Bhilai, for providing necessary infrastructural facilities and IISER, Bhopal for providing immense help in the spectral analysis. The authors gratefully acknowledge the financial support received under Young Scientist Research Scheme (File No. SB/YS/LS-106/2014) of Science and Engineering Research Board (SERB), Department of Science and Technology, New Delhi, India.

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Authors and Affiliations

  1. Rungta College of Pharmaceutical Sciences and Research, Bhilai, 490024, Chhattisgarh, India

    Dhansay Dewangan, Vinay Sagar Verma, Kartik T. Nakhate & Dulal Krishna Tripathi

  2. Shri Rawatpura Sarkar Institute of Pharmaceutical Sciences, Kumhari, Chhattisgarh, India

    Pranita Kashyap & Hemant Dhongade

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  1. Dhansay Dewangan
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  2. Vinay Sagar Verma
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  3. Kartik T. Nakhate
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  4. Dulal Krishna Tripathi
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  5. Pranita Kashyap
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  6. Hemant Dhongade
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Correspondence to Dhansay Dewangan.

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Dewangan, D., Verma, V.S., Nakhate, K.T. et al. Synthesis, characterization, and screening for analgesic and anti-inflammatory activities of new 1,3,4-oxadiazole derivatives linked to quinazolin-4-one ring. Med Chem Res 25, 2143–2154 (2016). https://doi.org/10.1007/s00044-016-1641-8

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