Author: claimsbot

1. A composition comprising:
(a) at least one lipid modulating agent; and
(b) at least one substituted azetidinone compound or substituted \u03b1-lactam compound or salt or solvate thereof.
2. The composition according to claim 1, wherein the substituted azetidinone compound is represented by Formula (I):
or pharmaceutically acceptable salts or solvates thereof, wherein in Formula (I) above:
Ar1 and Ar2 are independently selected from the group consisting of aryl and R4-substituted aryl;
Ar3 is aryl or R5-substituted aryl;
X, Y and Z are independently selected from the group consisting of \u2014CH2\u2014, \u2014CH(lower alkyl)- and \u2014C(dilower alkyl)-;
R and R2 are independently selected from the group consisting of \u2014O6, \u2014O(CO)R5, \u2014O(CO)OR9 and\u2014O(CO)NR6R7 ;
R1 and R3 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 selected from 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;
R4 is 1-5 substituents independently selected from the group consisting of lower alkyl, \u2014OR6, \u2014O(CO)R6, \u2014O(CO)OR9, \u2014O(CH2)1-5OR6, \u2014O(CO)NR6R7, \u2014NR6R7, \u2014NR6(CO)R7, \u2014NR6(CO)OR9, \u2014NR6(CO)NR7R8, \u2014NR6SO2R9, \u2014COOR6, \u2014CONR6R7, \u2014COR,6, \u2014SO2NR6R7, S(O)0-2R9, \u2014O(CH2)1-10\u2014COOR6, \u2014O(CH2)1-10CONR6R7, -(lower alkylene)COOR6, \u2014CH\u2550CH\u2014COOR6, \u2014CF3, \u2014CN, \u2014NO2 and halogen;
R5 is 1-5 substituents independently selected from the group consisting of \u2014OR6, \u2014O(CO)R6, \u2014O(CO)OR9, \u2014O(CH2)1-5OR6, \u2014O(CO)NR6R7, \u2014NR6R7, \u2014NR6(CO)R7, \u2014NR6(CO)OR9, \u2014NR (CO)NR7R8, \u2014NR6 SO2R9, \u2014COOR6, \u2014CONR6R7, \u2014COR6, \u2014SO2NR6R7, S(O)0-2R9, \u2014O(CH2)1-10\u2014COOR6, \u2014O(CH2), 1-10CONR6R7, -(lower alkylene)COOR6 and \u2014CH\u2550CH\u2014COOR6;
R6, R7 and R8 are independently selected from the group consisting of hydrogen, lower alkyl, aryl and aryl-substituted lower alkyl; and
R9 is lower alkyl, aryl or aryl-substituted lower alkyl.
3. The composition according to claim 1, wherein the substituted azetidinone compound is represented by Formula (II) below:
or pharmaceutically acceptable salt or solvate thereof.
4. The composition according to claim 1, wherein the lipid modulating agent is selected from the group consisting of synthetic HDL, phospholipids, phospholipids in combination with HDL associated and biologically active peptides derived therefrom, reverse lipid transport (RLT) peptides, enzymes associated with HDL, and apo E, alone or formulated in combination with liposomes or emulsions.
5. The composition according to claim 1, wherein the lipid modulating agent is a synthetic HDL complex comprising recombinant apolipoprotein A-I Milano and 1-palmitoyl-2-oleoyl phosphatidyl choline complex.
6. A composition comprising: (a) at least one lipid modulating agent; and (b) a compound represented by Formula (II) below:
or pharmaceutically acceptable salt or solvate thereof.
7. A therapeutic combination comprising: (a) a first amount of at least one lipid modulating agent; and (b) a second amount of at least one substituted azetidinone compound or substituted \u03b2-lactam compound or pharmaceutically acceptable salt or solvate thereof, wherein the first amount and the second amount together comprise a therapeutically effective amount for the treatment or prevention of a vascular condition, diabetes, obesity or lowering a concentration of a sterol in plasma of a subject.
