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Design, Synthesis, and Pharmacological Activity of a New Matrix Metalloproteinase-9 Inhibitor

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Pharmaceutical Chemistry Journal Aims and scope

The new MMP-9 inhibitor 1-{4-[(4-chlorobenzoyl)amino]phenyl}sulfonyl-L-proline, with a theoretical inhibition constant of IC50 = 4 × 105 M, was constructed on the basis of structural requirements for selective inhibitors of gelatinases. This constructed compound and its close structural analogs were synthesized and these substances were found to have low toxicity, (LD50 > 300 mg/kg). The new inhibitor given p.o. at a dose of 20 mg/kg/day on the background of acute myocardial infarction significantly decreased the content of immunoreactive MMP-9 in plasma in rats, to the level obtained with doxycycline.

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Authors and Affiliations

  1. V. V. Zakusov Science Research Institute of Pharmacology, 8 Baltiiskaya Street, 125315, Moscow, Russia

    O. S. Grigorkevich, G. V. Mokrov, A. S. Dyabina, V. N. Stolyaruk, I. B. Tsorin, E. O. Ionova, S. A. Kryzhanovskii, T. A. Gudasheva & A. D. Durnev

Authors
  1. O. S. Grigorkevich
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  2. G. V. Mokrov
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  3. A. S. Dyabina
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  4. V. N. Stolyaruk
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  5. I. B. Tsorin
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  6. E. O. Ionova
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  7. S. A. Kryzhanovskii
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  8. T. A. Gudasheva
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  9. A. D. Durnev
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Corresponding author

Correspondence to T. A. Gudasheva.

Additional information

Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 52, No. 1, pp. 8 – 14, January, 2018.

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Grigorkevich, O.S., Mokrov, G.V., Dyabina, A.S. et al. Design, Synthesis, and Pharmacological Activity of a New Matrix Metalloproteinase-9 Inhibitor. Pharm Chem J 52, 30–36 (2018). https://doi.org/10.1007/s11094-018-1761-1

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  • DOI: https://doi.org/10.1007/s11094-018-1761-1

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