Development of Synthetic Approaches Towards HIV Integrase Strand Transfer Inhibitors (INSTIs)

• Published in: ChemistrySelect (Weinheim) Vol. 7; no. 29
• Main Authors: Sawant, Ashwini Amol, Jadav, Surender Singh, Nayani, Kiranmai, Mainkar, Prathama S.
• Format: Journal Article
• Language: English
• Published: 05.08.2022
• Subjects: HIV; inhibitors; INSTIs; integrase; synthesis
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202201915

A clear and precise report on synthetic methods for INSTIs and their intermediates are provided in the present work. HIV Integrase strand transfer inhibitors (INSTIs), a class of antiretroviral agents employed to treat HIV infected patients are placed as the second option of treatment after nucleosides. As INSTIs are employed as first line therapy to newly infected HIV positive individuals, thus synthetic routes must be easily accessible to the medicinal chemists towards lead optimization or process development. The current perspective elaborates synthetic routes of first to next generation INSTIs investigated in two decades of research and their development efforts. Further, drug resistance occurred by mutations against usage of INSTI drugs with respect to their generation also discussed. Later, discussion about synthetic development and investigation of next generation INSTIs against drug resistance HIV infections also covers to fill the gap between first/second generation INSTIs. The current perspective will draw attention of medicinal chemists and multi‐disciplinary researchers in HIV drug discovery. The current article covers synthetic strategies involved in the development of existing anti‐HIV drugs as well as small molecule INSTIs.