A pharmaceutical composition for the treatment or prevention of <?delete-start id="REI-00068" date="20020528" ?>athersclerosis<?delete-end id="REI-00068" ?>, <?insert-start id="REI-00069" date="20020528" ?>atherosclerosis <?insert-end id="REI-00069" unt of a compound of claim 17 in a pharmaceutically acceptable carrier. view more

A method of treating or preventing atherosclerosis or reducing plasma cholesterol levels comprising administering to a mammal in need of such treatment an effective amount of a compound of claim <?delete-start id="REI-00072" date="20110614" I-00072" ?>7. view more

<?insert-start id="REI-00074" date="20020528" ?>10. A compound comprising 1-(4-fluorophenyl)-3(R)-[3(S)-(4-fluorophenyl)-3-hydroxypropyl)]-4(S)-4-(hydroxyphenyl)-2-azetidinone or a pharmaceutically acceptable salt thereof.<?insert-end id="REI-00074" view more

<?insert-start id="REI-00075" date="20020528" ?>11. A compound represented by the formula:</claim-text> <chemistry id="CHEM-US-00052" num="00052"><img id="EMI-C00052" he="30.06mm" wi="62.82mm" file="USRE042461-20110614-C00052.TIF" alt="embedded view more

<?insert-start id="REI-00076" date="20020528" ?>12. A pharmaceutical composition for the treatment or prevention of atherosclerosis, or for the reduction of plasma cholesterol levels, comprising an effective amount of a compound according to claims cally acceptable carrier. view more

<?insert-start id="REI-00077" date="20020528" ?>13. A method of treating or preventing atherosclerosis or reducing plasma cholesterol levels comprising administering to a mammal in need of such treatment an effective amount of a compound according to end id="REI-00077" ?> view more

A pharmaceutical composition for the treatment or prevention of atherosclerosis, or for the reduction of plasma cholesterol levels, comprising an effective amount of a compound represented by the formula I ##STR56## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.1 and Ar.sup.2 are independently selected from the group consisting of aryl and R.sup.4 -substituted aryl; Ar.sup.3 is aryl or R.sup.5 -substituted aryl; X, Y and Z are independently selected from the group consisting of --CH.sub.2 --, --CH(lower alkyl)-- and --C(dilower alkyl)--; R and R.sup.2 are independently selected from the group consisting of --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9 and --O(CO)NR.sup.6 R.sup.7 ; R.sup.1 and R.sup.3 are independently selected from the group consisting of hydrogen, lower alkyl and aryl; q is 0 or 1; r is or 1; m, n and p are independently 0, 1, 2, 3 or 4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1, 2, 3, 4, 5 or 6; and provided that when p is 0 and r is 1, the sum of m, q and n is 1, 2, 3, 4 or 5; R.sup.4 is 1-5 substituents independently selected from the group consisting of lower alkyl, --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --(lower alkylene)COOR.sup.6, --CH.dbd.CH--COOR.sup.6, --CF.sub.3, --CN, --NO.sub.2 and halogen; R.sup.5 is 1-5 substituents independently selected from the group consisting of --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2)l 5OR.sup.6, --O(CO)N R.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --(lower alkylene)COOR.sup.6 and --CH.dbd.CH--COOR.sup.6 ; R.sup.6, R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen, lower alkyl, aryl and aryl-substituted lower alkyl; and R.sup.9 is lower alkyl, aryl or aryl-substituted lower alkyl; in combination with an HMG CoA reductase inhibitor in a pharmaceutically acceptable carrier. view more

A pharmaceutical composition of claim 1 wherein, in the compound of formula I, Ar.sup.1 is phenyl or R.sup.4 -substituted phenyl, wherein R.sup.4 is halogen; Ar.sup.2 is phenyl or R.sup.4 -substituted phenyl, wherein R.sup.4 is halogen or --OR.sup.6, wherein R.sup.6 is lower alkyl or hydrogen; Ar.sup.3 is R.sup.5 -substituted phenyl, wherein R.sup.5 is --OR.sup.6, wherein R.sup.6 is lower alkyl or hydrogen; X, Y, and Z are each --CH.sub.2 --; R.sup.1 and R.sup.3 are each hydrogen; R and R.sup.2 are each --OR.sup.6, wherein R.sup.6 is hydrogen; and the sum of m, n, p, q and r is 2, 3 or 4. view more

A composition of claim 1 wherein the HMG CoA reductase inhibitor is selected from the group consisting of lovastatin, pravastatin, fluvastatin, simvastatin and atorvastatin.

