Acid-group-substituted diphenylazetidinones, process for their preparation, medicaments comprising these compounds, and their use
View Patent ↗One embodiment of the invention relates to compounds of the formula I: in which R1, R2, R3, R4, R5 and R6 have the meanings given in the specification. Other embodiments of the invention relate to physiologically acceptable salts of the compounds of formula 1, to processes for their preparation and to medicaments comprising these compounds. The compounds of the invention are suitable for use, for example, as hypolipidemics.
1. A compound of the formula I,
wherein
R1, R2, R3, R4, R5, and R6, independently of one another, are chosen from:
LAG; or
(C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units; or
(C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units;
and wherein at least one carbon atom of the alkyl radical is replaced by a radical chosen from: —S(O) m — (wherein m=0–2), —O—, —(C═O)—, —(C═S)—, —CH═CH—, —C≡C—, —N((C 1 –C 6 )-alkyl)-, —N(phenyl), —N((C 1 –C 6 )-alkyl-phenyl)-, —N(CO—(CH 2 ) 1-10 —COOH)— and —NH—; or
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 2 –C 6 )-alkenyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—((C 1 –C 6 )-alkyl, S—(CH 2 ) n -phenyl, SO—(C 1 –C)-alkyl, SO—(CH 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(C 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO 2 —CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
wherein (LAG) is-(CH 2 ) 1-10 —SO 3 H; —(CH 2 ) 0-10 —P(O)(OH) 2 , —(CH 2 ) 0-10 —O—P(O(OH) 2 , or —(CH 2 ) 0-10 —COOH and wherein q is 1–5; and
wherein at least one of the radicals R1 to R6 must have the meaning:
LAG; or
(C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units; or
(C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units; and
wherein at least one carbon atom of the alkyl radical is replaced by a radical chosen from: —S(O) m — (wherein m=0–2), —O—, —C═O)—, —(C═S)—, —CH═CH—, —C≡C—, —N((C 1 –C 6 )-alkyl)-, —N(phenyl)-, —N((C 1 –C 6 )-alkyl-phenyl)-, —N(CO—(CH 2 ) 1-10 —COOH)— and —NH—,
or a pharmaceutically acceptable salt thereof, in any stereoisomeric form, or a mixture of any such compounds in any ratio;
with the proviso that the compound is not 2-{[4-(4-{1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetidin-2-yl}phenoxy)butyl]methylamino}ethanesulfonic acid, or a compound wherein the radicals R1–R6 have the meaning —O—(CH 2 ) 1-10 —COOH, (C 1 –C 6 )-alkylene-COOH or —COOH.
2. A compound as claimed in claim 1 ,
wherein
R2, R4, R5, and R6, independently of one another, are chosen from:
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 2 –C 6 )-alkenyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(CH 2 ) n -phenyl, SO—(C 1 –C 6 )-alkyl, SO—(CH 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO 2 —CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CCNH 2 ;
R1 and R3, independently of one another, are chosen from:
LAG; or
(C 1 –C 30 )-alkylene-(LAG); or
(C 1 –C 30 )-alkylene-(LAG), wherein at least one carbon atom of the alkylene radical is replaced by —O—, —C═O)—, —N(CH 3 )— or NH—; or
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 2 –C 6 )-alkenyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(C 2 ) n -phenyl, SO—(C 1 –C 6 )-alkenyl, SO—(C 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6 and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO 2 —CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
wherein (LAG) is —(CH 2 ) 1-10 —SO 3 H; —(CH 2 ) 0-10 —P(O)(OH) 2 , —(CH 2 ) 0-10 —O—P(O)(OH) 2 , or —(CH 2 ) 0-10 —COOH;
wherein at least one of the radicals R1 or R3 must have the meaning:
LAG; or
(C 1 –C 30 )-alkylene-(LAG); or
(C 1 –C 30 )-alkylene-(LAG), wherein at least one carbon atom of the alkylene radical is replaced by —O—, —(C═O)—, —N(CH 3 )— or —NH—.
