138498-62-1Relevant articles and documents
Highly Diastereoselective Alkylations of Chiral Amide Enolates: New Routes to Hydroxyethylene Dipeptide Isostere Inhibitors of HIV-1 Protease
Askin, D.,Wallace, M. A.,Vacca, J. P.,Reamer, R. A.,Volante, R. P.,Shinkai, I.
, p. 2771 - 2773 (2007/10/02)
The nonchelate enforced chiral amide enolates derived from 4-7 react with alkyl iodide and protected α-amino epoxide electrophiles to produce the HIV protease inhibitors 10 and 16-19 with high diastereoselectivity.
Synthesis and antiviral activity of a series of HIV-1 protease inhibitors with functionality tethered to the P1 or P1'phenyl substituents: X-ray crystal structure assisted design
Thompson,Fitzgerald,Holloway,Emini,Darke,McKeever,Schleif,Quintero,Zugay,Tucker,Schwering,Homnick,Nunberg,Springer,Huff
, p. 1685 - 1701 (2007/10/02)
By tethering of a polar hydrophilic group to the P1 or P1' substituent of a Phe-based hydroxyethylene isostere, the antiviral potency of a series of HIV protease inhibitors was improved. The optimum enhancement of anti-HIV activity was observed with the 4-morpholinylethoxy substituent. The substituent effect is consistent with a model derived from inhibitor docked in the crystal structure of the native enzyme. An X-ray crystal structure of the inhibited enzyme determined to 2.25 A verifies the modeling predictions.