US5618843A
Expired / Lapsed
US
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Glycoprotein IIb/IIIa antagonists
Assignee: Eli Lilly and Co
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Filing: 1994-07-08
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Granted: 1997-04-08
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Expires: 2014-07-08
Abstract
Abstract This invention relates to certain bicyclic compounds having a nucleus formed of two fused six membered rings, for example, isoquinoline, isoquinolone, tetrahydronaphthalene, dihydronaphthalene, or tetralone, substituted with both basic and acidic functionality, which are useful in inhibition of platelet aggregation.
Inventors
- 👤 Matthew J. Fisher
- 👤 Anne M. Happ
- 👤 Joseph A. Jakubowski
- 👤 Michael D. Kinnick
- 👤 Allen D. Kline
- 👤 John M. Morin, Jr.
- 👤 Daniel J. Sall
- 👤 Marshall A. Skelton
- 👤 Robert T. Vasileff
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 17:35
CPC Classifications
C; C07; C07D; C07D241/00; C07D241/36; C07C; C07C271/00; C07C271/62; C07C271/64; A; A61; A61P; A61P3/00; A61P3/06; A61P43/00; A61P7/00; A61P7/02; A61P9/00; A61P9/10; C07C257/00; C07C257/10; C07C257/18; C07D211/00; C07D211/04; C07D211/06; C07D211/08; C07D211/18; C07D211/20; C07D211/22; C07D211/34; C07D213/00; C07D213/02; C07D213/04; C07D213/60; C07D213/78; C07D213/81; C07D213/82; C07D217/00; C07D217/02; C07D217/04; C07D217/06; C07D217/22; C07D217/24; C07D311/00; C07D311/02; C07D311/04; C07D311/22; C07D311/58; C07D333/00; C07D333/02; C07D333/04; C07D333/26; C07D333/38; C07D401/00; C07D401/02; C07D401/12; C07D405/00; C07D405/02; C07D405/06; C07D405/12; C07C2602/00; C07C2602/02; C07C2602/04; C07C2602/10
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
18 words
A compound selected from the group represented by formulae XXXV1a and XLVIIIa shown below: ##STR99## or mixtures thereof.
Claim 2
Dependent Claim
18 words
A compound selected from the group represented by formulae XXXV1a and XLVIIIa shown below: ##STR99## or mixtures thereof.
Claim 3
Dependent Claim
223 words
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: ##STR100## wherein the bicyclic nucleus of rings A and B is selected from the group consisting of formulae (a), (c), (e), and (q) as follows: ##STR101## R 3 is an acidic group selected from, ##STR102## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR103## and Q is an organic group represented by the formula, ##STR104## R 20 is the same or different and is independently selected from hydrogen, alky, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer form 0 to 8.
Claim 4
Dependent Claim
223 words
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: ##STR100## wherein the bicyclic nucleus of rings A and B is selected from the group consisting of formulae (a), (c), (e), and (q) as follows: ##STR101## R 3 is an acidic group selected from, ##STR102## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR103## and Q is an organic group represented by the formula, ##STR104## R 20 is the same or different and is independently selected from hydrogen, alky, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer form 0 to 8.
Claim 5
Dependent Claim
30 words
A method for effecting inhibition of platelet aggregation which comprises administering to a mammal in need thereof an effective platelet aggregation inhibiting amount of the bicyclic compound of claim 2.
Claim 6
Dependent Claim
17 words
A method of inhibiting fibrinogen binding by contacting glycoprotein IIb-IIIa sites with the compound of claim 2.
Claim 7
Dependent Claim
91 words
A method of treating a human to alleviate the pathological effects of atherosclerosis and arteriosclerosis, acute myocardial infarction, 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 human at least one bicyclic compound of claim 2; wherein, said bicyclic compound is administered to said human in an amount sufficient to inhibit binding of fibrinogen on glycoprotein IIb-IIIa sites in said human to thereby inhibit said effects.
