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Synthesis of a New Series of 4-Aryl-1,4-Dihydropyridines with Calcium Channel Blocking and Vasodilatory Activity

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Abstract

Several new amide derivatives of 4-aryl-1,4-dihydropyridine carboxylic congeners have been synthesized in this study to obtain therapeutically useful compounds. The changes in pharmacological properties of dihydropyridines by the presence of polar groups at different positions of 4-phenyl substituent and also by introduction of unsymmetrical ester groups in the synthesized symmetrical analogs have been studied. In vitro calcium channel blocking activity has been evaluated in cultures of neonatal rat cortical neurons by measuring the inhibitory response at L-type calcium channels activated by veratridine. The newly synthesized dihydropyridines displayed moderate calcium channel blockade with IC50 values ranging from 2 to 10 μM in comparison to nifedipine (IC50 = 57.7 nM). The vasodilatory activity was evaluated on isolated rat thoracic aortic rings precontracted by phenylephrine/KCl (30 mM). The symmetrically substituted dihydropyridine 8a exhibited maximum activity with IC50 = 0.64 μM but was found to be approximately 24 times less active in comparison to standard drug nifedipine with IC50 = 27.5 nM.

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Acknowledgments

The authors are thankful to University Grants Commission, India for providing financial support.

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Authors and Affiliations

  1. University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, 160014, India

    Ranju Bansal & Priyanka Jain

  2. Departamento de Fisiología y Farmacología, Facultad de Farmacia, Campus “Miguel de Unamuno”, 37007, Salamanca, Spain

    Carmen Calle & Rosalia Carron

  3. Thistle Technologies, 11 Sycamore Way, Branford, 06405, USA

    Karen Pemberton

  4. Strathclyde Institute for Drug Research and Department of Physiology and Pharmacology, University of Strathclyde, 27 Taylor Street, Glasgow, G4 0NR, UK

    Alan L. Harvey

Authors
  1. Ranju Bansal
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  2. Priyanka Jain
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  3. Carmen Calle
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  4. Rosalia Carron
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  5. Karen Pemberton
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  6. Alan L. Harvey
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Correspondence to Ranju Bansal.

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Bansal, R., Jain, P., Calle, C. et al. Synthesis of a New Series of 4-Aryl-1,4-Dihydropyridines with Calcium Channel Blocking and Vasodilatory Activity. Med Chem Res 21, 908–921 (2012). https://doi.org/10.1007/s00044-011-9600-x

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  • DOI: https://doi.org/10.1007/s00044-011-9600-x

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