Claims
- 1. A compound of formula I: wherein:A is a member selected from the group consisting of: where R6, R7, R8, and R9 are independently selected from the group consisting of H, —OH, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; m is an integer from 0-3; Z is a member selected from the group consisting of a direct link, C1-8alkyl, C3-8cycloalkyl, C2-8alkenyl, C2-8alkynyl, C1-8carbocyclic aryl, or a five to ten membered heterocyclic ring system containing 1-4 nitrogen atoms; n is an integer from 0-3; D is a member selected from the group consisting of a direct link, —O—, —NR2—, —C(═O)—, —S—, —SO2—, —SO2—NR2—, —NR2—SO2—, —OC(═O)—, —C(═O)O—, —C(═O)—NR2— and —NR2—C(═O)—; each R1 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, halogen, polyhaloalkyl, C0-8alkyl-C(═O)OH, C0-8alkyl-C(═O)O—C1-8alkyl, —CN, —NO2, C0-8alkyl-OH, C0-8alkyl-SH, —OR2 and —O—C(═O)R2, an unsubstituted amino group, a mono- or di-substituted amino group, wherein the substituted amino groups are independently substituted by at least one member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, polyhaloalkyl, C0-8alkyl-C(═O)OH and C0-8alkyl-C(═O)O—C1-8alkyl; R2 is selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; q is an integer from 0-3; R11 and R12 are each independently a member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, C6-12carbocyclic aryl, C1-6alkylaryl, C1-6alkyl-C3-8cycloalkyl, —OR2, —C(═O)—, —O—C(═O)R2, —C1-8alkyl-OR10, —C1-8alkyl-O—C(═O)R10, —C1-8alkyl-O—C(═O)OR10, —C1-8alkyl-C(═O)NR10R10, —C1-8alkyl-NR10R10, —C1-8alkyl-NR10C(═O)R10, —SR10, where R2 is as set forth above and each R10 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aryl and —C(═O)OR2 and wherein when two R10 groups are present they are optionally taken together to form a saturated or unsaturated ring with the atom to which they are both attached, or R11 and R12 are taken together to form an alkenyl double bond substituted by an R10 group, or R11 and R12 collectively form an oxygen atom having a double bond attachment to the ring carbon atom; p is an integer from 0-3; E is a direct link; J is a member selected from the group consisting of a direct link, a bivalent C3-8cycloalkyl group, phenylene and naphthalene; G is whereinR23, R24 and R25 are independently selected from the group consisting of H, —OH, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug compounds thereof.
- 2. A compound of claim 1 selected from the group consisting of:
- 3. A pharmaceutical composition for treating a condition in a mammal characterized by undesired thrombosis comprising a therapeutically acceptable carrier and a therapeutically effective amount of a compound of claim 1.
- 4. A method for treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of claim 1.
- 5. The method of claim 4 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.
- 6. A method for inhibiting the coagulation of a biological sample comprising the administration of a compound of claim 1.
- 7. A compound of claim 1, wherein:A is a member selected from the group consisting of: where R6, R7, R8, and R9 are independently selected from the group consisting of H, —OH, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; m is an integer from 0-3; Z is a five to ten membered heterocyclic ring system containing 1-4 nitrogen atoms; n is an integer from 0-3; D is a member selected from the group consisting of —O—, —NR2, —C(═O)—, —S— and —SO2—; each R1 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, halogen, polyhaloalkyl, C0-8alkyl-C(═O)OH, C0-8alkyl-C(═O)O—C1-8alkyl, —CN, —NO2, C0-8alkyl-OH, C0-8alkyl-SH, —OR2 and —O—C(═O)R2, an unsubstituted amino group, a mono- or di-substituted amino group, wherein the substituted amino groups are independently substituted by at least one member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, polyhaloalkyl, C0-8alkyl-C(═O)OH and C0-8alkyl-C(═O)O—C1-8alkyl; R2 is selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; q is an integer from 0-3; R11 and R12 are each independently a member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, C6-12carbocyclic aryl, C1-6alkylaryl, C1-6alkyl-C3-8cycloalkyl, —OR2, —C(═O)—, —O—C(═O)R2, —C1-8alkyl-OR10, —C1-8alkyl-O—C(═O)R10, —C1-8alkyl-O—C(═O)OR10, —C1-8alkyl-C(═O)NR10R10, —C1-8alkyl-NR10R10, —C1-8alkyl-NR10C(═O)R10, —SR10, where R2 is as set forth above and each R10 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aryl and —C(═O)OR2 and wherein when two R10 groups are present they are optionally taken together to form a saturated or unsaturated ring with the atom to which they are both attached, or R11 and R12 are taken together to form an alkenyl double bond substituted by an R10 group, or R11 and R12 collectively form an oxygen atom having a double bond attachment to the ring carbon atom; p is an integer from 0-3; E is a direct link;. J is a member selected from the group consisting of phenylene and naphthalene; G is whereinR23, R24 and R25 are independently selected from the group consisting of H, —OH, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug compounds thereof.