8. A pharmaceutical compositions for the treatment or prevention of a vascular condition, diabetes, obesity or lowering a concentration of a sterol in plasma of a subject, comprising a therapeutically effective amount of a composition or therapeutic combination of claim 1 and a pharmaceutically acceptable carrier.
9. A method of treating or preventing a vascular condition, diabetes, obesity or lowering a concentration of a sterol in plasma of a subject, comprising the step of administering to a mammal in need of such treatment an effective amount of a composition or therapeutic combination of claim 1.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A compound of Formula I:
wherein
L is (C5-C8)cycloalkyl; phenyl optionally substituted by 1-4 (C1-C4)alkyl; \u2014(CH2)n\u2014 where n is 1, 2, or 4-10; \u2014C(Rx)2\u2014; or \u2014CH2\u2014C(Rx)2\u2014CH2\u2014; where each Rx is independently OH, or \u2014CH2O-Sac;
each X is independently O, S, NH, triazole; or a direct bond;
each m is 0 or 1;
each R1 is independently H or (C1-C20)alkyl; and
each Amph is independently a moiety of Formula A:
wherein
Y is CH2 or a direct bond;
each R2, R3, and R4 is independently H, OH, or O-Sac; and
each Sac is independently a monosaccharide, disaccharide, or trisaccharide;
wherein the compound has at least 4 Sac groups.
2. The compound of claim 1 wherein each R1 is (C1-C20)alkyl.
3. The compound of claim 1 wherein Y is a direct bond.
4. The compound of claim 1 wherein at least two of R2, R3 and R3 are O-Sac and each Sac is a disaccharide.
5. The compound claim 1 wherein the compound is a compound of Formula III:
6. The compound claim 1 wherein the compound is a compound of Formula XII:
where each R2 is independently an oxygen linked monosaccharide, disaccharide, trisaccharide.
7. The compound claim 6 wherein the compound is:
8. The compound claim 1 wherein the compound is a compound of Formula XIII:
9. The compound claim 8 wherein the compound is:
10. The compound claim 1 wherein the compound is a compound of Formula XIV:
where each R2 is independently a monosaccharide, disaccharide, trisaccharide.
11. The compound claim 10 wherein the compound is:
12. A compound of Formula I:
Amph-X-L-X-Amph\u2003\u2003(I)
wherein
L is (C5-C8)cycloalkyl; phenyl optionally substituted by 1-4 (C1-C4)alkyl; \u2014(CH2)n\u2014 where n is 1-10; \u2014C(Rx)2\u2014; or \u2014CH2\u2014C(Rx)2\u2014CH2\u2014; where each Rx is independently H, OH, or \u2014CH2O-Sac;
each X is independently O, S, NH, CH2, triazole; or a direct bond; and
each Amph is independently a moiety of Formula A:
wherein
Y is CH2 or a direct bond;
each R2, R3, and R4 is independently H, OH, or O-Sac; and
each Sac is independently a monosaccharide, disaccharide, or trisaccharide;
wherein the compound has at least 4 Sac groups.
13. The compound claim 12 wherein the compound is a compound of Formula VII:
wherein each X is independently O, S, NH, CH2, or triazole; and n is \u22121, 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10.
14. The compound claim 13 wherein the compound is a compound of Formula VIII:
wherein each X is S, O, CH2, or
15. The compound of claim 1 wherein a plurality of the compounds form a micelle in water comprising about 6 to about 15 molecules of the compound.
16-20. (canceled)
21. A compound of Formula I:
where L is \u2014(CH2)n\u2014 where n is 1-10; (C5-C8)cycloalkyl; a phenyl diradical optionally substituted by 1, 2, 3, or 4 (C1-C4)alkyl groups; \u2014C(Rx)2\u2014; or \u2014CH2\u2014C(Rx)2\u2014CH2\u2014; where each Rx is independently H, OH, or \u2014CH2O-Sac;
each X is independently O, S, NH, CH2, triazole, or a direct bond;
each m is 0 or 1;
each R1 is independently (C5-C20)alkyl; and
each Amph is independently a moiety of Formula A:
wherein
Y is CH2 or a direct bond;
each R2, R3, and R4 is independently H, OH, or O-Sac; and

each Sac is independently an oxygen-linked monosaccharide, disaccharide, or trisaccharide where the compound of Formula I has at least 4 Sac groups.

