4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones useful as HIV

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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5142358, 5142521, 51425202, 514241, 5142225, 544284, 544286, 544 5, 544116, 544257, 544264, 544238, 544 8, 544180, C07D40106, C07D40306, A61K 31517

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active

061243027

ABSTRACT:
The present invention relates to 4,4-disubstituted-3,4-dihydro-2(1H)-quinazolinones of formula I: ##STR1## or steroisomeric forms, stereoisomeric mixtures, or pharmaceutically acceptable salt forms thereof, which are useful as inhibitors of HIV reverse transcriptase, and to pharmaceutical compositions and diagnostic kits comprising the same, and methods of using the same for treating viral infection or as an assay standard or reagent, wherein:
R.sup.1 is C.sub.1-3 alkyl substituted with 1-7 halogen;
R.sup.2 is optionally substituted C.sub.1-5 alkyl, optionally substituted C.sub.2-5 alkenyl, or optionally substituted C.sub.2-5 alkynyl;
R.sup.3, at each occurrence, is independently selected from C.sub.1-4 alkyl, OH, C.sub.1-4 alkoxy, F, Cl, Br, I, NR.sup.5 R.sup.5a, NO.sub.2, CN, C(O)R.sup.6, NHC(O)R.sup.7, and NHC(O)NR.sup.5 R.sup.5a ;
R.sup.5 and R.sup.5a are independently selected from H and C.sub.1-3 alkyl;
R.sup.6 is selected from H, OH, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, and NR.sup.5 R.sup.5a ;
R.sup.7 is selected from C.sub.1-3 alkyl and C.sub.1-3 alkoxy;
R.sup.8 is selected from H, C.sub.3-5 cycloalkyl, and C.sub.1-3 alkyl; and,
n is selected from 0, 1, 2, 3, and 4.

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Tucker et al., J. Med. Chem, 1994, 37, 2437-2444, "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".
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