Document 0435
 DOCN  M9490435
 TI    Synthesis of a series of
       4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin-2(1H-
       )-ones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors.
 DT    9411
 AU    Tucker TJ; Lyle TA; Wiscount CM; Britcher SF; Young SD; Sanders WM;
       Lumma WC; Goldman ME; O'Brien JA; Ball RG; et al; Merck Research
       Laboratories, West Point, Pennsylvania 19486.
 SO    J Med Chem. 1994 Jul 22;37(15):2437-44. Unique Identifier : AIDSLINE
       MED/94334899
 AB    As part of an ongoing effort to prepare novel non-nucleoside inhibitors
       of human immunodeficiency virus type-1 (HIV-1) reverse transcriptase
       (RT), a series of
       4-(arylethynyl)-6-chloro-4-cyclopropyl-3,4-dihydroquinazolin 2(1H)-ones
       4aa-l has been prepared. Target compounds 4a-e were synthesized via
       addition of various 1-lithio-2-(aryl)alkyne nucleophiles to a
       1-protected-4-cyclopropylquinazolin-2(1H)-one (7), followed by
       deprotection. The 3-methyl compound 4aa was prepared in an analogous
       manner, with the 3-alkylation performed prior to deprotection.
       Alternatively, the target compounds 4f-l were prepared by addition of
       1-lithio-2-(trimethylsilyl)acetylene to 7, followed by deprotection and
       subsequent palladium-catalyzed coupling with various aryl halides. By
       incorporating an aryl group onto the end of the 4-acetylene
       functionality, the requirement for a metabolically labile 3-methyl group
       on the dihydroquinazolinone nucleus has been eliminated. A number of the
       target compounds were shown to be potent inhibitors of HIV-1 RT.
       Compound 4a, which had exhibited the most favorable overall biological
       profile, was resolved via a four-step procedure to provide the
       enantiomers 13a and 13b. Compound 13a having the (-)-4(S) configuration
       was shown to be the active enantiomer and was selected as a candidate
       for further investigation.
 DE    Cells, Cultured  Crystallography, X-Ray  Human  HIV-1/*ENZYMOLOGY
       Quinazolines/CHEMICAL SYNTHESIS/*PHARMACOLOGY  Reverse
       Transcriptase/*ANTAGONISTS & INHIB  JOURNAL ARTICLE

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