1075209-49-2Relevant articles and documents
A Photochemical Route to Optically Active Hexahydro-4 H-furopyranol, a High-Affinity P2 Ligand for HIV-1 Protease Inhibitors
Ghosh, Arun K.,Robinson, William L.
, p. 9801 - 9805 (2019/08/27)
We describe here the syntheses of optically pure (3aS,4S,7aR)-hexahydro-4H-furo[2,3-b]pyran-4-ol and (3aR,4R,7aS)-hexahydro-4H-furo[2,3-b]pyran-4-ol. These stereochemically defined heterocycles are important high-affinity P2 ligands for a variety of highl
Design and synthesis of potent HIV-1 protease inhibitors incorporating hexahydrofuropyranol-derived high affinity P2 ligands: Structure-activity studies and biological evaluation
Ghosh, Arun K.,Chapsal, Bruno D.,Baldridge, Abigail,Steffey, Melinda P.,Walters, D. Eric,Koh, Yasuhiro,Amano, Masayuki,Mitsuya, Hiroaki
, p. 622 - 634 (2011/03/21)
The design, synthesis, and evaluation of a new series of hexahydrofuropyranol-derived HIV-1 protease inhibitors are described. We have designed a stereochemically defined hexahydrofuropyranol-derived urethane as the P2-ligand. The current ligand is designed based upon the X-ray structure of 1a-bound HIV-1 protease. The synthesis of (3aS,4S,7aR)-hexahydro-2H-furo[2,3-b] pyran-4-ol, (-)-7, was carried out in optically active form. Incorporation of this ligand provided inhibitor 35a, which has shown excellent enzyme inhibitory activity and antiviral potency. Our structure-activity studies have indicated that the stereochemistry and the position of oxygens in the ligand are important to the observed potency of the inhibitor. Inhibitor 35a has maintained excellent potency against multidrug-resistant HIV-1 variants. An active site model of 35a was created based upon the X-ray structure of 1b-bound HIV-1 protease. The model offers molecular insights regarding ligand-binding site interactions of the hexahydrofuropyranol-derived novel P2-ligand.
