The synthesis of 2-amino-4-aryl-4H-pyrano[3,2-c][1,2] benzoxathiine-3-carbonitrile 5,5-dioxides and the study of their effect on the blood coagulation process

G. V. Grygoriv; D. A. Lega; L. M. Shemchuk; L. M. Maloshtan; G. S. Kalenichenko; V. P. Chernykh; L. A. Shemchuk

doi:10.24959/nphj.18.2224

Authors

G. V. Grygoriv National University of Pharmacy, Ukraine https://orcid.org/0000-0001-6761-4478
D. A. Lega National University of Pharmacy, Ukraine https://orcid.org/0000-0002-4505-3646
L. M. Shemchuk National University of Pharmacy, Ukraine
L. M. Maloshtan National University of Pharmacy, Ukraine
G. S. Kalenichenko National University of Pharmacy, Ukraine
V. P. Chernykh National University of Pharmacy, Ukraine
L. A. Shemchuk National University of Pharmacy, Ukraine

DOI:

https://doi.org/10.24959/nphj.18.2224

Keywords:

1, 2-benzoxathiin-4(3H)-one 2, 2-dioxide, aromatic aldehydes, malononitrile, 4H-pyran, anticoagulant activity, hemostatic activity

Abstract

To date, coumaric oral anticoagulants are the worldwide standard for thrombosis treatment. However, representatives of this group also possess a number of undesirable side effects; therefore, the search for novel anticoagulants are still in progress.

Aim. To synthesize 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides and study their effect on the blood coagulation process.

Results and discussion. Reflux of equimolar quantities of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide with malononitrile and arenecarbaldehydes for 1 h in ethanol with the catalytic amount of triethylamine led to formation of 2-amino4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides. A wide range of substituted aromatic aldehydes was used for further study of the “structure – biological activity” relationship. Among the compounds synthesized substances with anticoagulant and hemostatic properties were found.

Experimental part. A series of 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides was synthesized. The effect of the compounds obtained on the blood coagulation process was studied in vitro by the Burker method.

Conclusions. The target 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides can be easily obtained with moderate to high yields in the three-component interaction of 1,2-benzoxathiin-4(3H)-one 2,2-dioxide, malononitrile and arenecarbaldehydes. According to the in vitro studies both anticoagulant and hemostatic substances with relatively high levels of the activities were found among this novel heterocyclic group of compounds. Thus, the effect of 2-amino-4-aryl-4H-pyrano[3,2-c][1,2]benzoxathiine-3-carbonitrile 5,5-dioxides on the blood coagulation process requires further detailed study.

Author Biographies

G. V. Grygoriv, National University of Pharmacy

postgraduate student of the Organic Chemistry Department

D. A. Lega, National University of Pharmacy

Candidate of Pharmacy (Ph.D.), teaching assistant of the Organic Chemistry Department

L. M. Shemchuk, National University of Pharmacy

Candidate of Chemistry (Ph.D.), associate professor of the Organic Chemistry Department

L. M. Maloshtan, National University of Pharmacy

Doctor of Biology (Dr. habil.), professor, head of the Human Physiology and Anatomy Department

G. S. Kalenichenko, National University of Pharmacy

Candidate of Pharmacy (Ph.D.), teaching assistant of the Human Physiology and Anatomy Department

V. P. Chernykh, National University of Pharmacy

Doctor of Chemistry (Dr. habil.), Doctor of Pharmacy (Dr. habil.), professor of the Organic Chemistry Department, academician of the National Academy of Sciences of Ukraine

L. A. Shemchuk, National University of Pharmacy

Doctor of Chemistry (Dr. habil.), professor, head of the Organic Chemistry Department

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