Claims
- 1. A compound of the formula
- R.sup.1 --A--(W).sub.a --X--(CH.sub.2).sub.b --(Y).sub.c --B--Z--COOR(I)
- in which
- A is ##STR3## B is ##STR4## W is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.dbd.CH--CH.sub.2 --, --(CH.sub.2).sub.3 --, --CH.sub.2 CH(CH.sub.3)--, --COCH.sub.2 --, --CH(OH)CH.sub.2 -- or --CH.sub.2 COCH.sub.2 --;
- X is --CONR.sup.2 --, --NR.sup.2 CO--, --SO.sub.2 NR.sup.2 -- or --NR.sup.2 SO.sub.2 --;
- Y is --CH.sub.2 CH.sub.2 --, --CH.sub.2 CH.sub.2 O--, --OCH.sub.2 --, --CH(CH.sub.3)CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH--, --C(Q.sup.1, Q.sup.2)--CO(CH.sub.2).sub.4 --, --CH.sub.2 --, --CH.sub.2 CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)CH.sub.2 CH.sub.2 --, --CH.sub.2 COCH.sub.2 --, --C(Q.sup.1,Q.sup.2)--CH(OH)--, --C(Q.sup.1,Q.sup.2)-- CH(SSCH.sub.3)--, --CH(CH.sub.2 OH)CH.sub.2 or --CH(COOR)CH.sub.2 --, wherein the carbonyl groups may be in the form of oxime, oxime ether, ketal or thioketal or enol ether and the hydroxyl groups may be in the form of lower alkyl ether, di(lower alkyl)amino-lower-alkyl ether or of ester of lower alkanecarboxylic acids;
- Z is --OCH.sub.2 --, --NR.sup.6 CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)CH.sub.2 --, --CH.sub.2 --, --CH.dbd.CH-- or --C(CH.sub.3).dbd.CH--;
- R is hydrogen, lower alkyl, phenyl or phenyl-lower alkyl;
- Q.sup.1 and Q.sup.2 are hydrogen or lower alkyl or form, together with the C atom to which they are bonded, a 3- to 6-membered saturated ring;
- R.sup.1 is amidino or guanidino;
- R.sup.2 is hydrogen, lower alkyl, phenyl-lower-alkyl, phenyl-lower-alkyl which is substituted in the phenyl moiety by amino, amidino or --COOR, or a radical --CH.sub.2 COOR or --Y--B--X--COOR;
- R.sup.3 is hydrogen, lower alkyl, lower alkoxy, halogen, lower carbalkoxy, amino, lower alkylamino, di-lower-alkylamino or amidino;
- R.sup.4 is hydrogen, lower alkyl, lower alkoxy, halogen, lower carbalkoxy, amino, lower alkylamino, di-lower-alkyl-amino or a radical --Z--COOR or --CH.dbd.CH(CH.sub.2).sub.n COOR;
- R.sup.6 is hydrogen, lower alkyl or benzyl;
- n is an integer of 0-4;
- a, c and d each are 0 or 1;
- b is an integer of 0-2, where a and b are 0 when c is 1, and c is 0 when a or b is different from 0;
- or the physiologically acceptable salts thereof.
- 2. The compound according to claim 1 having the formula
- R.sup.1l --A--X--Y--B--Z--COOR (Ia),
- wherein R.sup.1, A, X, Y, B, Z, and R are as defined in claim 1.
- 3. The compound according to claim 1 having the formula
- R.sup.1 --A--W--X--(CH).sub.b --B--Z--COOR (Ib)
- wherein R.sup.1, A, W, X, b, B, Z, and R are as defined in claim 1.
- 4. The compound of claim 2 wherein Y is --CH.sub.2 CH.sub.2 --, --CH.sub.2 CH.sub.2 O--, --CH(CH.sub.3)CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH--, --CH.sub.2 CO--, --CH.sub.2 --, --CH.sub.2 CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)CH.sub.2 CH.sub.2 --, --CH.sub.2 COCH.sub.2 --, --CH.sub.2 CHOH--, --CH(CH.sub.2 OH)CH.sub.2 -- or --CH(COOR)CH.sub.2 --, wherein the carbonyl groups may be in the form of oxime, ketal or thioketal or enol ether and the hydroxyl groups may be in the form of lower alkyl ether or of ester of lower alkanecarboxylic acids.
- 5. The compound of claim 4 wherein R.sup.1 is amidino.
- 6. The compound of claim 5 wherein X is --CONR.sup.2 --.
- 7. The compound of claim 6 wherein Z is --CH(CH.sub.2)CH.sub.2 -- or --CH(CH.sub.3).dbd.CH--.
- 8. The compound of claim 7 wherein Z is --CH(CH.sub.3).dbd.CH--.
- 9. The compound of claim 8 wherein Y is --CH(CH.sub.2)CH.sub.2 --.
- 10. The compound of claim 9 wherein R is hydrogen or lower alkyl.
- 11. The compound of claim 10, ethyl (E)-5-[(RS)-2-(p-amidinobenzamido)propyl]-.beta.-methyl-2-thiophene-acrylate.
- 12. The compound of claim 10, (E)-5-[(RS)-2-(p-amidinobenzamido)propyl]-.beta.-methyl-2-thiophene-acrylic acid.
- 13. The compound of claim 7 wherein Z is --CH(CH.sub.3)CH.sub.2 --.
- 14. The compound of claim 13 wherein Y is --CH (CH.sub.3)CH.sub.2 --.
- 15. The compound of claim 14 wherein R is hydrogen or lower alkyl.
- 16. The compound of claim 14 ethyl (RS)-5-[(RS)-2-(p-amidinobenzamido)propyl]-.beta.-methyl-2-thiophene-propionate.
- 17. The compound of claim 14, (RS)-5-[(RS)-2-(p-amidinobenzamido)propyl]-.beta.-methyl-2-thiophene-propionic acid.
- 18. A pharmaceutical composition comprising a compound of the formula
- R.sup.1 --A--(W).sub.a --X--(CH.sub.2).sub.b (Y).sub.c--B--Z--COOR(I)
- in which
- A is ##STR5## B is ##STR6## W is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.dbd.CH--CH.sub.2 --, --(CH.sub.2).sub.3 --, --CH.sub.2 CH(CH.sub.3)--, --COCH.sub.2 --, --CH(OH)CH.sub.2 -- or --CH.sub.2 COCH.sub.2 --;
- X is --CONR.sup.2 --, --NR.sup.2 CO--, --SO.sub.2 NR.sup.2 -- or --NR.sup.2 SO.sub.2 --;
- Y is --CH.sub.2 CH.sub.2 --, --CH.sub.2 CH.sub.2 O--, --OCH.sub.2 --, --CH (CH.sub.3)CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH--, --C(Q.sup.1, Q.sup.2)--CO(CH.sub.2).sub.d --, --CH.sub.2 --, --CH.sub.2 CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)CH.sub.2 CH.sub.2 --, --CH.sub.2 COCH.sub.2 --, --C(Q.sup.1,Q.sup.2)--CH(OH)--, --C(Q.sup.1,Q.sup.2)-- CH(SSCH.sub.3)--, --CH(CH.sub.2 OH)CH.sub.2 -- or --CH(COOR)CH.sub.2 --, wherein the carbonyl groups may be in the form of oxime, oxime ether, ketal or thioketal or enol ether and the hydroxyl groups may be in the form of lower alkyl ether, di(lower alkyl)amino-lower-alkyl ether or of ester of lower alkanecarboxylic acids;
- Z is --OCH.sub.2 --, --NR.sup.6 CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)CH.sub.2 --, --CH.sub.2 --, --CH.dbd.CH-- or --C(CH.sub.2).dbd.CH--;
- R is hydrogen, lower alkyl, phenyl or phenyl-lower alkyl;
- Q.sup.1 and Q.sup.2 are hydrogen or lower alkyl or form, together with the C atom to which they are bonded, a 3- to 6-membered saturated ring;
- R.sup.1 is amidino or guanidino;
- R.sup.2 is hydrogen, lower alkyl, phenyl-lower-alkyl, phenyl-lower-alkyl which is substituted in the phenyl moiety by amino, amidino or --COOR, or a radical --CH.sub.2 COOR or --Y--B--X--COOR;
- R.sup.3 is hydrogen, lower alkyl, lower alkoxy, halogen, lower carbalkoxy, amino, lower alkylamino, di-lower-alkylamino or amidino;
- R.sup.4 is hydrogen, lower alkyl, lower alkoxy, halogen, lower carbalkoxy, amino, lower alkylamino, di-lower-alkyl-amino or a radical --Z--COOR or --CH.dbd.CH(CH.sub.2).sub.n COOR;
- R.sup.6 is hydrogen, lower alkyl or benzyl;
- n is an integer of 0-4;
- a, c and d each are 0 or 1;
- b is an integer of 0-2, where a and b are 0 when c is 1, and c is 0 when a or b is different from 0; or the physiologically acceptable salts thereof; together with one or more excipients or carriers.
- 19. A method of treating thromboses, apoplexy, myocardial infarct, inflammations and arteriosclerosis comprising administering an effective amount of a compound of the formula
- R.sup.1 --A--(W).sub.a --X--(CH.sub.2).sub.b --(Y).sub.c --B--Z--COOR(I)
- in which
- A is ##STR7## B is ##STR8## W is --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --CH.dbd.CH--CH.sub.2 --, --(CH.sub.2).sub.3 --, --CH.sub.2 CH(CH.sub.3)--, --COCH.sub.2 --, --CH(OH)CH.sub.2 -- or --CH.sub.2 COCH.sub.2 --;
- W is --CONR.sup.2 --, --NR.sup.2 CO--, --SO.sub.2 NR.sup.2 -- or --NR.sup.2 SO.sub.2 --;
- Y is --CH.sub.2 CH.sub.2 --, --CH.sub.2 CH.sub.2 O--, --OCH.sub.2 --, --CH(CH.sub.3)CH.sub.2 --, --CH.dbd.CH--, --CH.sub.2 --CH.dbd.CH--, C(Q.sup.1, Q.sup.2)--CO(CH.sub.2).sub.d --, --CH.sub.2 --, --CH.sub.2 CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)CH.sub.2 CH.sub.2 --, --CH.sub.2 COCH.sub.2 --, --C(Q.sup.1,Q.sup.2)--CH(OH)--, --C(Q.sup.1, Q.sup.2)-- CH(SSCH.sub.3)--, --CH(CH.sub.2 OH)CH.sub.2 -- or --CH(COOR)CH.sub.2 --, wherein the carbonyl groups may be in the form of oxime, oxime ether, ketal or thioketal or enol ether and the hydroxyl groups may be in the form of lower alkyl ether, di(lower-alkyl)amino-lower-alkyl ether or of ester of lower alkanecarboxylic acids; is --OCH.sub.2 --, --NR.sup.6 CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH(CH.sub.3)CH.sub.2 --, --CH.sub.2 --, --CH.dbd.CH-- or --C(CH.sub.3).dbd.CH--;
- R is hydrogen, lower alkyl, phenyl or phenyl-lower alkyl;
- Q.sup.1 and Q.sup.2 are hydrogen or lower alkyl or form, together with the C atom to which they are bonded, a 3- to 6-membered saturated ring;
- R.sup.1 is amidino or guanidino;
- R.sup.2 is hydrogen, lower alkyl, phenyl-lower-alkyl, phenyl-lower-alkyl which is substituted in the phenyl moiety by amino, amidino or --COOR, or a radical --CH.sub.2 COOR or --Y--B--X--COOR;
- R.sup.3 is hydrogen, lower alkyl, lower alkoxy, halogen, lower carbalkoxy, amino, lower alkylamino, di-lower-alkylamino or amidino;
- R.sup.4 is hydrogen, lower alkyl, lower alkoxy, halogen, lower carbalkoxy, amino, lower alkylamino, di-lower-alkyl-amino or a radical -Z-COOR or --CH.dbd.CH(CH.sub.2).sub.n COOR;
- R.sup.6 is hydrogen, lower alkyl or benzyl;
- n is an integer of 0-4;
- a, c and d each are 0 or 1;
- b is an integer of 0-2, where a and b are 0 when c is 1, and c is 0 when a or b is different from 0;
- or the physiologically acceptable salts thereof.
Priority Claims (2)
Number |
Date |
Country |
Kind |
326/89 |
Jan 1989 |
CHX |
|
4069/89 |
Nov 1989 |
CHX |
|
Parent Case Info
This is a division of application Ser. No. 07/755,960, filed Sep. 6, 1991, now U.S. Pat. No. 5,256,812, which is a division of application Ser. No. 07/465,858, filed Jan. 16, 1990, now U.S. Pat. No. 5,084,466.
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Divisions (2)
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Number |
Date |
Country |
Parent |
755960 |
Sep 1991 |
|
Parent |
465858 |
Jan 1990 |
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