N-aryl and N-heteroarylamide and urea derivatives as inhibitors of acyl coenzyme A: cholesterol acyl transferase (ACAT)

A compound of the formula ##STR9## wherein Q is --CR.sup.2 R.sup.3 R.sup.4 or --NR.sup.17 TR.sup.18 ;

• R.sup.1 is ##STR10## R.sup.2, R.sup.3 and R.sup.4 may be the same or different, and (a) are selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, A, XR.sup.10, phenyl-(C.sub.1 -C.sub.7) alkyl, and (C.sub.5 -C.sub.6) cycloalkyl-(C.sub.1 -C.sub.6) alkyl, with the proviso that at least one of R.sup.2, R.sup.3 and R.sup.4 must be A, and with the proviso that when R.sup.1 is is NR.sup.19 R.sup.20, (C.sub.1 -C.sub.6)alkylthio, (C.sub.5 -C.sub.7)cycloalkylthio, phenyl (C.sub.1 -C.sub.6)alkylthio, phenylthio or heteroalkylthio, either at least one of R.sup.2, R.sup.3 and R.sup.4 must be XR.sup.10, or two of R.sup.2, R.sup.3 and R.sup.4 must be A;
• or
• (b) R.sup.2 and R.sup.3 together with the carbon to which they are attached form a cyclic or bicyclic system selected from the group consisting of (C.sub.3 -C.sub.7) cycloalkyl, (C.sub.3 -C.sub.7)cycloalkenyl, (C.sub.6 -C.sub.14) bicycloalkyl, (C.sub.6 -C.sub.14) bicycloalkenyl, and aryl-fused systems containing 8 to 15 carbon atoms, one ring of any of said aryl-fused systems being aromatic and the ring containing the carbon to which R.sup.2 and R.sup.3 are attached being non-aromatic, one of the carbons of said aromatic ring being optionally replaced by sulfur or oxygen, one or more carbons of said non-aromatic ring being optionally replaced by sulfur or oxygen, one or two carbons of said cycloalkyl or bicycloalkyl groups being optionally replaced by sulfur or oxygen, and said cyclic or bicyclic system being optionally substituted with one to five substituents independently selected from the group consisting of phenyl, substituted phenyl, (C.sub.1 -C.sub.6) alkyl and A, with the proviso that one and only one of said substituents is A, and one and only one of said substituents is phenyl or substituted phenyl, said substituted phenyl being substituted with one or more substituents independently selected from the group consisting of (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) alkylthio, halogen and trifluoromethyl;
• and R.sup.4 is hydrogen, XR.sup.10 or A;
• with the proviso that when R.sup.1 is a group of the formula XXVI wherein G is nitrogen and wherein neither R.sup.5, R.sup.6 nor R.sup.15 is NR.sup.19 R.sup.20, (C.sub.1 -C.sub.6)alkylthio, (C.sub.5 -C.sub.7)cycloalkylthio, phenyl(C.sub.1 -C.sub.6) alkylthio, phenylthio or heteroalkylthio R.sup.2 and R.sup.3 together with the carbon to which they are attached, do not form a (C.sub.3 -C.sub.7) cycloalkyl ring containing only carbon atoms;
• A is a hydrocarbon containing 4 to 16 carbons and 0, 1 or 2 double bonds;
• X is O, S, SO, SO.sub.2, NH, NR.sup.23 CO or NSO.sub.2 R.sup.24, wherein R.sup.23 is hydrogen or (C.sub.1 -C.sub.6)alkyl and R.sup.24 is (C.sub.1 -C.sub.6)alkyl, phenyl or (C.sub.1 -C.sub.3) alkyl-phenyl;
• R.sup.5, R.sup.6, and R.sup.15 are each independently selected from the group consisting of hydrogen, halogen, (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) haloalkyl, (C.sub.1 -C.sub.6) alkoxy, (C.sub.1 -C.sub.6) alkylthio, (C.sub.3 -C.sub.7) cycloalkylthio, phenyl (C.sub.1 -C.sub.6) alkylthio, substituted phenylthio, heteroarylthio, heteroaryloxy, and NR.sup.19 R.sup.20, wherein R.sup.19 and R.sup.20 are the same or different and are selected from the group consisting of hydrogen, (C.sub.1 -C.sub.6) alkyl, phenyl, substituted phenyl, (C.sub.1 -C.sub.6) acyl, aroyl, and substituted aroyl, wherein said substituted phenyl and substituted aroyl groups are substituted with one or more substituents independently selected from the group consisting of (C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) alkoxy, (C.sub.1 -C.sub.6) alkylthio, halogen and trifluoromethyl, or R.sup.19 and R.sup.20, together with the nitrogen to which they are attached, form a piperidine or morpholine ring;
• R.sup.10 is selected from the group consisting of (C.sub.4 -C.sub.12) cycloalkyl, (C.sub.4 -C.sub.12) straight or branched alkyl, (C.sub.4 -C.sub.12) cycloalkyl-(C.sub.1 -C.sub.6) alkyl, phenyl-(C.sub.1 -C.sub.6) alkyl, substituted phenyl-(C.sub.1 -C.sub.6) alkyl, (C.sub.1 -C.sub.6) alkyl-phenyl, (C.sub.1 -C.sub.6) alkyl-substituted phenyl, substituted thiazoles, substituted benzothiazoles, and substituted pyridines;
• wherein the substituents on the substituted phenyl, substituted thiazoles, substituted benzothiazoles and substituted pyridines are selected from the group consisting of (C.sub.1 -C.sub.6) alkoxy, (C.sub.1 -C.sub.6) alkylthio, (C.sub.1 -C.sub.6) alkyl, halo and trifluoromethyl;
• G is selected from the group consisting of nitrogen and carbon, and with the proviso that when G is nitrogen, the group XXVI is attached to the nitrogen of formula I at the 4 or 5 position of the pyrimidine ring (designated by a and b);
• and R.sup.17 and R.sup.18 are each independently selected from the group consisting of (C.sub.4 -C.sub.12) straight or branched alkyl, phenyl-(C.sub.1 -C.sub.6) alkyl, and (C.sub.1 -C.sub.6) alkylphenyl-(C.sub.1 -C.sub.6) alkyl;
• or a pharmaceutically acceptable salt of said compound.