Document 0079
 DOCN  M9590079
 TI    Design and synthesis of novel inhibitors of HIV-1 reverse transcriptase.
 DT    9509
 AU    Maruenda H; Johnson F; Chemistry Department, State University of New
       York at Stony Brook; 11794-3400, USA.
 SO    J Med Chem. 1995 Jun 9;38(12):2145-51. Unique Identifier : AIDSLINE
       MED/95302434
 AB    A variety of N1-substituted pyrimido[5,4-f]benzo[1,4]thiazepines, 5,
       designed as conformationally constrained analogs of
       1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymidine HEPT (1), were
       synthesized and evaluated for their inhibition of human immunodeficiency
       virus type 1 (HIV-1) reverse transcriptase (RT). The preparation of
       these compounds was carried out based on a Mannich-type cyclization of
       6-[(2-aminophenyl)thio]uracils followed by alkylation at N1 by a one-pot
       Vorbruggen reaction. The pyrimidobenzothiazepines were developed to give
       molecules with IC50 values in the micromolar range, as exemplified by
       [[(2-ethoxyethyl)oxy]methyl]-pyrimido[5,4- f]benzo[1,4]thiazepine, 25,
       (IC50 = 0.64 microM), the most active compound of this series. The
       structural and electronic features of this novel class of HIV-1 RT
       inhibitors are presented and compared with those of HEPT (1), TIBO (2),
       and nevirapine (3).
 DE    Crystallography, X-Ray  *Drug Design  HIV-1/*ENZYMOLOGY  Molecular
       Structure  Reverse Transcriptase/*ANTAGONISTS & INHIB  Support, U.S.
       Gov't, P.H.S.  Thiazepines/CHEMISTRY/*CHEMICAL SYNTHESIS/PHARMACOLOGY
       JOURNAL ARTICLE

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