A composition of claim 1 wherein the compound of formula I is selected from the group consisting of rel 3(R)--(2(R)-hydroxy-2-phenylethyl)-4(R)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; rel 3(R)-(2(R)-hydroxy-2-phenylethyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(S)-(1(S)-hydroxy-3-phenylpropyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(S)-(1(R)-hydroxy-3-phenylpropyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(R)-(1(R)-hydroxy-3-phenylpropyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(R)-(3(R)-hydroxy-3-phenylpropyl)-1,4(S)-bis-(4-methoxyphenyl)-2-azetidinone; 3(R)-(3(S)-hydroxy-3-phenylpropyl)-1,4(S)-bis-(4-methoxyphenyl)-2-azetidinone; 4(S)-(4-hydroxyphenyl)-3(R)-(3(R)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; 4(S)-(4-hydroxyphenyl)-3(R)-(3(S)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; rel 3(R)-›3(RS)-hydroxy-3-›4-(methoxymethoxy)-phenyl!propyl!-1,4(S)-bis-(4-methoxyphenyl)-2-azetidinone; 1-(4-fluorophenyl)-3(R)-›3(S)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-(4-hydroxyphenyl)-2-azetidinone; 1-(4-fluorophenyl)-3(R)-›3(R)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-(4-hydroxyphenyl)-2-azetidinone; 4(S)-›4-(acetyloxy)phenyl!-3(R)-(3(R)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; 4(S)-›4-(acetyloxy)phenyl!-3(R)-(3(S)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; 1-(4-fluorophenyl)-3(R)-›3(S)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-›4-(phenylmethoxy)phenyl!-2-azetidinone; 3(R)-›3(R)-acetyloxy)-3-phenylpropyl!-1,4(S)-bis-(4-methoxy-phenyl)-2-azetidinone; 3(R)-›3(S)-acetyloxy)-3-phenylpropyl!-1,4(S)-bis-(4-methoxy-phenyl)-2-azetidinone; 3(R)-›3(R)-(acetyloxy)-3-(4-fluorophenyl)propyl!-4(S)-›4-(acetyloxy)-phenyl!-1-(4-fluorophenyl)-2-azetidinone; 3(R)-›3(S)-(acetyloxy)-3-(4-fluorophenyl)propyl!-4(S)-›4-(acetyloxy)-phenyl!-1-(4-fluorophenyl)-2-azetidinone; 3(R)-›3(R)-(acetyloxy)-3-(4-chlorophenyl)propyl!-4(S)-›4-(acetyloxy)phenyl!-1l-(4-chlorophenyl)-2-azetidinone; 3(R)-›3(S)-(acetyloxy)-3-(4-chlorophenyl)propyl!-4(S)-›4-(acetyloxy)phenyl!-1-(4-chlorophenyl)-2-azetidinone; and rel 1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-3(R)-(1(R)-hydroxy-3-phenylpropyl)-2-azetidinone. view more

A composition of claim 1 comprising a combination of 1-(4-fluorophenyl)-3(R)-›3(R)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-(4-hydroxyphenyl)-2-azetidinone and lovastatin, pravastatin, fluvastatin, simvastatin or atorvastatin.

A method of treating or preventing atherosclerosis or reducing plasma cholesterol levels comprising administering to a mammal in need thereof an effective amount of a compound represented by the formula I ##STR57## or a pharmaceutically acceptable salt thereof, wherein: Ar.sup.1 and Ar.sup.2 are independently selected from the group consisting of aryl and R.sup.4 -substituted aryl; Ar.sup.3 is aryl or R.sup.5 -substituted aryl; X, Y and Z are independently selected from the group consisting of --CH.sub.2 --, --CH(lower alkyl)-- and --C(dilower alkyl)--; R and R.sup.2 are independently selected from the group consisting of --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9 and --O(CO)NR.sup.6 R.sup.7 ; R.sup.1 and R.sup.3 are independently selected from the group consisting of hydrogen, lower alkyl and aryl; q is 0 or 1; r is 0 or 1; m, n and p are independently 0, 1, 2, 3 or 4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1, 2, 3, 4, 5 or 6; and provided that when p is 0 and r is 1, the sum of m, q and n is 1, 2, 3, 4 or 5; R.sup.4 is 1-5 substituents independently selected from the group consisting of lower alkyl, --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO) R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --(lower alkylene)COOR.sup.6, --CH.dbd.CH--COOR.sup.6, --CF.sub.3, --CN, --NO.sub.2 and halogen; R.sup.5 is 1-5 substituents independently selected from the group consisting of --OR.sup.6, --O(CO)R.sup.6, --O(CO)OR.sup.9, --O(CH.sub.2).sub.1-5 OR.sup.6, --O(CO)NR.sup.6 R.sup.7, --NR.sup.6 R.sup.7, --NR.sup.6 (CO)R.sup.7, --NR.sup.6 (CO)OR.sup.9, --NR.sup.6 (CO)NR.sup.7 R.sup.8, --NR.sup.6 SO.sub.2 R.sup.9, --COOR.sup.6, --CONR.sup.6 R.sup.7, --COR.sup.6, --SO.sub.2 NR.sup.6 R.sup.7, S(O).sub.0-2 R.sup.9, --O(CH.sub.2).sub.1-10 --COOR.sup.6, --O(CH.sub.2).sub.1-10 CONR.sup.6 R.sup.7, --(lower alkylene)COOR.sup.6 and --CH.dbd.CH--COOR.sup.6 ; R.sup.6, R.sup.7 and R.sup.8 are independently selected from the group consisting of hydrogen, lower alkyl, aryl and aryl-substituted lower alkyl; and R.sup.9 is lower alkyl, aryl or aryl-substituted lower alkyl; in combination with an effective amount of a cholesterol biosynthesis inhibitor selected from the group consisting of HMG CoA reductase inhibitors. view more

