680219-95-8Relevant articles and documents
Flexible cyclic ethers/polyethers as novel P2-ligands for HIV-1 protease inhibitors: Design, synthesis, biological evaluation, and protein-ligand X-ray studies
Ghosh, Aran K.,Gemma, Sandra,Baldridge, Abigail,Wang, Yuan-Fang,Kovalevsky, Andrey Yu.,Koh, Yashiro,Weber, Irene T.,Mitsuya, Hiroaki
body text, p. 6021 - 6033 (2009/10/23)
We report the design, synthesis, and biological evaluation of a series of novel HIV-1 protease inhibitors. The inhibitors incorporate stereochemically defined flexible cyclic ethers/polyethers as high affinity P2-ligands. Inhibitors containing small ring 1,3-dioxacycloalkanes have shown potent enzyme inhibitory and antiviral activity. Inhibitors 3d and 3h are the most active inhibitors. Inhibitor 3d maintains excellent potency against a variety of multi-PI-resistant clinical strains. Our structure-activity studies indicate that the ring size, stereochemistry, and position of oxygens are important for the observed activity. Optically active synthesis of 1,3-dioxepan-5-ol along with the syntheses of various cyclic ether and polyether ligands have been described. A protein-ligand X-ray crystal structure of 3d-bound HIV-1 protease was determined. The structure revealed that the P2-ligand makes extensive interactions including hydrogen bonding with the protease backbone in the S2-site. In addition, the P2-ligand in 3d forms a unique water-mediated interaction with the NH of Gly-48.
Synthesis of novel cationic cardiolipin analogues for the optimal delivery of therapeutic agents
Kasireddy, Krishnudu,Ahmad, Moghis U.,Ali, Shoukath M.,Ahmad, Imran
, p. 2743 - 2746 (2007/10/03)
A novel approach was developed to synthesize cardiolipin analogues containing two quaternary ammonium groups with tetraalkyl chain retaining 'glycerol' moiety, the central core of the molecule. The analogues were synthesized with or without spacer and/or