1. A compound of Formula I:
wherein:
R1 is C6-10 aryl substituted with 1, 2, or 3 R5;
A is CH;
R2 is C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, C1-10 haloalkoxy, C6-10 aryl optionally substituted with 1, 2, or 3 R5, heteroaryl optionally substituted with 1, 2, or 3 R5, or arylalkyl optionally substituted with 1, 2, or 3 R5;
R3 and R3a are, independently, hydrogen, C1-10 alkyl or C1-10 haloalkyl;
R4 and R4a are, independently, hydrogen, C1-10 alkyl or C1-10 haloalkyl,
or
R4 and R4a together with the nitrogen atom through which they are attached, form a heterocyclic ring of 4 to 7 ring atoms, where one carbon ring atom may be optionally replaced with NR6, O, S, or SO2, and where any carbon ring atom may be optionally substituted with C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, or C1-10 haloalkoxy;
each R5 is independently halo, cyano, hydroxy, C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, C1-10 haloalkoxy, aryloxy optionally substituted with 1, 2, or 3 R7, amino, C1-10 alkylamino, C1-10 dialkylamino, C1-10 alkylsulfonyl, sulfamoyl, C1-10 alkylsulfamoyl or C1-10 dialkylsulfamoyl;
or
two adjacent R5 groups taken together equal methylenedioxy;
R6 is C1-10 alkyl or C1-10 haloalkyl;
R7 is halo, cyano, hydroxy, C1-10 alkyl, C1-10 haloalkyl, C1-10 alkoxy, C1-10 haloalkoxy, amino, C1-10 alkylamino, C1-10 dialkylamino, C1-10 alkylsulfonyl, sulfamoyl, C1-10 alkylsulfamoyl or C1-10 dialkylsulfamoyl;
provided that when R1 is unsubstituted phenyl, R2 is C6-10 aryl substituted with 1, 2, or 3 R5 or heteroaryl optionally substituted with 1, 2, or 3 R5;
or a pharmaceutically acceptable salt, enantiomer, or diastereoisomer thereof;
provided that the compound of Formula I is not:
5-(tert-butyl)-3\u2032,4\u2032-dichloro-3-(pyrrolidin-1-ylmethyl)-1,1\u2032-biphenyl-2-ol;
5-((3r,5r,7r)-adamantan-1-yl)-4\u2032-chloro-3-((dimethylamino)methyl)-1,1\u2032-biphenyl-2-ol;
5-(tert-butyl)-4\u2032-(dimethylamino)-3-((dimethylamino)methyl)-1,1\u2032-biphenyl-2-ol;
5-(tert-butyl)-3-((tert-butylamino)methyl)-4\u2032-chloro-1,1\u2032-biphenyl-2-ol;
3,3\u2032,5,5\u2032-tetrakis((diethylamino)methyl)-1,1\u2032-biphenyl-2,2\u2032-diol;
4,4\u2032\u2033-dichloro-5\u2032,5\u2033-bis(pyrrolidin-1-ylmethyl)-1,1\u2032:3\u2032,1\u2033:3\u2033,1\u2033-quaterphenyl-4\u2033,6\u2032-diol;
3,3\u2032,5,5\u2032-tetrakis(morpholinomethyl)-1,1\u2032-biphenyl-2,2\u2032-diol;
3,3\u2032-bis((diethylamino)methyl)-5,5\u2032-dimethoxy-1,1\u2032-biphenyl-2,2\u2032-diol;
or 3-((diethylamino)methyl)-5,5\u2032-dimethoxy-1,1\u2032-biphenyl-2,2\u2032-diol;

or a pharmaceutically acceptable salt, enantiomer, or diastereoisomer thereof.
