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Synthesis and Anticoagulant Activity of New Functionalized 4H-Pyrrolo[3,2,1-ij]quinolin-2-ones

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Abstract

The reduction of 4,4,6-trimethyl-4H-pyrrolo[3,2,1-ij]quinoline-1,2-diones with aqueous hydrazine hydrate selectively involved the C1=O carbonyl group to give the corresponding 4,4,6-trimethyl-4H-pyrrolo­[3,2,1-ij]quinolin-2(1H)-ones within a few hours. The reduction products were condensed with aldehydes and acetone to afford new 1-[(het)arylmethylidene]- and 1-(propan-2-ylidene)-4H-pyrrolo[3,2,1-ij]quinolin-2(1H)-ones in 59–78% yield. The reaction of 4,4,6-trimethyl-4H-pyrrolo[3,2,1-ij]quinolin-2(1H)-ones with N,N-di­methylformamide dimethyl acetal, followed by transamination with primary amines led to the formation of 1-{[(het)arylamino]methylidene}-4H-pyrrolo[3,2,1-ij]quinolin-2-ones in 65–83% yield. The synthesized compounds were evaluated for their anticoagulant activity by measuring inhibition of blood coagulation factors Xa and XIa.

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Notes

  1. Values in brackets refer to the E isomer.

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ACKNOWLEDGMENTS

The high-resolution mass spectra were recorded at the joint research equipment center at the Voronezh State University.

Funding

This study was performed under financial support by the Russian Science Foundation (project no. 18-74-10097, https://rscf.ru/project/18-74-10097).

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Authors and Affiliations

  1. Voronezh State University, 394018, Voronezh, Russia

    N. P. Novichikhina, Z. E. Ashrafova, I. V. Ledenyova & Kh. S. Shikhaliev

  2. Federal Research and Clinical Center of Pediatric Hematology, Oncology, and Immunology, Ministry of Health of the Russian Federation, 117997, Moscow, Russia

    N. A. Podoplelova

  3. Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences, 109029, Moscow, Russia

    M. A. Panteleev

Authors
  1. N. P. Novichikhina
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  2. Z. E. Ashrafova
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  4. N. A. Podoplelova
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  5. M. A. Panteleev
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  6. Kh. S. Shikhaliev
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Correspondence to Kh. S. Shikhaliev.

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Translated from Zhurnal Organicheskoi Khimii, 2022, Vol. 58, No. 9, pp. 965–974 https://doi.org/10.31857/S0514749222090051.

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Novichikhina, N.P., Ashrafova, Z.E., Ledenyova, I.V. et al. Synthesis and Anticoagulant Activity of New Functionalized 4H-Pyrrolo[3,2,1-ij]quinolin-2-ones. Russ J Org Chem 58, 1225–1232 (2022). https://doi.org/10.1134/S1070428022090056

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