Macrocycles incorporating quinazolinones

A compound of structural formula I:

• ##STR36## or a pharmaceutically acceptable salt thereof, wherein:
• Q is --N(R.sup.4)-- or ##STR37## R.sup.1 is a) aryl,
• b) C.sub.1-6 alkyl or C.sub.2-5 alkenyl, each of which is unsubstituted or substituted with aryl, C.sub.3-7 cycloalkyl, halo, CF.sub.3 or CF.sub.2 CF.sub.3,
• c) C.sub.3-7 cycloalkyl or
• d) perfluoro C.sub.1-4 alkyl;
• R.sup.2 is C.sub.1-6 alkyl or F;
• R.sup.3 is
• a) H,
• b) C.sub.1-6 alkyl,
• c) aryl,
• d) heteroaryl,
• e) C.sub.1-4 alkylamino,
• f) di(C.sub.1-4 alkyl)amino,
• g) (C.sub.1-6 alkoxy)CH.sub.2 --,
• h) (C.sub.1-6 alkylthio)CH.sub.2 --,
• i) C.sub.1-6 alkylthio,
• j) (C.sub.1-6 alkyl).sub.2 NCH.sub.2 --,
• k) C.sub.2-6 alkenyl,
• l) C.sub.2-6 alkynyl,
• m) aryl C.sub.1-6 alkyl-, or
• n) C.sub.3-7 cycloalkyl;
• R.sup.4 is
• a) --COR.sup.6 wherein R.sup.6 is
• 1) aryl,
• 2) heteroaryl,
• 3) morpholinyl,
• 4) piperazinyl,
• 5) N-(C.sub.1-4 alkyl)-piperazinyl,
• 6) N-(aryl)piperazinyl
• 7) C.sub.1-6 alkyl, or
• 8) substituted C.sub.1-6 alkyl or ##STR38## b) --CO.sub.2 R.sup.7 wherein R.sup.7 is 1) C.sub.1-6 alkyl
• 2) substituted C.sub.1-6 alkyl,
• 3) aryl, or
• 4) heteroaryl;
• c) --CONR.sup.7 R.sup.8 wherein R.sup.8 is C.sub.1-4 alkyl or H;
• d) C.sub.1-6 alkyl,
• e) substituted C.sub.1-6 alkyl,
• f) aryl, or
• g) heteroaryl;
• h) hydrogen,
• M is --N.dbd. or ##STR39## wherein R.sup.9 is H, C.sub.1-3 alkyl, F or CF.sub.3 ;
• K is --CO-- or --SO.sub.2 --;
• L is --CO-- or --SO.sub.2 --
• A is --CO--, or --CH.sub.2 --;
• D is --CH.sub.2 --, --O--, --NR.sup.8 or a single bond;
• E is (CH.sub.2).sub.b wherein b=0-6;
• G is (a) --C(R.sup.5).sub.2 --, wherein the R.sup.5 groups are the same or different and R.sup.5 is C.sub.1-6 alkyl, substituted C.sub.1-6 alkyl, aryl, heteroaryl or hydrogen
• (b) --O--,
• (c) --S(O).sub.p -- wherein p is 0-2,
• (d) --CH.dbd.CH--,
• (e) --CO--,
• (f) --NR.sup.5 CO--,
• (g) --NHSO.sub.2 NH--,
• (h) --CO.sub.2 --,
• (i) --OCONH--,
• (j) --NHCO.sub.2 --,
• (k) --NR.sup.7,
• (l) aryl,
• (m) heteroaryl, or
• (n) single bond;
• J is
• (a) (CH.sub.2).sub.r, wherein r is 1-8, or
• (b) single bond
• with the provisos that:
• 1) if A is CO then R.sup.4 is C.sub.1-6 alkyl, substituted C.sub.1-6 alkyl, aryl, heteroaryl or H;
• 2) if A is CO and D is O or NR.sup.8 then:
• (a) E is (CH.sub.2).sub.n wherein n is 2-6;
• (b) E is CH.sub.2 and G is --C(R.sup.5).sub.2 --;
• or
• (c) E is a single bond and G is aryl or heteroaryl;
• 3) if A is --(CH.sub.2)--, then R.sup.4 is --COR.sup.6, --CO.sub.2 R.sup.7, --CONR.sup.7 R.sup.8 or H and D is --CH.sub.2 -- or a single bond;
• 4) if Q is piperazine then A is CO
• wherein:
• aryl denotes phenyl or naphthyl, which can be unsubstituted or substituted with C.sub.1-3 alkyl, C.sub.1-3 alkoxy, halo, or CF.sub.3 ;
• and
• heteroaryl means a 5- or 6-membered heteroaromatic comprising up to 3 heteroatoms selected from O, N and S selected from imidazole, pyrazole, triazole, thiazole, oxazole, thiadiazole, oxadiazole, oxathiazole, pyridine, pyrimidine, pyrazine, pyridazine, thiazine, wherein the heteroaromatic can be unsubstituted or substituted with one or two substituents selected from C.sub.1-3 alkyl, C.sub.1-3 alkoxy, halo or CF.sub.3.