       Document 0546
 DOCN  M9640546
 TI    Facile syntheses of C2-symmetrical HIV-1 protease inhibitors.
 DT    9604
 AU    Konig S; Ugi I; Schramm HJ; Max-Planck-Institute of Biochemistry,
       Martinsried, Germany.
 SO    Arch Pharm (Weinheim). 1995 Oct;328(10):699-704. Unique Identifier :
       AIDSLINE MED/96095533
 AB    With the goal of obtaining inexpensive yet potent anti-AIDS drugs,
       simple inhibitors of HIV-1 protease were synthesised. The C2-symmetrical
       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
       alpha,alpha'-dibromoketones 4a-d, we synthesised the diamino compounds
       6a-c by Gabriel synthesis, which were then coupled with Z-valine to
       yield inhibitors including a central hydroxy group 8a-d a-i by
       azidation, reduction with LiAlH4 and coupling of the
       beta,beta'-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 microM.
 DE    Alcohols/*CHEMICAL SYNTHESIS/PHARMACOLOGY  HIV Protease
       Inhibitors/*CHEMICAL SYNTHESIS/PHARMACOLOGY  HIV-1/*ENZYMOLOGY
       Ketones/*CHEMICAL SYNTHESIS/PHARMACOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

