HIV INTEGRASE INHIBITORS

Yıl 2023, Cilt: 3 Sayı: 1, 23 - 30, 04.01.2023

Ferhat Güneş

Öz

HIV infection is incredibly detrimental and fatal to people. Unfortunately, despite recent advancements and medications, it has not yet been completely eradicated. Opportunistic infections are added to the list of disorders in AIDS (Acquired Immune Deficiency Syndrome), an infectious disease that develops as a result of an impaired immune system. In 2021, there were 38.4 million [33.9-43.8 million] persons living with HIV worldwide, up from 26.0 million [22.9-29.7 million] in 2000. The benefits of vastly expanded access to antiretrovirals, which have contributed to decreasing the number of individuals dying from HIV-related causes, can be observed in the persistence of HIV transmission despite declines in incidence. HIV-1 integration (IN), a critical stage in the integration of viral DNA into the host genome, is vital for retroviral replication. Numerous HIV integrase inhibitors have been created since the identification of this pathway, including Raltegravir, Elvitegravir, Dolutegravir, Bictegravir, and Cabotegravir. HIV integrase inhibitors and their synthesis are covered in this review.

Anahtar Kelimeler

Hiv, Integrase inhibitors, AIDS

Kaynakça

• 1. Piot P, Bartos M, Ghys PD, Walker N, Schwartländer B. The global impact of HIV/AIDS. Nature. 2001 Apr 19; 410: 968-73.
• 2. https://www.who.int/data/gho/data/indicators/indicator-details/GHO/estimated-number-of-people--living-with-hiv.Accessed 25 December 2022.
• 3. De Clercq E. Anti-HIV Drugs: 25 compounds approved within 25 years after the discovery of HIV. Int J Antimicrob Agents. 2009 Apr; 33: 307-20.
• 4. Ciuffi Angela, MechanismsGoverningLentivirus Integration Site Selection,Curr Gene Ther 2008; 8: 419-29.
• 5. Hajimahdi, Z., Zabihollahi, R., Aghasadeghi, M.R. et al. Novel quinolone-3-carboxylic acid derivatives as anti-HIV-1 agents: design, synthesis, and biological activities. MedChemRes. 2016; 25: 1861–1876.
• 6. Gill, M. S. A., Hassan, S. S., &Ahemad, N. Evolution of HIV-1 reverse transcriptase and integrase dual inhibitors: Recent advances and developments. Eur J MedChem. 2019; 179: 423-448.
• 7. J. Cocohoba, B.J. Dong, Raltegravir: the first HIV integrase inhibitor, Clin. Ther. 2008; 30: 1747–1765.
• 8. M. Sato, T. Motomura, H. Aramaki, T. Matsuda, M. Yamashita, Y. Ito, et al., Novel HIV-1 integrase inhibitors derived from quinolone antibiotics, J. Med. Chem. 2006; 49: 1506–1508.
• 9. Database. NCfBIP. Dolutegravir, CID=54726191.
• 10. M. Tsiang, G.S. Jones, J. Goldsmith, A. Mulato, D. Hansen, E. Kan, et al., Antiviral Activity of Bictegravir (GS-9883), a Novel Potent HIV-1 Integrase Strand Transfer Inhibitor with an Improved Resistance Profile, Antimicrob. AgentsChemother. 2016; 60: 7086–7097.
• 11. Karumanchi, K., Nangi, G. B. S., Danda, S. R., Chavakula, R., Korupolu, R. B., & Bonige, K. B. A Facile Synthesis of Raltegravir Potassium—An HIV Integrase Inhibitor. J HeterocyclChem. 2019; 56: 2683-2690.
• 12. (a) Wang, H.; Kowalski, M. D.; Lakdawala, A. S.; Vogt, F. G.; Wu, L. An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor. Org. Lett. 2015; 17: 564−567. (b) The route outlined in Schemes 2 and 3 was first disclosed in a 2011 patent application from ViiV Healthcare: Wang, H.; Goodman, S. N.; Mans, D.; Kowalski, M., Process for Preparing Carbamoylpyridone Derivatives and Intermediates, Int. Patent Appl. WO2011/119566 A1, Sep 29, 2011.
• 13. CHIU, Anna, et al. Synthesis of polycyclic-carbamoyl pyridine compounds. U.S. Patent No 10,975,096, 2021. 14. Hughes, D. L.Review of syntheticroutes and final forms of integrase inhibitors dolutegravir, cabotegravir, and bictegravir. Org Process Res Dev. 2019; 23: 716-729.