1007885-57-5Relevant academic research and scientific papers
Structural Analysis of Potent Hybrid HIV-1 Protease Inhibitors Containing Bis-tetrahydrofuran in a Pseudosymmetric Dipeptide Isostere
Rusere, Linah N.,Lockbaum, Gordon J.,Henes, Mina,Lee, Sook-Kyung,Spielvogel, Ean,Rao, Desaboini Nageswara,Kosovrasti, Klajdi,Nalivaika, Ellen A.,Swanstrom, Ronald,Kurt Yilmaz, Nese,Schiffer, Celia A.,Ali, Akbar
, p. 8296 - 8313 (2020)
The design, synthesis, and X-ray structural analysis of hybrid HIV-1 protease inhibitors (PIs) containing bis-tetrahydrofuran (bis-THF) in a pseudo-C2-symmetric dipeptide isostere are described. A series of PIs were synthesized by incorporating bis-THF of darunavir on either side of the Phe-Phe isostere of lopinavir in combination with hydrophobic amino acids on the opposite P2/P2′ position. Structure-activity relationship studies indicated that the bis-THF moiety can be attached at either the P2 or P2′ position without significantly affecting potency. However, the group on the opposite P2/P2′ position had a dramatic effect on potency depending on the size and shape of the side chain. Cocrystal structures of inhibitors with wild-type HIV-1 protease revealed that the bis-THF moiety retained similar interactions as observed in the darunavir-protease complex regardless of the position on the Phe-Phe isostere. Analyses of cocrystal structures and molecular dynamics simulations provide insights into optimizing HIV-1 PIs containing bis-THF in non-sulfonamide dipeptide isosteres.
Matched and mixed cap derivatives in the tetracyclic indole class of HCV NS5A inhibitors
Dwyer, Michael P.,Keertikar, Kerry M.,Chen, Lei,Tong, Ling,Selyutin, Oleg,Nair, Anilkumar G.,Yu, Wensheng,Zhou, Guowei,Lavey, Brian J.,Yang, De-Yi,Wong, Michael,Kim, Seong Heon,Coburn, Craig A.,Rosenblum, Stuart B.,Zeng, Qingbei,Jiang, Yueheng,Shankar, Bandarpalle B.,Rizvi, Razia,Nomeir, Amin A.,Liu, Rong,Agrawal, Sony,Xia, Ellen,Kong, Rong,Zhai, Ying,Ingravallo, Paul,Asante-Appiah, Ernest,Kozlowski, Joseph A.
, p. 4106 - 4111 (2016/08/01)
A matched and mixed capping SAR study was conducted on the tetracyclic indole class of HCV NS5A inhibitors to examine the influence of modifications of this region on the overall HCV virologic resistance profiles.
