Skip to main content
. 2024 Mar 27;25(7):3734. doi: 10.3390/ijms25073734

Figure 1.

Figure 1

Design of novel HIV CA-targeting chemotypes. (A) Chemical structures of 1, PF74, and 2, GS-6207. (B) Docking of the two best-known CA inhibitors 1, PF74 (cyan), and 2, GS-6207 (crimson), into the presumed binding pocket (PDB: 4XFZ). Overlay shows that both chemical scaffolds bind similarly. (C) Chemical profiling of 1, PF74, identified analog 3 as a potent stabilizer and analog 4 as a unique destabilizer. Molecular hybridization led to the design of hybrids 5 and 6. (D) Modular synthetic approach entailing the key skeleton C2 (8a,b) and sequential reactions with C1 (7, Suzuki), C4 (10, Sonogashira), and C3 (9a,b, amide coupling). Asterisks (*) indicate stereocenters with undefined configurations.