A method of claim 6 wherein, in the compound of formula I, Ar.sup.1 is phenyl or R.sup.4 -substituted phenyl, wherein R.sup.4 is halogen; Ar.sup.2 is phenyl or R.sup.4 -substituted phenyl, wherein R.sup.4 is halogen or --OR.sup.6, wherein R.sup.6 is lower alkyl or hydrogen; Ar.sup.3 is R.sup.5 -substituted phenyl, wherein R.sup.5 is --OR.sup.6, wherein R.sup.6 is lower alkyl or hydrogen; X, Y, and Z are each --CH.sub.2 --; R.sup.1 and R.sup.3 are each hydrogen; R and R.sup.2 are each --OR.sup.6, wherein R.sup.6 is hydrogen; and the sum of m, n, p, q and r is 2, 3 or 4. view more

A method of claim 6 wherein the HMG CoA reductase inhibitor is selected from the group consisting of lovastatin, pravastatin, fluvastatin, simvastatin and atorvastatin.

A method of claim 6 wherein the compound of formula I is selected from the group consisting of rel 3(R)-(2(R)-hydroxy-2-phenylethyl)-4(R)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; rel 3(R)-(2(R)-hydroxy-2-phenylethyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(S)-(1(S)-hydroxy-3-phenylpropyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(S)-(1(R)-hydroxy-3-phenylpropyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(R)-(1(R)-hydroxy-3-phenylpropyl)-4(S)-(4-methoxyphenyl)-1-phenyl-2-azetidinone; 3(R)-(3(R)-hydroxy-3-phenylpropyl)-1,4(S)-bis-(4-methoxyphenyl)-2-azetidinone; 3(R)-(3(S)-hydroxy-3-phenylpropyl)-1,4(S)-bis-(4-methoxyphenyl)-2-azetidinone; 4(S)-(4-hydroxyphenyl)-3(R)-(3(R)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; 4(S)-(4-hydroxyphenyl)-3(R)-(3(S)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; rel 3(R)-›3(RS)-hydroxy-3-›4-(methoxymethoxy)-phenyl!propyl!-1,4(S)-bis-(4-methoxyphenyl)-2-azetidinone; 1-(4-fluorophenyl)-3(R)-›3(S)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-(4-hydroxyphenyl)-2-azetidinone; 1-(4-fluorophenyl)-3(R)-›3(R)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-(4-hydroxyphenyl)-2-azetidinone; 4(S)-›4-(acetyloxy)phenyl!-3(R)-(3(R)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; 4(S)-›4-(acetyloxy)phenyl!-3(R)-(3(S)-hydroxy-3-phenylpropyl)-1-(4-methoxyphenyl)-2-azetidinone; 1-(4-fluorophenyl)-3(R)-›3(S)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-›4-(phenylmethoxy)phenyl!-2-azetidinone; 3(R)-›3(R)-acetyloxy)-3-phenylpropyl!-1,4(S)-bis-(4-methoxy-phenyl)-2-azetidinone; 3(R)-›3(S)-acetyloxy)-3-phenylpropyl!-1,4(S)-bis-(4-methoxy-phenyl)-2-azetidinone; 3(R)-›3(R)-(acetyloxy)-3-(4-fluorophenyl)propyl!-4(S)-›4-(acetyloxy)-phenyl!-1 -(4-fluorophenyl)-2-azetidinone; 3(R)-›3(S)-(acetyloxy)-3-(4-fluorophenyl)propyl!-4(S)-›4-(acetyloxy)-phenyl!-1-(4-fluorophenyl)-2-azetidinone; 3(R)-›3(R)-(acetyloxy)-3-(4-chlorophenyl)propyl!-4(S)-›4-(acetyloxy)phenyl!-1-(4-chlorophenyl)-2-azetidinone; 3(R)-›3(S)-(acetyloxy)-3-(4-chlorophenyl)propyl!-4(S)-›4-(acetyloxy)phenyl!-1-(4-chlorophenyl)-2-azetidinone; and rel 1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-3(R)-(1(R)-hydroxy-3-phenylpropyl)-2-azetidinone. view more

A method of claim 6 comprising administering a combination of 1-(4-fluorophenyl)-3(R)-›3(R)-(4-fluorophenyl)-3-hydroxypropyl)!-4(S)-(4-hydroxyphenyl)-2-azetidinone and lovastatin, pravastatin, fluvastatin, simvastatin or atorvastatin.