IP Library Granted Patent US 7,022,731
Granted Patent B2
US 7,022,731 · App. 10/759,396 · Granted Apr 4, 2006

Platelet ADP receptor inhibitors

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 7,022,731
App. No.
10/759,396
Granted
Apr 4, 2006
Kind
B2
Abstract

Novel compounds of formula (I) to (VI), which more particularly include sulfonylurea derivatives, sulfonylthiourea derivatives, sulfonylguanidine derivatives, sulfonylcyanoguanidine derivatives, thioacylsulfonamide derivatives, and acylsulfonamide derivatives which are effective platelet ADP receptor inhibitors. These derivatives may be used in various pharmaceutical compositions, and are particularly effective for the prevention and/or treatment of cardiovascular diseases, particularly those diseases related to thrombosis. The invention also relates to a method for preventing or treating thrombosis in a mammal comprising the step of administering a therapeutically effective amount of a compound of formulae (I)–(VI), or a pharmaceutically acceptable salt thereof.

Claims (36)

1. A compound selected from the group consisting of formula (I) and formula (II):

wherein

A is thienyl optionally substituted with one, two or three substituents independently selected from the group consisting of lower alkoxy, lower alkyl, loweralkylamino, hydroxy, halogen, cyano, hydroxyl, mercapto, nitro, thioalkoxy, carboxaldehyde, carboxyl, carboalkoxy and carboxamide;

W is 1,4-phenylene optionally substituted with one, two or three substituents independently selected from the group consisting of lower alkoxy, lower alkyl, lower alkylamino, hydroxy, halogen, cyano, hydroxyl, mercapto, nitro, thioalkoxy, carboxaldehyde, carboxyl, carboalkoxy and carboxamide;

E is selected from the group consisting of H, —C 1 –C 8 alkyl, polyhaloalkyl, —C 3-8 -cycloalkyl, aryl optionally substituted with one, two or three substituents independently selected from the group consisting of lower alkoxy, lower alkyl, lower alkylamino, hydroxy, halogen, cyano, hydroxyl, mercapto, nitro, thioalkoxy, carboxaldehyde, carboxyl, carboalkoxy and carboxamide;

D is

wherein:

n is an integer from 0–4,

X is in each case a member independently selected from the group consisting of:

halogen, polyhaloalkyl, —OR 3 , —SR 3 , —CN, —NO 2 , —SO 2 R 3 —C 1-10 -alkyl, —C 3-8 -cycloalkyl, aryl, aryl-substituted by 1–4 R 3 groups, amino, amino-C 1-8 -alkyl, C 1-3 -acylamino, C 1-3 -acylamino-C 1-8 -alkyl, C 1-6 -alkylamino, C 1-6 -alkylamino C 1-8 alkyl, C 1-6 dialkylamino, C 1-6 dialkylamino C 1-8 alkyl, C 1-6 alkoxy, C 1-6 alkoxy-C 1-6 -alkyl, carboxy-C 1-6 -alkyl, C 1-3 -alkoxycarbonyl, C 1-3 -alkoxycarbonyl-C 1-6 -alkyl, carboxy C 1-6 alkyloxy, hydroxy, hydroxy C 1-6 alkyl, and a 5 to 10 membered fused or non-fused aromatic or nonaromatic heterocyclic ring system, having 1 to 4 heteroatoms independently selected from N, O, and S, with the proviso that the carbon and nitrogen atoms, when present in the heterocyclic ring system, are unsubstituted, mono- or di-substituted independently with 0–2 R 4 groups,

wherein R 3 and R 4 are each independently selected from the group consisting of:

hydrogen, halogen, —CN, —NO 2 , —C 1-10 alkyl, C 3-8 -cycloalkyl, aryl, amino, amino-C 1-8 -alkyl, C 1-3 -acylamino, C 1-3 -acylamino-C 1-8 -alkyl, C 1-6 -alkylamino, C 1-6 -alkylamino C 1-8 alkyl, C 1-6 dialkylamino, C 1-6 dialkylannino C 1-8 alkyl, C 1-6 alkoxy, C 1-6 alkoxy —C 1-6 -alkyl, carboxy-C 1-6 -alkyl, C 1-3 -alkoxycarbonyl, C 1-3 -alkoxycarbonyl-C 1-6 -alkyl, carboxy-C 1-6 -alkyloxy, hydroxy, hydroxy-C 1-6 -alkyl, -thio and thio-C 1-6 -alkyl;

Y is selected from the group consisting of O, S, N—OR 5 , and NR 5 ,

wherein R 5 is selected from the group consisting of:

H, C 1-10 alkyl, C 3-8 -cycloalkyl, and CN;

or pharmaceutically acceptable salts thereof.

2. A pharmaceutical composition comprising a therapeutically effective amount of a compound according to claim 1 , or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

3. A method for preventing or treating thrombosis in a mammal comprising the step of administering to a mammal a therapeutically effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

4. A method of claim 3 , wherein said mammal is a human.

5. A method of claim 3 , wherein said mammal is prone to or suffers from a cardiovascular disease selected from at least one of the group consisting of acute myocardial infarction, unstable angina, chronic stable angina, transient ischemic attacks, strokes, peripheral vascular disease, preeclampsia/eclampsia, deep venous thrombosis, embolism, disseminated intravascular coagulation and thrombotic cytopenic purpura, thrombotic and restenotic complications following invasive procedures resulting from angioplasty, carotid endarterectomy, post CABG (coronary artery bypass graft) surgery, vascular gram surgery, stent placements and insertion of endovascular devices and protheses.

6. A compound of claim 1 having the following formula:

wherein:

n is an integer from 0–4;

X is selected from the group consisting of 3-Br, 3-Cl, 4-OMe, 3-SOMe, 3-N(Me) 2 , and 3,4-dimethyl;

W is selected from the group consisting of:

Y is selected from the group consisting of: O, S, N—C≡N, NH and N—OH; and

A is selected from the group consisting of:

7. A compound of claim 1 , having the following formula:

wherein:

Y is selected from the group consisting of: O, N—C≡N, NH and N—OH; and

A is selected from the group consisting of:

8. A compound of claim 1 , wherein A is thienyl.

9. A compound of claim 1 , wherein Y is O.

10. A compound of claim 1 , wherein E is hydrogen.

11. A compound of claim 1 , selected from the group consisting of

12. A compound of claim 1 , having the formula:

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 12, 2021
From: PORTOLA PHARMACEUTICALS, LLC
To: ALEXION PHARMACEUTICALS, INC.
Reel/Frame 054975/0203 →
CHANGE OF NAME Recorded Jan 12, 2021
From: PORTOLA PHARMACEUTICALS, INC.
To: PORTOLA PHARMACEUTICALS, LLC
Reel/Frame 054976/0294 →