883976-51-0Relevant articles and documents
COMPOUNDS AND METHODS FOR TREATING AIDS AND HIV INFECTIONS
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Page/Page column 36, (2010/12/17)
Macrocycle containing carbamate compounds that inhibit HIV proteolytic enzymes and processes for preparing them are described. Compositions and methods for treating a patient infected with HIV are described.
Design, synthesis, protein-ligand X-ray structure, and biological evaluation of a series of novel macrocyclic human immunodeficiency virus-1 protease inhibitors to combat drug resistance
Ghosh, Arun K.,Kulkarni, Sarang,Anderson, David D.,Hong, Lin,Baldridge, Abigail,Wang, Yuan-Fang,Chumanevich, Alexander A.,Kovalevsky, Andrey Y.,Tojo, Yasushi,Amano, Masayuki,Koh, Yasuhiro,Tang, Jordan,Weber, Irene T.,Mitsuya, Hiroaki
experimental part, p. 7689 - 7705 (2010/05/19)
The structure-based design, synthesis, and biological evaluation of a series of nonpeptidic macrocyclic HIV protease inhibitors are described. The inhibitors are designed to effectively fill in the hydrophobic pocket in the S1′ - S2′ subsites and retain all major hydrogen bonding interactions with the protein backbone similar to darunavir (1) or inhibitor 2. The ring size, the effect of methyl substitution, and unsaturation within the macrocyclic ring structure were assessed. In general, cyclic inhibitors were significantly more potent than their acyclic homologues, saturated rings were less active than their unsaturated analogues and a preference for 10- and 13-membered macrocylic rings was revealed. The addition of methyl substituents resulted in a reduction of potency. Both inhibitors 14b and 14c exhibited marked enzyme inhibitory and antiviral activity, and they exerted potent activity against multidrug-resistant HIV-1 variants. Protein - ligand X-ray structures of inhibitors 2 and 14c provided critical molecular insights into the ligand-binding site interactions.
Design and synthesis of novel HIV-1 protease inhibitors incorporating oxyindoles as the P′2-ligands
Ghosh, Arun K.,Schiltz, Gary,Perali, Ramu Sridhar,Leshchenko, Sofiya,Kay, Stephanie,Walters, D. Eric,Koh, Yasuhiro,Maeda, Kenji,Mitsuya, Hiroaki
, p. 1869 - 1873 (2007/10/03)
A series of novel oxyindole-derived HIV-1 protease inhibitors were designed and synthesized based upon our X-ray crystal structure of inhibitor 2 (TMC-114) bound to HIV-1 protease. The effects of substituents, spirocyclic rings, and ring sizes have been investigated. A number of inhibitors exhibited low nanomolar inhibitory potencies against HIV protease.