3. A compound as claimed in claim 1 ,
wherein
R2, R4, R5, and R6, independently of one another, are chosen from:
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH( 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkenyl, (C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(C 2 ) n -phenyl, SO—(C 1 –C 6 )-alkyl, SO—(C 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6 and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO 2 —CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
R1 and R3, independently of one another, are chosen from:
—(CH 2 ) 0-1 —Y—W—Y′—W′-(LAG); or
—(CH 2 ) 0-1 —Y—W—(C 1 — C 25 )-alkylene-Y′—W′-(LAG); or
—(CH 2 ) 0-1 —Y—W—(C 1 — C 25 )-alkylene-Y′—W′-(LAG), wherein at least one carbon atom of the alkylene radical is replaced by —O—; or
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 2 –C 6 )-alkenyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, S—(C 2 ) n -phenyl, SO—(C 1 –C 6 )-alkenyl, SO—(CH 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, CI, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, CI, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO 2 —CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
wherein
Y, W, Y′W′, independently of one another, are chosen from: NH, NCH 3 , C═O, O, a bond, and —S(O) m , wherein m=0–2;
or Y—W together represent a bond;
or Y′—W′ together represent a bond; and
wherein (LAG) is chosen from:-(CH 2 ) 1-10 —SO 3 H, —(CH 2 ) 0-10 —P(O)(OH) 2 , (CH 2 ) 0-10 —O—P(O)(OH) 2 , and —(CH 2 ) 0-10 —COOH; and
wherein at least one of the radicals R1 or R3 must have the meaning:
—(CH 2 ) 0-1 —Y—W—Y′—W′-(LAG); or
—(CH 2 ) 0-1 —Y—W—(C 1 — C 25 )-alkylene-Y′—W′-(LAG), or
—(CH 2 ) 0-1 —Y—W—(C 1 — C 25 )-alkylene-Y′—W′-(LAG), wherein at least one carbon atom of the alkylene radical is replaced by —O—.
4. A compound as claimed in claim 1 , wherein (LAG) is —(CH 2 ) 0-10 —COOH or —(CH 2 ) 1-10 —SO 3 H.
5. A pharmaceutical composition, comprising an effective amount of at least one compound as claimed in claim 1 .
6. A process for preparing a pharmaceutical composition comprising at least one compound as claimed in claim 1 , comprising mixing the at least one compound with a pharmaceutically acceptable carrier and bringing this mixture into a form suitable for administration.
7. A method for treating hyperlipidemia, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 1 .
8. A method for lowering the serum cholesterol concentration, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 1 .
9. A method for treating arteriosclerotic manifestations, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 1 .
10. A method for treating a patient afflicted with insulin resistance, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 1 .
11. A compound of the formula I,
wherein
R1, R2, R3, R4, R5, and R6, independently of one another, are chosen from:
LAG; or
(C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units; or
(C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units;
wherein at least one carbon atom of the alkyl radical is replaced by a radical chosen from: —S(O) m — (wherein m=0–2), —C═O)—, —(O═S)—, —CH═CH—, —C≡C—, —N((C 1 –C 6 )-alkyl)-, —N(phenyl), —N((C 1 –C 6 )-alkyl-phenyl)-, —N(CO—(CH 2 ) 1-10 —COOH)— and —NH—; or
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkenyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(C 2 ) n -phenyl, SO—(C 1 –C 6 )-alkyl, SO—(C 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO 2 —CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
wherein (LAG) is —(CH 2 ) 0-10 —SO 3 H; —(CH 2 ) 0-10 —P(O)(OH) 2 , —(CH 2 ) 0-10 —O—P(O)(OH) 2 , or —(CH 2 ) 0-10 —COOH and wherein q is 1–5; and
wherein at least one of the radicals R1 to R6 must have the meaning:
LAG; or
(C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units; or (C 1 –C 30 )-alkyl, wherein the (C 1 –C 30 )-alkyl is substituted by q LAG units; and
wherein at least one carbon atom of the alkyl radical is replaced by a radical chosen from: —S(O) m — (wherein m=0–2), —C═O)—, —(C═S)—, —CH═CH—, —C≡C—, —N((C 1 –C 6 )-alkyl)-, —N(phenyl)-, —N((C 1 –C 6 )-alkyl-phenyl)- , —N(CO—(CH 2 ) 1-10 —COOH)— and —NH—;
or a pharmaceutically acceptable salt thereof, in any stereoisomeric form, or a mixture of any such compounds in any ratio;
with the proviso that the compound is not 2-{[4-(4-{1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-oxoazetid in-2-yl}phenoxy)butyl]methylamino}ethanesulfonic acid, or a compound wherein the radicals R1–R6 have the meaning —O—(CH 2 ) 1-10 —COOH, (C 1 –C 6 )-alkylene-COOH or —COOH.