Claim 8
Dependent Claim
186 words
A bicyclic tetralin compound having a nucleus formed from two fused six membered rings, represented by the formula (IV), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof: ##STR105## wherein; R 3 is an acidic group selected from, ##STR106## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR107## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 9
Dependent Claim
186 words
A bicyclic tetralin compound having a nucleus formed from two fused six membered rings, represented by the formula (IV), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof: ##STR105## wherein; R 3 is an acidic group selected from, ##STR106## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR107## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 10
Dependent Claim
13 words
The compound of claim 6 where R 3 comprises a carboxyl acid radical.
Claim 11
Dependent Claim
186 words
A bicyclic tetralone compound having a nucleus formed from two fused six membered rings, represented by the formula (V), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof; ##STR108## wherein; R 3 is an acidic group selected from, ##STR109## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR110## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 12
Dependent Claim
186 words
A bicyclic tetralone compound having a nucleus formed from two fused six membered rings, represented by the formula (V), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof; ##STR108## wherein; R 3 is an acidic group selected from, ##STR109## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR110## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 13
Dependent Claim
13 words
The compound of claim 8 where R 3 comprises a carboxyl acid radical.
Claim 14
Dependent Claim
186 words
A bicyclic dihydronaphthlene compound having a nucleus formed from two fused six membered rings, represented by the formula (VI), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof; ##STR111## wherein; R 3 is an acidic group selected from, ##STR112## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR113## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 15
Dependent Claim
186 words
A bicyclic dihydronaphthlene compound having a nucleus formed from two fused six membered rings, represented by the formula (VI), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof; ##STR111## wherein; R 3 is an acidic group selected from, ##STR112## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR113## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 16
Dependent Claim
13 words
The compound of claim 10 where R 3 comprises a carboxyl acid radical.
Claim 17
Dependent Claim
178 words
A bicyclic naphthalene compound having a nucleus formed from two fused six membered rings, represented by the formula (VII), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof; ##STR114## wherein; ##STR115## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR116## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 18
Dependent Claim
178 words
A bicyclic naphthalene compound having a nucleus formed from two fused six membered rings, represented by the formula (VII), or a pharmaceutically acceptable salt, solvate or prodrug derivative thereof; ##STR114## wherein; ##STR115## n is a number from 2 to 6; R 0 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; m is a number from 2 to 6; R 10 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, aralkoxy, carboxy, acyl, cyano, halo, nitro, sulfo, ═O, and ═S; linking group -(L)- is a linking group is selected from groups represented by the formulae; ##STR116## R 20 is the same or different and is independently selected from hydrogen, alkyl, halosubstituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, hydroxy, alkoxy, arylalkoxy, amino, substituted amino, carbamyl, carboxy, acyl, cyano, halo, nitro, and sulfo; and p is an integer from 0 to 8.
Claim 19
Dependent Claim
13 words
The compound of claim 12 where R 3 comprises a carboxyl acid radical.
Claim 20
Dependent Claim
40 words
A compound selected from the group consisting of compounds represented by the following formulae XXXII, XXXIII, XXXIV, XXXV, XXXVII, XXXVIII, XL, XLI, XLIII, XLIV, XLV, XLVI, XLVIII, and XLIX; and all pharmaceutically acceptable salts, solyates and prodrug derivatives thereof: ##STR117##
Claim 21
Dependent Claim
40 words
A compound selected from the group consisting of compounds represented by the following formulae XXXII, XXXIII, XXXIV, XXXV, XXXVII, XXXVIII, XL, XLI, XLIII, XLIV, XLV, XLVI, XLVIII, and XLIX; and all pharmaceutically acceptable salts, solyates and prodrug derivatives thereof: ##STR117##
Claim 22
Dependent Claim
30 words
A compound selected from the group consisting of compounds represented by the following formulae LIV, LV, LXI, and LXII; and all pharmaceutically acceptable salts, solyates and prodrug derivatives thereof: ##STR118##
Claim 23
Dependent Claim
30 words
A compound selected from the group consisting of compounds represented by the following formulae LIV, LV, LXI, and LXII; and all pharmaceutically acceptable salts, solyates and prodrug derivatives thereof: ##STR118##
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 2000-04-07 | 2000-10-07 | 2001-04-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2004-04-07 | 2004-10-07 | 2005-04-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2008-04-07 | 2008-10-07 | 2009-04-08 | $7700.00 | Window Closed / Lapsed |