2. The compound according to claim 1 wherein R3 and R3a are H.
3. The compound according to claim 1 wherein R4 is tert-butyl or 1-methylcyclobutyl and R4a is H.
4. The compound according to claim 1 wherein R2 is tert-butyl, C6-10 aryl optionally substituted with 1, 2, or 3 R5 or heteroaryl optionally substituted with 1, 2, or 3 R5.
5. The compound according to claim 1 wherein R2 is tert-butyl.
6. The compound according to claim 1 wherein R1 is phenyl substituted with 1, 2, or 3 groups of R5; R5 is halo, cyano, CF3 or OCF3.
7. The compound according to claim 1 wherein:
R1 is phenyl substituted with 1-3 groups of R5;
R3 and R3a are H;
R4 is tert-butyl or 1-methylcyclobutyl and R4a is H; and
R2 is tert-butyl, C6-10 aryl optionally substituted with 1, 2, or 3 R5 or heteroaryl optionally substituted with 1, 2, or 3 R5.
8. The compound according to claim 1 wherein:
R1 is phenyl substituted with 1, 2, or 3 groups of R5;
R3 and R3a are H;
R4 is tert-butyl and R4a is H; and
R2 is tert-butyl.
9. The compound according to claim 1 wherein said compound is:
5-(tert-butyl)-3-((tert-butylamino)methyl)-4\u2032-(trifluoromethoxy)-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-((isopropylamino)methyl)-4\u2032-(trifluoromethoxy)-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-(piperidin-1-ylmethyl)-4\u2032-(trifluoromethoxy)-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-((tert-butylamino)methyl)-3\u2032,5\u2032-bis(trifluoromethyl)-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-4(1-methylcyclobutyl)amino)methyl)-4\u2032-(trifluoromethoxy)-1,1\u2032-biphenyl-2-ol hydrochloride,
5-(tert-butyl)-3-((tert-butylamino)methyl)-3\u2032,4\u2032-dichloro-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-((tert-butylamino)methyl)-4\u2032-(trifluoromethyl)-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-((tert-butylamino)methyl)-4\u2032-chloro-3\u2032-(trifluoromethyl)-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-((tert-butylamino)methyl)-3\u2032-chloro-4\u2032-fluoro-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3\u2032,4\u2032-dichloro-3-(((1-methylcyclobutyl)amino)methyl)-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-((tert-butylamino)methyl)-4\u2032-chloro-3\u2032-fluoro-1,1\u2032-biphenyl-2-ol,
5-(tert-butyl)-3-((tert-butylamino)methyl)-3\u2032-chloro-4\u2032-(trifluoromethyl)-1,1\u2032-biphenyl-2-ol,
5\u2032-((tert-butylamino)methyl)-3\u2033,4,4\u2033-trichloro-1,1\u2032:3\u2032,1\u2033-terphenyl-4\u2032-ol,
5\u2032-((tert-butylamino)methyl)-3,3\u2033,4,4\u2033-tetrachloro-1,1\u2032:3\u2032,1\u2033-terphenyl-4\u2032-ol, or
5-(tert-butyl)-3-((tert-butyl(methyl)amino)methyl)-4\u2032-chloro-3\u2032-(trifluoromethyl)-1,1\u2032-biphenyl-2-ol,

or a pharmaceutically acceptable salt thereof.
10. The compound according to claim 1 that is a compound of formula IA:
11. The compound according to claim 10, wherein R4 and R4a are, independently, hydrogen or C1-10 alkyl or R4 and R4a, together with the nitrogen atom through which they are attached, form a heterocyclic ring of 4 to 7 ring atoms.
12. The compound according to claim 10, wherein R1 is unsubstituted naphthyl.
13. The compound according to claim 10, wherein R1 is substituted with 1, 2, or 3 of R5, wherein each R5 is independently \u2014CF3, \u2014OCF3, \u2014SO2C1-6alkyl, F, Cl, Br, \u2014Ophenyl.
