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An assembly of structurally diverse small and simple 5-aminomethylene derivatives of 2,4-thiazolidinedione and studies of their biological activity

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Abstract

The synthesis of a novel series of substituted 5-(aminomethylene)thiazolidine-2,4-diones was achieved using a wide range of heterocyclic models derived from eight drug-like molecules. The primary aim of this study was to combine medicinally known, biologically active molecules bearing a 2° amine functionality, such as terbinafine, fluoxetine, atomoxetine, cetirizine, risperidone, aripiprazole, ziprasidone, and clopidogrel, with a thiazolidinedione ring via an amino-methylene linker. By targeting this synergistic approach to compounds with skeletal, functional, and stereochemical diversity, we have developed a simple synthetic concept to enrich the thiazolidinedione collection with various biological activities. The biological activities of the newly synthesized 5-(aminomethylene)thiazolidine-2,4-dione derivatives were explored. All compounds were found to have antibacterial activity, with compounds bearing pyridine or piperazine moieties showing good to excellent antibacterial activity. Compounds with piperazine moieties were also found to show good antifungal activity, whereas none of the synthesized compounds showed high cytotoxic activity.

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Notes

  1. Dr. Reddy’s Laboratories Ltd synthesized molecules from the basic commercial raw materials.

  2. Column purification with alumina using 2:98 methanol–dichloromethane.

  3. Compound was dissolved in 20 mL of methanol and ethyl acetate (10:90) in a glass vial. The clear solution was filtered through a syringe equipped with sintered glass fibers. For the growth of crystals, the clear solution was sealed and a controlled vapor leak allowed for slow solvent evaporation at a constant temperature (25 °C). Growth of the compound was continued for 4–5 days. Cambridge Crystallographic Data Centre: Deposition number: CCDC 1024959; Unit cell parameters: a = 26.8266(8) Å, b = 8.4308(2) Å, c = 20.5568(5) Å, P21/c.

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Acknowledgments

The authors thank the management of Dr. Reddy’s Laboratories Limited for giving support to carry out this work and also thank the analytical and process development team for their cooperation.

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Authors and Affiliations

  1. Process Research and Development, Dr. Reddy’s Laboratories Limited, API Plant, Bollaram-III, Plot No’s 116, 126C, Survey No. 157, S.V. Co-operative Industrial Estate, IDA Bollaram, Jinnaram Mandal, Medak District, Hyderabad, Andhra Pradesh, 502325, India

    Sandeep Mohanty & Sandeep G. Reddy

  2. Centre for Environment, Institute of Science and Technology, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad, Andhra Pradesh, 500072, India

    B. RamaDevi

  3. Shasun Pharmaceuticals Limited, Shasun Road, Periya Kalapet, Pondicherry, 605014, India

    Arun Chandra Karmakar

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  1. Sandeep Mohanty
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  2. Sandeep G. Reddy
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  3. B. RamaDevi
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  4. Arun Chandra Karmakar
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Correspondence to Sandeep Mohanty.

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Dr. Reddy’s Laboratories Limited communication number: IPDO IPM-00415.

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Mohanty, S., Reddy, S.G., RamaDevi, B. et al. An assembly of structurally diverse small and simple 5-aminomethylene derivatives of 2,4-thiazolidinedione and studies of their biological activity. Med Chem Res 24, 4037–4049 (2015). https://doi.org/10.1007/s00044-015-1447-0

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