12. A compound as claimed in claim 11 ,
wherein
R2, R4, R5, and R6, independently of one another, are chosen from:
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 2 –C 6 )-alkenyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(=NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(C 2 ) n -phenyl, SO—(C 1 –C 6 )-alkyl, SO—(C 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO 2 —CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
R1 and R3, independently of one another, are chosen from:
LAG; or
(C 1 –C 30 )-alkylene-(LAG); or
(C 1 –C 6 )-alkylene-(LAG), wherein at least one carbon atom of the alkylene radical is replaced by —(C═O)—, —N(CH 3 )— or —NH—; or
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CCN[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkenyl, (C 1 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(C 2 )-phenyl, SO—(C 1 –C 6 )-alkyl, SO—(C 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6 and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO—CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
wherein (LAG) is —(CH 2 ) 0-10 —SO 3 H; —(CH 2 ) 0-10 —P(O)(OH) 2 , —(CH 2 ) 0-10 —O—P(O)(OH) 2 , or —(CH 2 ) 0-10 —COOH;
wherein at least one of the radicals R1 or R3 must have the meaning:
LAG; or
(C 1 –C 30 )-alkylene-(LAG); or
(C 1 –C 30 )-alkylene-(LAG), wherein at least one carbon atom of the alkylene radical is replaced by —(C═O)—, —N(CH 3 )—or —NH—.
13. A compound as claimed in claim 11 ,
wherein
R2, R4, R5, and R6, independently of one another, are chosen from:
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 2 –C 6 )-alkenyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
C(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(C 2 ) n -phenyl, SO—((C 1 –C 6 )-alkyl, SO—(CH 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6 and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO—CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
R1 and R3, independently of one another, are chosen from:
—(CH 2 ) 0-1 —Y—W—Y′—W′-(LAG); or
—(CH 2 ) 0-1 —Y—W—(C 1 — C 25 )-alkylene-Y′—W′-(LAG);or
H, F, Cl, Br, I, CF 3 , NO 2 , N 3 , CN, COO(C 1 –C 6 )-alkyl, CONH 2 , CONH(C 1 –C 6 )-alkyl, CON[(C 1 –C 6 )-alkyl] 2 , (C 1 –C 6 )-alkyl, (C 2 –C 6 )-alknyl, (C 2 –C 6 )-alkynyl, or O—(C 1 –C 6 )-alkyl, wherein the alkyl radical is unsubstituted or at least one hydrogen in the alkyl radical is replaced by fluorine; or
O(═NH)(NH 2 ), PO 3 H 2 , SO 3 H, SO 2 —NH 2 , SO 2 NH(C 1 –C 6 )-alkyl, SO 2 N[(C 1 –C 6 )-alkyl] 2 , S—(C 1 –C 6 )-alkyl, S—(C 2 )-phenyl, SO—(C 1 –C 6 )-alkyl, SO—(C 2 ) n -phenyl, SO 2 —(C 1 –C 6 )-alkyl, or SO 2 —(CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl radical is unsubstituted or substituted one or two times, each substituent chosen independently from: F, Cl, Br, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, and NH 2 ; and
NH 2 , NH—(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , NHCO(C 1 –C 6 )-alkyl, phenyl, or O—CH 2 ) n -phenyl, wherein n=0–6, and wherein the phenyl ring is unsubstituted or substituted one, two, or three times, each substituent chosen independently from: F, Cl, Br, I, OH, CF 3 , NO 2 , CN, OCF 3 , O—(C 1 –C 6 )-alkyl, (C 1 –C 6 )-alkyl, NH 2 , NH(C 1 –C 6 )-alkyl, N((C 1 –C 6 )-alkyl) 2 , SO—CH 3 , COOH, COO—(C 1 –C 6 )-alkyl, and CONH 2 ;
wherein
Y, W, Y′W′, independently of one another, are chosen from: NH, NCH 3 ,
C═O, a bond, and S(O) m , wherein m=0–2;
or Y—W together represent a bond;
or Y′—W′ together represent a bond; and
wherein (LAG) is chosen from: —(CH 2 ) 0-10 —SO 3 H, —(CH 2 ) 0-10 —P(O)(OH) 2 , (CH 2 ) 0-10 —O—P(O)(OH) 2 , and —(CH 2 ) 0-10 —COOH; and
wherein at least one of the radicals R1 or R3 must have the meaning:
—(CH 2 ) 0-10 —Y—W—Y′—W′-(LAG); or
—(CH 2 ) 0-1 —Y—W—(C 1 — C 25 )-alkylene-Y′—W′-(LAG).
14. A compound as claimed in claim 11 , wherein (LAG) is —(CH 2 ) 0-10 —COOH or —(CH 2 ) 0-10 —SO 3 H.
15. A pharmaceutical composition, comprising an effective amount of at least one compound as claimed in claim 11 .
16. A process for preparing a pharmaceutical composition comprising at least one compound as claimed in claim 11 , comprising mixing the at least one compound with a pharmaceutically acceptable carrier and bringing this mixture into a form suitable for administration.
17. A method for treating hyperlipidemia, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 11 .
18. A method for lowering the serum cholesterol concentration, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 11 .
19. A method for treating arteriosclerotic manifestations, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 11 .
20. A method for treating a patient afflicted with insulin resistance, comprising administering to a patient in need thereof an effective amount of at least one compound as claimed in claim 11 .