Claims
- 1. A compound represented by the formula:
- 2. A compound according to claim 1, wherein:
A is a member selected from the group consisting of: R2, —NR3R4, 132wherein R2, R3, R4, R5, R6, R7, R8, and R9 are independently selected from the group consisting of H, —OH, C1-6alkyl, C3-8cycloalkyl, aryl, a five to ten membered heterocyclic ring system containing 1-4 heteroatoms selected from the group consisting of N, O and S, and C1-4alkylheterocyclic ring system having in the ring system 5 to 10 atoms with 1 to 4 of such atoms being selected from the group consisting of N, O and S; where R6 taken with either of R7 and R8, and/or R7 taken with R8, can each form a 5 to 6 membered heterocyclic ring containing from 1 to 4 atoms selected from the group consisting of N, O and S; m is an integer from 0-2; Z is a member selected from the group consisting of a direct link, C1-6alkyl, C3-8cycloalkyl, C1-6alkenyl, aryl, or a five to ten membered heterocyclic ring system containing 1-4 heteroatoms selected from the group consisting of N, O and S; n is an integer from 0-2; D is a member selected from the group consisting of a direct link, —O—, —NR11, —C(═O)—, —S—, —SO2—, —SO2—NR2, —NR2—SO2, —OCO—, —C(═O)NR2, and —NR2—C(═O) —; R1 is a member selected from the group consisting of H, C1-6alkyl, halogen, a —C(═O)OH group, an unsubstituted amino group, a mono- or di-substituted amino group, —CN, —NO2, —OH, —O—R2 and —O—C(═O)R2, where R2 is as set forth above; q is an integer from 0-2; X is —NR12— or —CHR 12—; R11 and R12 are independently a member selected from the group consisting of H, C1-6alkyl, C3-8cycloalkyl, aryl, C1-4alkylaryl, C1-4alkyl—C3-8cycloalkyl, —O—R2, —O—C(═O)R2, —C1-6alkyl—O—R10, —C1-6alkyl—O—C(═O)R10, —C1-6alkyl—O—C(═O)OR10, —C1-6alkyl—C(═O)NR10OR10, —C1-6alkyl-NR10R10, —C1-6alkyl—NR10OC(═O)R10, —SR10, where R2 is as set forth above and R10 is a member selected from the group consisting of H, C1-6alkyl, and wherein when two R10 groups are present they may be taken together to form a saturated or unsaturated ring with the atom to which they are both attached; p is an integer from 0-2; E is a member selected from the group consisting of a direct link, —O—, —NR11, —(CH2)0-3—C(═O)—NH—(CH2)0-3—, —CH(CO2R11)(CH2)0-3—, —CH(CONR11)(CH2)0-3—, where R11 is as described above, phenylene, a 5 to 12 membered heteroaryl group containing 1 to 4 heteroatoms selected from the group consisting of N, O and S, and a five to ten membered non-aromatic heterocyclic ring system containing 1-4 heteroatoms selected from the group consisting of N, O and S, wherein said heteroaryl and said non-aromatic heterocyclic ring structure may be independently substituted by from 0 to 5 R14 groups; each R14 group is independently a member selected from the group consisting of H, C1-6alkyl, halogen, a —C(═O)OH group, an unsubstituted amino group, a mono- or di-substituted amino group, —CN, —NO2, —OH, —O—R2 and —O—C(═O)R2, where R2 is as set forth above; J is a member selected from the group consisting of a direct link, C3-8cycloalkyl, phenylene, naphthalene, a 5 to 12 membered heteroaryl group containing 1 to 4 heteroatoms selected from the group consisting of N, O and S, and a five to ten membered non-aromatic heterocyclic ring system containing 1-4 heteroatoms selected from the group consisting of N, O and S wherein said heteroaryl and said non-aromatic heterocyclic ring structure may be independently substituted by from 0 to 5 R14 groups, where R14 is as set forth above; G is a member selected from the group consisting of: H, —CN, —OR17, 133wherein t is an integer from 0 to 6; u is the integer 0 or 1; and R17, R18, R19, R20, R21, R22, R23, R24, R25 and R26 are independently selected from the group consisting of H, —OH, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, C6-12carbocyclic aryl, a five to ten membered heterocyclic ring system containing 1-4 heteroatoms selected from the group consisting of N, O and S, and C1-6alkylheterocyclic ring system having in the ring system 5 to 10 atoms with 1 to 4 of such atoms being selected from the group consisting of N, O and S; where R18 taken with R19, R22 taken with either of R24 and R25, and R24 taken with R25, can each independently form a 5 to 6 membered heterocyclic ring containing from 1 to 4 atoms selected from the group consisting of N, O and S; with the proviso that when G is H, —CN, or —OR17, either E or J must contain at least one N atom; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof.
- 3. A compound according to formula II:
- 4. A compound according to claim 3, wherein:
m is an integer from 0-2; n is an integer from 0-2; D is a member selected from the group consisting of —O—, —NR2, —C(═O)—, —S—, and —SO2—; q is an integer from 0-2; and p is an integer from 0-2.
- 5. A compound according to claim 3 having the following structural formula IV:
- 6. A compound according claim 5, wherein:
R1, R8, R11 and R14 groups are independently selected from the group consisting of hydrogen, methyl and ethyl.
- 7. A compound according to 5, wherein:
A is a member selected from the group consisting of: 140CH3—H—, NH2—, (CH3—)2NCO—, 141Z is a member selected from the group consisting of: 142n is an integer from 0-2; D is a member selected from the group consisting of: —O—, —N(CH3)—, and —CH2—; q is 0; and G is 143
- 8. A compound according to claim 5 having the following structural formula:
- 9. A compound according to formula III:
- 10. A compound according to claim 9, wherein:
R1 and R8 are each independently a lower alkyl group; and R11 is hydrogen or a C1-C8 alkyl group.
- 11. A compound according to claim 9, wherein:
R1 and R11 are each independently hydrogen or a C1-C6 alkyl group; R8 is a methyl group; p is an integer from 1-2; E is a member selected from the group consisting of:
direct link 147J is a member selected from the group consisting of: 148G is a member selected from the group consisting of: 149—NH2, 150and —CH3.
- 12. A compound of claim 1 having the following structural formula:
- 13. A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of one of the claims 1-12.
- 14. A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of one of the claims 1-12.
- 15. The method of claim 14, wherein the condition is selected from the group consisting of:
acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation such as cardiac or other intravascular catheterization, intra-aortic balloon pump, coronary stent or cardiac valve, and conditions requiring the fitting of prosthetic devices.
- 16. A method for inhibiting the coagulation of a biological sample comprising the administration of a compound of one of the claims 1-12.
CROSSED REFERENCE TO RELATED APPLICATIONS
[0001] This application claims benefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional application Ser. No. 60/192,619 filed on Mar. 24, 2000, which is incorporated here in its entirety by reference.
Provisional Applications (1)
|
Number |
Date |
Country |
|
60192619 |
Mar 2000 |
US |