Document 0873
 DOCN  M9650873
 TI    An alternate synthesis of the Tat-antagonist
       7-chloro-N-methyl-5-(1H-pyrrol-2-yl)-3H-1,4-benzodiazepin-2-amine- .
 DT    9605
 AU    Maehr H; Zenchoff G; Coffen DL; Roche Research Center, Hoffmann La Roche
       Inc., Nutley, NJ 07110,; USA.
 SO    Bioorg Med Chem. 1995 Apr;3(4):391-5. Unique Identifier : AIDSLINE
       MED/96172304
 AB    An alternative synthesis of
       7-chloro-N-methyl-5-(1H-pyrrol-2-yl)-3H-1,4-benzodiazepin-2-amine- , the
       compound that inhibits gene expression by HIV-1 at the level of
       transcriptional transactivation by Tat, has been developed. The process
       is based on ring expansion of
       6-chloro-2-chloromethyl-4-(1H-pyrrol-2-yl)quinazoline 3-oxide which
       leads to the corresponding benzodiazepine Ro24-7429. Quinazoline 3-oxide
       formation in the presence of boron trifluoride gives a tetracyclic
       system containing a 2,2-difluoro-1,3,6,2-oxadiazaborine ring that
       survives ring expansion to
       13-chloro-5,5-difluoro-9-(methylamino)-5H-pyrrolo[1',2':3,4]-
       1,3,6,2-oxadiazabora[6,5-d]-8H-1,4-benzodiazepin-7-ium hydroxide inner
       salt. This unusual benzodiazepine does not significantly inhibit
       Tat-mediated gene expression by HIV-1.
 DE    Benzodiazepines/*CHEMICAL SYNTHESIS/PHARMACOLOGY  Gene Products,
       tat/*ANTAGONISTS & INHIB  Human  HIV-1/DRUG EFFECTS
       Methylamines/CHEMISTRY  Models, Molecular  Molecular Structure  Nuclear
       Magnetic Resonance  Virus Replication/DRUG EFFECTS  JOURNAL ARTICLE

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