from 01.01.2019 to 01.01.2021
Yaroslavl, Yaroslavl, Russian Federation
from 01.01.2017 to 01.01.2021
Yaroslavl, Yaroslavl, Russian Federation
Yaroslavl, Yaroslavl, Russian Federation
Yaroslavl, Yaroslavl, Russian Federation
Yaroslavl, Yaroslavl, Russian Federation
Several new short N-acyldipeptides containing the N-terminal 4-(1-adamantyl)benzoyl moiety have been synthesized using the classical peptide synthesis method in a solution based on N,N-carbonyldiimidazole. 1H NMR spectroscopy monitored the stereochemical purity of the desired compounds. It has been found that in the presence of an asymmetric carbon atom, a mixture of two diastereomers of N-acyldipeptides is formed in a non-contiguous amino acid residue. It has been suggested that this is due to the formation of an optically inactive oxazole intermediate at an intermediate stage. The synthesized compounds are of interest as potential therapeutic agents with antiviral activity in combination with low toxicity.
N-acyl dipeptides, N,N-carbonyl diamidazole, 4 - (1 adamantyl) benzoic acid, antiviral activity, diastereomers
1. Wanka L., Iqbal K., Schreiner P.R. The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives. Chem. Rev. 2013. Vol. 113. P. 3516-3604. DOI:https://doi.org/10.1021/cr100264t
2. Drakopoulos A., Tzitzoglaki C., Ma C. et al. Affinity of Rimantadine Enantiomers against Influenza A/M2 Protein Revisited. ACS Med. Chem. Lett. 2017. Vol. 8. Iss. 2. P. 145-150. DOI:https://doi.org/10.1021/acsmedchemlett.6b00311
3. Drakopoulos A., Tzitzoglaki C., McGuire K. et al. Unraveling the Binding, Proton Blockage, and Inhibition of Influenza M2 WT and S31N by Rimantadine Variants. ACS Med. Chem. Lett. 2018. Vol. 9. Iss. 3. P. 198-203. DOI:https://doi.org/10.1021/acsmedchemlett.7b00458
4. Wang L.-Y., Bu F.-Z., Yu Y.-M. et al. A novel crystalline molecular salt of sulfamethoxazole and amantadine hybridizing antiviral-antibacterial dual drugs with optimal in vitro/vivo pharmaceutical properties. Eur. J. Pharm. Sci. 2021. In Press. DOI:https://doi.org/10.1016/j.ejps.2021.105883
5. Liu H., Tian Y., Lee K. et al. Identification of Potent Ebola Virus Entry Inhibitors with Suitable Properties for in Vivo Studies. J. Med. Chem. 2018. Vol. 61. Iss. 14. P. 6293-6307. DOI:https://doi.org/10.1021/acs.jmedchem.8b00704
6. Shiryaev V.A., Radchenko E.V., Palyulin V.A. et al. Molecular design, synthesis and biological evaluation of cage compound-based inhibitors of hepatitis C virus p7 ion channels. Eur. J. Med. Chem. 2018. Vol. 158. P. 214-235. DOI:https://doi.org/10.1016/j.ejmech.2018.08.009
7. Shiryaev V.A., Skomorohov M.Y., Leonova M.V. et al. Adamantane derivatives as potential inhibitors of p37 major envelope protein and poxvirus reproduction. Design, synthesis and antiviral activity. Eur. J. Med. Chem. 2021. Vol. 221. Article 113485. DOI:https://doi.org/10.1016/j.ejmech.2021.113485
8. Wagner C.E., Mohler M.L., Kang G.S. et al. Synthesis of 1-Boraadamantaneamine Derivatives with Selective Astrocyte vs C6 Glioma Antiproliferative Activity. A Novel Class of Anti-Hepatitis C Agents with Potential to Bind CD81. J. Med. Chem. 2003. Vol. 46. P. 2823-2833. DOI:https://doi.org/10.1021/jm020326d
9. Shibnev V.A., Garaev T.M., Deryabin P.G. et al. Synthesis and pro-viral activity of adamantyl peptides against hepatitis C virus. Khimiko-farmatsevticheskii zhurnal. 2015. Vol. 49. N 7. P. 20-24 (in Russian).
10. Kotha S., Cheekatla S.R., Mhatre D.S. Ring-Closing Metathesis Approach to Cage Propellanes Containing Oxepane and Tetrahydrofuran Hybrid System. Synthesis. 2017. Vol. 49. P. 5339-5350. DOI:https://doi.org/10.1055/s-0036-1591726
11. Krasnikov S.V., Obuchova T.A., Yasinskii O.A., Balakin K.V. Synthesis of amino acid derivatives of 4-(l-adamantyl)benzoic acid obtained by transition metal ion catalyzed oxidation of 4-(l-adamantyl)toluene. Tetrahedron Lett. 2004. Vol. 4. P. 711-714. DOI:https://doi.org/10.1016/j.tetlet.2003.11.057
12. Nikitchenko E.A., Fedorov V.N., Krasnikov S.V., Obukhova T.A. Investigation of pharmacological properties of adamantyl benzoylaminoic acid derivatives. Farmatsiya. 2007. N 8. P. 37-38 (in Russian).
13. Krasnikov S.V., Remizova I.V., Obukhova T.A., Danilova A.S. Synthesis of optically pure peptide-like derivatives of 4-(1-adamantyl)benzoic acid. Izv. vuzov. Khimiya i khimicheskaya tekhnologiya. 2004. Vol. 47. Iss. 6. P. 110-113 (in Russian).
