Design and Synthesis of P1-P3 Macrocyclic Tertiary-Alcohol-Comprising HIV-1 Protease Inhibitors
2013 (English)In: Journal of Medicinal Chemistry, ISSN 0022-2623, E-ISSN 1520-4804, Vol. 56, no 22, 8999-9007 p.Article in journal (Refereed) Published
To study P1-P3 macrocyclizations of previously reported tertiary-alcohol-comprising HIV-1 protease inhibitors (PIs), three new 14- and 15-member macrocyclic PIs were designed, synthesized by ring-closing metathesis, and evaluated alongside with 10 novel linear PIs. Cocrystallized complexes of the macrocyclic PIs and the HIV-1 protease are presented, analyzed, and discussed. The macrocyclic structures exhibited higher activities than the linear precursors with K-i and EC50 values down to 3.1 nM and 0.37 mu M, respectively.
Place, publisher, year, edition, pages
2013. Vol. 56, no 22, 8999-9007 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-214038DOI: 10.1021/jm400811dISI: 000327812600004OAI: oai:DiVA.org:uu-214038DiVA: diva2:684180