Facile Syntheses of C2-Symmetrical HIV-1 Protease Inhibitors

✍ Scribed by Stephan König; Ivar Ugi; Hans J. Schramm

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 583 KB
• Volume: 328
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.19953281003

✦ Synopsis

With the goal of obtaining inexpensive yet potent anti-AIDS drugs, simple inhibitors of HIV-1 protease were synthesised. The C2symmetrical pseudopeptidic substrate analogues can be prepared as inhibitors for HIV-1 protease starting from symmetrical ketones 3a-d by a facile four-step synthesis. After bromination of 3a-d to a,a'-dibromoketones 4 a 4 , we synthesised the diamino compounds 6a-c by Gabriel synthesis, which were then coupled with Z-valine to yield inhibitors with a central keto group 2a-c. We also synthesised inhibitors including a central hydroxy group 8a-d a-i by azidation, reduction with LiAlH4 and coupling of the p,p'diaminohydroxy compounds with appropriate peptides. The first set of compounds showed only weak inhibition whereas the latter reach Ki values of up to 3.0 pM.