Synthesis of N-heterocyclic amides based on (+)-camphoric acid and study of their antiviral activity and pharmacokinetics

O I Yarovaya; D V Baranova; A S Sokolova; A G Nemolochnova; O P Sal'nikova; A V Fat'anova; A D Rogachev; A S Volobueva; V V Zarubaev; A G Pokrovsky; N F Salakhutdinov

doi:10.1007/s11172-023-3845-9

Synthesis of N-heterocyclic amides based on (+)-camphoric acid and study of their antiviral activity and pharmacokinetics

Russ Chem Bull. 2023;72(3):807-818. doi: 10.1007/s11172-023-3845-9. Epub 2023 Apr 15.

Authors

O I Yarovaya^{1

2}, D V Baranova¹, A S Sokolova¹, A G Nemolochnova^{1

2}, O P Sal'nikova², A V Fat'anova², A D Rogachev^{1

2}, A S Volobueva³, V V Zarubaev³, A G Pokrovsky², N F Salakhutdinov¹

Affiliations

¹ N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch of the Russian Academy of Sciences, 9 prosp. Akademika Lavrent'eva, 630090 Novosibirsk, Russian Federation.
² Novosibirsk State University, 2 ul. Pirogova, 630090 Novosibirsk, Russian Federation.
³ Pasteur Institute of Epidemiology and Microbiology, 14 ul. Mira, 197101 St. Petersburg, Russian Federation.

Abstract

Efficient conditions for the synthesis of nitrogen-containing heterocyclic derivatives of (1R,3S)(+)-camphoric acid were selected. A series of heterocyclic compounds based on (+)-camphoric acid bearing pharmacophoric fragments was synthesized using the developed methodology. The compounds were tested for their antiviral activity against SARS-CoV-2 and H1N1 influenza viruses, and efficient inhibitors were identified that are of significant interest for further studies. The stability of the compounds and pharmaco-kinetics of the leader compound were studied when administered intragastrically and intramuscularly to mice at a dose of 200 mg kg^-1 using the HPLC-MS/MS method.

Keywords: (+)-camphoric acid; A H1N1 influenza virus; N-heterocycles; SARS-CoV-2 virus; pharmacokinetics.