N-LINKED ARYL HETEROARYL INHIBITORS OF LTA4H FOR TREATING INFLAMMATION

Abstract

The present invention relates to a chemical genus of biaryl nitrogen-attached heterocycles that are inhibitors of LTA4H (leukotriene A4 hydrolase). The compounds have the general formula:

Description

Claims

1. A compound of formula:

2. A compound according to claim 1, wherein Q is —O—.

3. A compound according to claim 2, wherein ring (a) is chosen from an indazole, an indole and an isoindole ring.

4. A compound according to claim 3 of formula:

5. A compound according to claim 2, wherein HET is chosen from piperidine and pyrrolidine;Z is (CH2)0-10; in which one or two (CH2) may optionally be replaced by —O—, —NR10—, —SO—, —S(O)2—, —C(═O)— or —C═O(NH), andW is selected from the group consisting of hydrogen, acyl, hydroxy, carboxy, amino, carboxamido and aminoacyl.

6. A compound according to claim 5 of formula

7. A compound according to claim 5 of formula

8. A compound according to claim 3 of formula:

9. A compound according to claim 8, wherein HET is chosen from piperidine and pyrrolidine;Z is (CH2)0-10; in which one or two (CH2) may optionally be replaced by —O—, —NR10—, —SO—, —S(O)2—, —C(═O)— or —C═O(NH), andW is selected from the group consisting of hydrogen, acyl, hydroxyl, carboxyl, amino, carboxamido and aminoacyl.

10. A compound according to claim 3 of formula:

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of at least one compound according to claim 1.

12. A method for inhibiting leukotriene A4 hydrolase comprising contacting the LTA4H enzyme with a therapeutically effective amount of a compound according to claim 1.

13. A method for treating a disorder associated with leukotriene A4 hydrolase comprising administering to a mammal a therapeutically effective amount of a compound or a salt, hydrate or ester thereof according to claim 1.

14. A method according to claim 13 wherein said disorder is associated with inflammation.

15. A method according to claim 14 wherein said disorder is selected from allergic inflammation, acute inflammation and chronic inflammation.

16. A method according to claim 13 wherein said disorder is chosen from asthma, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, multiple sclerosis, inflammatory bowel diseases (IBD) and psoriasis.

17. A method according to claim 13 wherein said disorder is chosen from atherosclerosis, thrombosis, stroke, acute coronary syndrome, stable angina, peripheral vascular disease, critical leg ischemia, intermittent claudication, abdominal aortic aneurysm and myocardial infarction.