Alpha-IIb-beta-3 inhibitors and uses thereof

1. A method for inhibiting or reducing platelet aggregation and/or adhesion comprising administering to a subject in need thereof an effective amount of a compound of formula I-C:

wherein:

i) A is S, N, C or O;

ii) X is a single bond-or optionally substituted and saturated or unsaturated C 1 -C 4 alkylene, C 3 -C 10 cycloalkylene optionally containing one or more heteroatoms selected from a group consisting of O or N, —N(R 6 )— or —C 1 -C 4 alkyl-N(R 6 )—;

iii) Y is a single bond or optionally substituted and saturated or unsaturated C 1 -C 4 alkylene, optionally substituted -aryl-, -arylalkylene-, -heteroaryl-, —C(O)—, —N(R 6 )C(O)—, —R 3 C(O)—, —R 3 -alkylamido- or —R 3 —NHC(O)—;

iv) R 1 is C 1 -C 4 alkyl;

v) R 3 is H or optionally substituted and saturated or unsaturated C 1 -C 4 alkyl, optionally substituted (R 6 )N—, —(R 4 )(R 5 )N—, —N(R 4 )(R 5 )—C 1 -C 4 alkyl-, aryl, heteroaryl, arylC 1 -C 4 alkyl, heteroarylC 1 -C 4 alkyl, or C 3 -C 8 cycloalkyl optionally containing one or more heteroatoms selected from a group consisting of O or N;

vi) R 4 and R 5 are linked together via a covalent bond so as to form a C 3 -C 8 cycloalkylene containing a nitrogen atom;

vii) R 6 is H, C 1 -C 4 alkyl, aryl or arylC 1 -C 4 alkyl,

in free or pharmaceutically acceptable salt form;

such that platelet aggregation and/or adhesion is reduced.

2. A method for the treatment or prophylaxis of a thrombotic disorder selected from a group consisting of stroke, myocardial infarction, unstable angina, abrupt closure following angioplasty or stent placement, thrombosis induced by peripheral vascular surgery, peripheral vascular disease and thrombotic disorders resulting from atrial fibrillation or inflammation, comprising administering to a subject in need thereof an effective amount of a Compound of Formula I-C:

wherein:

i) A is S, N, C or O;

ii) X is a single bond or optionally substituted and saturated or unsaturated C 1 -C 4 alkylene, C 3 -C 10 cycloalkylene optionally containing one or more heteroatoms selected from a group consisting of O or N, —N(R 6 )— or —C 1 -C 4 alkyl-N(R 6 )—;

iii) Y is a single bond or optionally substituted and saturated or unsaturated C 1 -C 4 alkylene, optionally substituted -aryl-, -arylalkylene-, -heteroaryl-, —C(O)—, —N(R 6 )C(O)—, —R 3 C(O)—, —R 3 -alkylamido- or —R 3 —NHC(O)—;

iv) R 1 is C 1 -C 4 alkyl;

v) R 3 is H or optionally substituted and saturated or unsaturated C 1 -C 4 alkyl, optionally substituted (R 6 )N—, —(R 4 )(R 5 )N—, —N(R 4 )(R 5 )—C 1 -C 4 alkyl-, aryl, heteroaryl, arylC 1 -C 4 alkyl, heteroarylC 1 -C 4 alkyl, or C 3 -C 8 cycloalkyl optionally containing one or more heteroatoms selected from a group consisting of O or N;

vi) R 4 and R 5 are linked together via a covalent bond so as to form a C 3 -C 8 cycloalkylene containing a nitrogen atom;

vii) R 6 is H, C 1 -C 4 alkyl, aryl or arylC 1 -C 4 alkyl, in free or pharmaceutically acceptable salt form.

3. The method according to claim 1 , wherein said Compound is 2-ethyl-7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one in free or pharmaceutically acceptable salt form.

4. The method according to claim 2 , further comprises administering an effective amount of at least one therapeutic agent selected from a group consisting of anti-coagulant, antiplatelet, and fibrinolytic agents in conjunction with the compound as described in claim 2 .

5. The method according to claim 4 , wherein said therapeutic agent is selected from a group consisting of heparin, low molecular weight heparins, bivalirudin, Fondaparinux, warfarin, Acenocoumarol, Phenprocoumon, Phenindione, Abbokinase (urokinase), streptokinase, alteplase, retaplase, tenecteplase, prasugrel, aspirin, ticlopidine, clopidogrel, abciximab, eptifibatide and tirofiban.

6. The method according to claim 5 wherein said therapeutic agent is heparin.

7. The method according to claim 2 , wherein said Compound is 2-ethyl-7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one in free or salt form.

8. The method according to claim 2 , wherein R 3 is selected from a group consisting of cyclopentyl, cyclohexyl, piperazinyl, methylpiperazinyl, ethylpiperazinyl, propylpiperazinyl, piperidinyl, azepanyl, pyrrolidinyl, imidazolidinyl, methylpyrrolidinyl, ethylpyrrolidinyl, morpholinyl and tetrahydroquinolinyl, in free or pharmaceutically acceptable salt form.

9. The method according to claim 2 , wherein R 4 and R 5 are linked together via a covalent bond so as to form a piperidinylene, in free or pharmaceutically acceptable salt form.

10. The method according to claim 2 , wherein A is S; X is a single bond; and Y is a single bond; in free or pharmaceutically acceptable salt form.

11. The method according to claim 7 , further comprises administering an effective amount of at least one therapeutic agent selected from a group consisting of anti-coagulant, antiplatelet, and fibrinolytic agents in conjunction with the compound as described in claim 7 .

12. The method according to claim 7 , further comprises administering an effective amount of at least one therapeutic agent selected from a group consisting of heparin, low molecular weight heparins, bivalirudin, fondaparinux, warfarin, acenocoumarol, phenprocoumon, phenindione, urokinase, streptokinase, alteplase, retaplase, tenecteplase, prasugrel, aspirin, ticlopidine, clopidogrel, abciximab, eptifibatide and tirofiban.

13. The method according to claim 11 wherein said therapeutic agent is heparin.

14. The method according to claim 10 , further comprises administering an effective amount of at least one therapeutic agent selected from a group consisting of anti-coagulant, antiplatelet, and fibrinolytic agents in conjunction with the compound as described in claim 10 .

15. The method according to claim 10 , further comprises administering an effective amount of at least one therapeutic agent selected from a group consisting of heparin, low molecular weight heparins, bivalirudin, fondaparinux, warfarin, acenocoumarol, phenprocoumon, phenindione, urokinase, streptokinase, alteplase, retaplase, tenecteplase, prasugrel, aspirin, ticlopidine, clopidogrel, abciximab, eptifibatide and tirofiban.

16. The method according to claim 15 , wherein said therapeutic agent is heparin

17. the method according to claim 1 , wherein A is S; X is a single bond; and Y is a single bond; in free or pharmaceutically acceptable salt form.