Claims for Patent: 6,878,717

Summary for Patent: 6,878,717

Title:	HIV replication inhibiting pyrimidines
Abstract:	This invention concerns the use of compounds of formula: ##STR1## the N-oxides, the pharmaceutically acceptable addition salts, quaternary amines and the stereochemically isomeric forms thereof, wherein -a.sup.1 =-a.sup.2 -a.sup.3 =a.sup.4 - forms a phenyl, pyridinyl, pyrimidinyl, pyridazinyl or pyrazinyl with the attached vinyl group; n is 0 to 4; and where possible 5; R.sup.1 is hydrogen, aryl, formyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxy-carbonyl, substituted C.sub.1-6 alkyl, or substituted C.sub.1-6 alkyloxyC.sub.1-6 alkylcarbonyl; each R.sup.2 independently is hydroxy, halo, optionally substituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl, C.sub.3-7 cycloalkyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalo-methylthio, --S(.dbd.O).sub.p R.sup.6, --NH--S(.dbd.O).sub.p R.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or a 5-membered heterocyclic ring; p is 1 or 2; L is optionally substituted C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.2-10 alkynyl or C.sub.3-7 cycloalkyl; or L is --X--R.sup.3 wherein R.sup.3 is optionally substituted phenyl, pyridinyl, pyrimidinyl, pyrazinyl or pyridazinyl; X is --NR.sup.1 --, --NH--NH--, --N.dbd.N--, --O--, --C(.dbd.O)--, --CHOH--, --S--, --S(.dbd.O)-- or --S(.dbd.O).sub.2 --; Q is hydrogen, C.sub.1-6 alkyl, halo, polyhalo-C.sub.1-6 alkyl or an optionally substituted amino group; Y represents hydroxy, halo, C.sub.3-7 cycloalkyl, optionally substituted C.sub.1-6 alkyl, C.sub.2-6 alkenyl or C.sub.2-6 alkynyl, C.sub.1-6 alkyloxy, C.sub.1-6 alkyloxycarbonyl, carboxyl, cyano, nitro, amino, mono- or di(C.sub.1-6 alkyl)amino, polyhalomethyl, polyhalomethyloxy, polyhalomethylthio, --S(.dbd.O).sub.p R.sup.6, --NH--S(.dbd.O).sub.p R.sup.6, --C(.dbd.O)R.sup.6, --NHC(.dbd.O)H, --C(.dbd.O)NHNH.sub.2, --NHC(.dbd.O)R.sup.6, --C(.dbd.NH)R.sup.6 or aryl; aryl is optionally substituted phenyl; Het is an optionally substituted heterocyclic radical; for the manufacture of a medicine for the treatment of subjects suffering from HIV (Human Immunodeficiency Virus) infection.
Inventor(s):	De Corte; Bart (Southampton, PA), De Jonge; Marc Rene (5045 CA Tilburg, NL), Heeres; Jan (Vosselaar, BE), Ho; Chih Yung (Lansdale, PA), Janssen; Paul Adriaan Jan (B2350 Vosselaar, BE), Kavash; Robert W. (Maple Glen, PA), Koymans; Lucien Maria Henricus (B-2300 Turnhout, BE), Kukla; Michael Joseph (Maple Glen, PA), Ludovici; Donald William (Quakertown, PA), Van Aken; Koen Jeanne Alfons (B-2300 Turnhout, BE)
Assignee:
Application Number:	09/430,966
Patent Claims:	1. A method of treating subjects suffering from HIV (Human Immunodeficiency Virus) infection comprising administering to the subject a therapeutically effective amount of a compound of formula: ##STR32## a N-oxide, a pharmaceutically acceptable addition salt, or a stereochemically isomeric form thereof, wherein -a.sup.1 =a.sup.2 -a.sup.3 =a.sup.4 - represents a bivalent radical of formula: 2. The method of claim 1, wherein R.sup.1 is hydrogen, aryl, formyl, C.sub.1-6 alkylcarbonyl, C.sub.1-6 alkyl, C.sub.1-6 alkyloxycarbonyl, C.sub.1-6 alkyl substituted with formyl, C.sub.1-6 alkylcarbonyl, or C.sub.1-6 alkyloxycarbonyl. 3. A method of treating non-nucleoside reverse transcriptase inhibitor resistant HIV infection in a subject in need thereof comprising administering to the subject an effective amount of a compound having the formula: ##STR34## a N-oxide, an addition salt, or a stereochemically isomeric form thereof, wherein -b.sup.1 =b.sup.2 -C(R.sup.2a)=b.sup.3 -b.sup.4 = represents a bivalent radical of formula: 4. A method of treating non-nucleoside reverse transcriptase inhibitor resistant HIV-1 infection in a subject in need thereof comprising administering to the subject an effective amount of a compound having the formula: ##STR36## a N-oxide, an addition salt, or a stereochemically isomeric form thereof, wherein -b.sup.1 =b.sup.2 -C(R.sup.2a)=b.sup.3 -b.sup.4 = represents a bivalent radical of formula: 5. A method of treating subjects suffering from HIV (Human Immunodeficiency Virus) infection comprising administering to the subject a therapeutically effective amount of a compound of formula: ##STR38## a N-oxide, an addition salt, a quaternary amine or a stereochemically isomeric form thereof, wherein -b.sup.1 =b.sup.2 -C(R.sup.2a)=b.sup.3 -b.sup.4 = represents a bivalent radical of formula: