Claims
- 1. A bicyclic compound having a nucleus formed from two fused six-membered rings, A and B, represented by the formula (I), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof: the bicyclic nucleus of rings A and B is formula (17) below: R3 is an acidic group comprising a carboxylic acid radical; n is a number from 0 to 5; R0 is the same or different and is independently selected from the group consisting of hydrogen, alkyl, hydroxy, alkoxy, amino, substituted amino, halo, and ═O; the linking group —(L)— is selected from a group of from 1 to 4 chain atoms having the general formulae: where Z1, Z2, Z3, and Z4 are atoms independently selected from the group consisting of carbon, substituted carbon, nitrogen, substituted nitrogen, and oxygen; and Q is a basic group selected from the group consisting of piperidyl, amidinophenyl, amidophenyl, guanidinophenyl, and groups of the formula: wherein X is a halogen.
- 2. A compound of claim 1, wherein the carboxylic acid of the acidic group R3 is selected from the following formulae:
- 3. A compound of claim 1, wherein the carboxylic acid of the acidic group R3 is selected from the following formulae:
- 4. The compound of claim 1, wherein the basic group is amidinophenyl or guanidinophenyl.
- 5. The compound of claim 1, wherein the halo substituent of the basic group is fluoro.
- 6. The compound of claim 1, wherein the linking group is selected from the formulae:
- 7. A prodrug bicyclic compound having a nucleus formed from two fused six-membered rings, A and B, represented by the formula (I), or a pharmaceutically acceptable salt or solvate thereof: the bicyclic nucleus of rings A and B is formula (17) below: R3 is an acidic group comprising an ester derivative of a carboxylic acid radical; n is a number from 0 to 5; R0 is the same or different and is independently selected from the group consisting of hydrogen, alkyl, hydroxy, alkoxy, amino, substituted amino, halo, and ═O; the linking group —(L)— is selected from a group of from 1 to 4 chain atoms having the general formulae: where Z1, Z2, Z3, and Z4 are atoms independently selected from the group consisting of carbon, substituted carbon, nitrogen, substituted nitrogen, and oxygen; and Q is an acylated basic group wherein the basic group is selected from the group consisting of piperidyl, amidinophenyl, amidophenyl, guanidinophenyl, and groups of the formula: wherein X is a halogen.
- 8. The compound of claim 7, wherein the ester derivative of the carboxylic acid radical is an ester selected from the group consisting of methyl, ethyl, and propyl.
- 9. The compound of claim 7, wherein the acylated portion of the acylated basic radical has the formula: where R is C1-C8 alkyl, aryl, and C7-C12 substituted aryl; and X is a bond, C, O, or N.
- 10. The compound of claim 9, wherein the acylated portion is selected from the group consisting of
- 11. A compound selected from the group consisting of compounds represented by the following formulae or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof:
- 12. A compound selected from the group consisting of compounds represented by the following formulae or a pharmaceutically acceptable salt, solvate, or prodrug derivative thereof:
- 13. A platelet aggregation inhibiting pharmaceutically formulation comprising:(i) a therapeutically effective platelet aggregation inhibiting amount of a bicyclic compound of claim 1; and (ii) a pharmaceutically acceptable carrier or diluent therefor.
- 14. A method for effecting inhibition of platelet aggregation which comprises administering to a mammal in need thereof a therapeutically effective platelet aggregation inhibiting amount of the bicyclic compound of claim 1.
- 15. A method of inhibiting fibrinogen binding by contacting glycoprotein IIb-IIIa sites with the compound of claim 1.
- 16. A method of treating a mammal to alleviate the pathological effects of atherosclerosis and arteriosclerosis, acute myocardial infraction, chronic stable angina, unstable angina, transient ischemic attacks and strokes, peripheral vascular disease, arterial thrombosis, preeclampsia, embolism, restenosis following angioplasty, carotid endarterectomy, and anastomosis of vascular grafts; wherein the method comprises administering to said mammal at least one bicyclic compound of claim 1; wherein, said bicyclic compound is administered to said mammal in an amount sufficient to inhibit binding of fibrinogen on glycoprotein IIb-IIIa sites in said mammal to thereby inhibit said effects.
- 17. The method of claim 6, wherein said mammal is a human.
- 18. A bicyclic compound having a nucleus formed from two fused six-membered rings, A and B, represented by the formula (I), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof: the bicyclic nucleus of rings A and B is formula (17) below: R3 is an acidic group comprising a carboxylic acid radical selected from the following formulae: n is a number from 0 to 5; R0 is the same or different and is independently selected from the group consisting of hydrogen, alkyl, hydroxy, alkoxy, amino, substituted amino, halo, and ═O; linking group —(L)— is a divalent substituted or unsubstituted chain of from 1 to 2 atoms selected from the group consisting of carbon, nitrogen, and oxygen; and Q is a basic group selected from the group consisting of amidinophenyl, guanidinophenyl, and groups of the formula: wherein X is a halogen.
CROSS-REFERENCE TO RELATED APPLICATIONS
This application is a continuation of patent application Ser. No. 09/412,142, filed Oct. 5, 1999, now abandoned which is a continuation of Ser. No. 09/047,285, filed Mar. 24, 1998, now U.S. Pat. No. 6,020,362 which is a continuation of Ser. No. 08/376,191, filed Jan. 19, 1995, now U.S. Pat. No. 5,731,324, which is continuation-in-part of Ser. No. 08/255,821, filed Jul. 8, 1994, now U.S. Pat. No. 5,618,843, which is a continuation-in-part of Ser. No. 08/096,220, filed Jul. 22, 1993, abandoned.
US Referenced Citations (4)
Number |
Name |
Date |
Kind |
5039805 |
Alig et al. |
Aug 1991 |
A |
5041453 |
Huang et al. |
Aug 1991 |
A |
5059609 |
Eggler et al. |
Oct 1991 |
A |
5064814 |
Klein et al. |
Nov 1991 |
A |
Foreign Referenced Citations (18)
Number |
Date |
Country |
0 169 443 |
Jan 1986 |
EP |
0 315 399 |
Nov 1988 |
EP |
0 430 459 |
Nov 1990 |
EP |
0 435 235 |
Jul 1991 |
EP |
0 456 835 |
Nov 1991 |
EP |
0 531 883 |
Mar 1992 |
EP |
0 478 328 |
Apr 1992 |
EP |
0 540 051 |
May 1993 |
EP |
0 635 492 |
Jan 1995 |
EP |
0 655 439 |
May 1995 |
EP |
2 276 384 |
Sep 1994 |
GB |
WO 8904303 |
Jan 1989 |
WO |
WO 8904304 |
Jan 1989 |
WO |
WO 9220705 |
Nov 1992 |
WO |
WO 9300095 |
Jan 1993 |
WO |
WO 9308174 |
Apr 1993 |
WO |
WO 9312074 |
Jun 1993 |
WO |
WO 9429273 |
Dec 1994 |
WO |
Non-Patent Literature Citations (6)
Entry |
Chemical Abstracts; vol. 84. No. 13. Abstract 90500a dated Mar. 29, 1976, pp. 556; Barxzai-Beke, et al. |
Journal American Chemical Society; 1994 vol. 116. No. 116, pp. 5077-5083; McDowell, et al. |
Chemical Abstracts; vol. 75. No. 10. Abstract 7439ly dated Sep. 6, 1971, pp. 278; Satoh, et al. |
Journal American Chemical Society; 1993 vol. 115, pp. 8861-8862; Ku, et al. |
Annual Reports In Medicinal Chemistry; 1993 vol. 28, pp. 79-86; Blackburn, et al. |
Chemical Abstracts; vol. 100, No. 17. pp. 638, Abstract 138973n dated Apr. 23, 1984; Otsuka Pharmaceutical Co. |
Continuations (3)
|
Number |
Date |
Country |
Parent |
09/412142 |
Oct 1999 |
US |
Child |
09/883639 |
|
US |
Parent |
09/047285 |
Mar 1998 |
US |
Child |
09/412142 |
|
US |
Parent |
08/376191 |
Jan 1995 |
US |
Child |
09/047285 |
|
US |
Continuation in Parts (2)
|
Number |
Date |
Country |
Parent |
08/255821 |
Jul 1994 |
US |
Child |
08/376191 |
|
US |
Parent |
08/096220 |
Jul 1993 |
US |
Child |
08/255821 |
|
US |