- 8. A compound of claim 1, wherein:A is a member selected from the group consisting of: where R6, R7, R8, and R9 are independently selected from the group consisting of H, —OH, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; m is an integer from 0-3; Z is piperidinyl; n is an integer from 0-3; D is —O—; each R1 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, halogen, polyhaloalkyl, C0-8alkyl-C(═O)OH, C0-8alkyl-C(═O)O—C1-8alkyl, —CN, —NO2, C0-8alkyl-OH, C0-8alkyl-SH, —OR2 and —O—C(═O)R2, an unsubstituted amino group, a mono- or di-substituted amino group, wherein the substituted amino groups are independently substituted by at least one member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, polyhaloalkyl, C0-8alkyl-C(═O)OH and C0-8alkyl-C(═O)O—C1-8alkyl; R2 is selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; q is an integer from 0-3; R11 and R12 are each independently a member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl, C6-12carbocyclic aryl, C1-6alkylaryl, —C1-6alkyl-C3-8cycloalkyl, —OR2, —C(═O)—, —O—C(═O)R2, —C1-8alkyl-OR10, —C1-8alkyl-O—C(═O)R10, —C1-8alkyl-O—C(═O)OR10, —C1-8alkyl-C(═O)NR10OR10, —C1-8alkyl-NR10R10, —C1-8alkyl-NR10C(═O)R10, —SR10, where R2 is as set forth above and each R10 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aryl and —C(═O)OR2 and wherein when two R10 groups are present they are optionally taken together to form a saturated or unsaturated ring with the atom to which they are both attached, or R11 and R12 are taken together to form an alkenyl double bond substituted by an R10 group, or R11 and R12 collectively form an oxygen atom having a double bond attachment to the ring carbon atom; p is an integer from 0-3; E is a direct link; J is naphthalene; G is whereinR23, R24 and R25 are independently selected from the group consisting of H, —OH, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, C3-8cycloalkyl and C6-12carbocyclic aryl; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug compounds thereof.
- 9. A compound of claim 1, wherein:A is a member selected from the group consisting of: where R6, R7, R8, and R9 are independently selected from the group consisting of H and C1-8alkyl; m is an integer from 0-3; Z is piperidinyl; n is an integer from 0-3; D is —O—; each R1 is a member independently selected from the group consisting of H, halogen, polyhaloalkyl, C0-8alkyl-C(═O)OH, C0-8alkyl-C(═O)O—C1-8alkyl, C0-8alkyl-OH, —OR2 and —O—C(═O)R2, an unsubstituted amino group, a mono- or di-substituted amino group, wherein the substituted amino groups are independently substituted by at least one member selected from the group consisting of H, C0-8alkyl-C(═O)OH and C0-8alkyl-C(═O)O—C1-8alkyl; R2 is selected from the group consisting of H and C1-8alkyl; q is an integer from 0-3; R11 and R12 are each independently a member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, —C(═O)—, or R11 and R12 are taken together to form an alkenyl double bond substituted by an R10 group, where each R10 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aryl and —C(═O)OR2, or R11 and R12 collectively form an oxygen atom having a double bond attachment to the ring carbon atom; p is an integer from 0-3; E is a direct link; J is naphthalene; G is whereinR23, R24 and R25 are independently selected from the group consisting of H and C1-8alkyl; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug compounds thereof.
- 10. A compound of claim 1, having the following structural formula: whereinA is a member selected from the group consisting of: each R1 is a member independently selected from the group consisting of H, halogen, polyhaloalkyl, C0-8alkyl-C(═O)OH, C0-8alkyl-C(═O)O—C1-8alkyl, C0-8alkyl-OH, —OR2 and —O—C(═O)R2, an unsubstituted amino group, a mono- or di-substituted anmio group, wherein the substituted amino groups are independently substituted by at least one member selected from the group consisting of H, C0-8alkyl-C(═O)OH and C0-8alkyl-C(═O)O—C1-8alkyl; R2 is selected from the group consisting of H and C1-8alkyl; q is an integer from 0-3; R11 and R12 are each independently a member selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, —C(═O)—, or R11 and R12 are taken together to form an alkenyl double bond substituted by an R10 group, where each R10 is a member independently selected from the group consisting of H, C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aryl and —C(═O)OR2, or R11 and R12 collectively form an oxygen atom having a double bond attachment to the ring carbon atom; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug compounds thereof.
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims benefit of priority under 35 U.S.C. §119(e) to U.S. Provisional Application No. 60/191,720 filed on Mar. 24, 2000, which is incorporated here in its entirety by reference.
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