14. The compound according to claim 1 that is a compound of formula IB:
wherein m is from 0 to 4 and t is from 0 to 3.
15. The compound according to claim 14, wherein m is 0.
16. The compound according to claim 14, wherein m is from 1 to 4.
17. The compound according to claim 14, wherein R4 and R4a are, independently, hydrogen or C1-10 alkyl or R4 and R4a, together with the nitrogen atom through which they are attached, form a heterocyclic ring of 4 to 7 ring atoms.
18. The compound according to claim 14, wherein t is 0.
19. The compound according to claim 14, wherein t is from 1 to 3.
20. The compound according to claim 19, wherein each R5 is independently \u2014CF3, \u2014OCF3, \u2014SO2C1-6alkyl, F, Cl, Br, or \u2014Ophenyl.
21. The compound according to claim 1 wherein R2 is pyridyl optionally substituted with 1, 2, or 3 R5.
22. The compound according to claim 1, wherein R2 is benzofuranyl optionally substituted with 1, 2, or 3 R5.
23. The compound according to claim 1, wherein R2 is \u2014OCF3 or \u2014Oalkaryl.
24. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.
25. A method of treating malaria in a patient comprising administering to the patient a compound according to claim 1.
26. The method according to claim 25 wherein the compound of Formula I is co-administered with at least one other anti-malarial agent that is Amodiaquine, Arteether, Arteflene, Artemether, Artemisinin, Artesunate, Atovaquone, Chloroquine, Clindamycin, Dihydroartemisinin, Doxycycline, Halofantrine, Lumefantrine, Mefloquine, Pamaquine, Piperaquine, Primaquine, Proguanil, Pyrimethamine, Pyronaridine, Quinine, Tafenoquine, or a combination thereof.

The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.

1. A vacuum switchgear comprising:
a pair of vacuum switches disposed in a vacuum container, each having a movable contact and a fixed contact
wherein the movable contact and the fixed contact being covered with an insulating cylinder,
wherein the movable contacts move to a closed position, an open position and a disconnecting position, and
wherein the movable contacts are connected to an operator via an air insulated operating rod disposed in air.
2. The vacuum switchgear according to claim 1, further comprising: a vacuum earthing switch having contacts that separate and close in vacuum of another vacuum container,
wherein the vacuum switches and the earthing switch are molded with resin to unite the vacuum containers of the vacuum switches.
3. The vacuum switchgear according to claim 2,
wherein the movable contacts of the vacuum switches and the movable contact of the earthing switch move in substantially a parallel direction.
4. The vacuum switchgear according to claim 2,
wherein the vacuum switches, the earthing switch and a voltage detector for detecting the circuit voltage are molded with resin to unite them.
5. The vacuum switchgear according to claim 2,
wherein the fixed contact of one of the vacuum switches is connected to a bus via a first feeder, and the fixed contact of the other vacuum switch is connected to a cable head via a second feeder, and
wherein the first feeder and the second feeder are molded with resin together with the vacuum switches and the earthing switch.
6. The vacuum switchgear according to claim 1,
wherein both of the movable contacts of the vacuum switches are connected to each other via a conductor to which a vacuum insulated operating rod is connected,
wherein the vacuum insulated operating rod is drawn out from the vacuum container via a bellows and is connected to the air insulated operating rod, and
wherein the air insulated operating rod is connected to an operating rod via an operator.
7. The vacuum switchgear according to claim 5,
wherein the fixed contact of the earthing switch is connected to the second feeder, and the movable contact is connected to an operating rod different from the insulating operating rod, the different operating rod being drawn out from the vacuum container of the earthing switch and connected to an insulating operating rod for the earthing switch via a bellows, and wherein the different operating rod for the earthing switch is connected to the operator for the vacuum switches.
8. The vacuum switchgear according to claim 1,
wherein a distance between electrodes at disconnection position is set to be larger than that the open position.
9. The vacuum switchgear according to claim 1,
wherein the vacuum switches each has functions of a load breaking switch and a vacuum circuit breaker.