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Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives

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Abstract

A series of ten new compounds (7a–j) has been synthesized by absolutely replacing the glutamic acid part of Pemetrexed drug, chemically known as N-{4-[2-(2-amino-4-oxo-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoyl}-l-glutamic acid, with primary, secondary, and aryl amines in high yields using diethylphosphorocyanidate (DEPC) as a peptide coupling agent. All the synthesized compounds are characterized by 1H and 13C NMR, LCMS, and FT-IR spectral techniques. All the synthesized novel non-glutamate 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives showed 4- to 7-folds higher antiviral activity than its structurally similar commercial drug Pemetrexed against Newcastle disease virus, an avian paramyxovirus. Among the lot, compounds possessing carboxamide synthesized using five-membered heteroaryl amines (7i and 7j) exhibited the highest antiviral activity.

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Acknowledgements

We are thankful to the Management, Anthem Biosciences, Bangalore, India, for their invaluable support and allocation of resources for this work. We would like to thank the Analytical Chemistry team of Anthem Biosciences for carrying out all the analytical work.

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Authors and Affiliations

  1. Anthem Biosciences Pvt. Ltd., Bangalore, 560 099, India

    Selvakumar Balaraman

  2. National Institute of Animal Biotechnology, Hyderabad, 500 019, India

    Nagaraj Nayak & Madhuri Subbiah

  3. Department of Chemistry, Gandhigram Rural Institute (Deemed to be University), Gandhigram, 624 302, India

    Kuppanagounder P. Elango

Authors
  1. Selvakumar Balaraman
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  2. Nagaraj Nayak
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  3. Madhuri Subbiah
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  4. Kuppanagounder P. Elango
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Correspondence to Kuppanagounder P. Elango.

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Balaraman, S., Nayak, N., Subbiah, M. et al. Synthesis and antiviral study of novel 4-(2-(6-amino-4-oxo-4,5-dihydro-1H-pyrrolo[2,3-d]pyrimidin-3-yl)ethyl)benzamide derivatives. Med Chem Res 27, 2538–2546 (2018). https://doi.org/10.1007/s00044-018-2256-z

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  • DOI: https://doi.org/10.1007/s00044-018-2256-z

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