Carbamate Stereoisomer
The compound of formula (I) is a water-stable, long acting β 2 -selective adrenoceptor agonist useful as a bronchodilator in the treatment of bronchoconstriction associated with reversible obstructive airways diseases and the like.
1. A compound of formula (I)
or a pharmaceutically acceptable salt thereof.
2. A mixture of isomers of methyl [2-hydroxy-5-[1-hydroxy-2-[[(2-(4-hydroxyphenyl)-1-methylethyl]amino]ethyl]-phenyl] carbamate, wherein the mixture comprises at least 90% by weight of the isomer
3. A compound as claimed in claim 1 , which is in the form of a D-tartrate salt.
4. A compound as claimed in claim 2 , which is in the form of a D-tartrate salt.
5. A compound of general formula (IV)
or a salt thereof, in which P 1 and P 2 each represents a hydrogen atom or a hydroxyl protecting group, and P 3 represents a hydrogen atom or a benzylic amine protecting group, provided that at least one of P 1 , P 2 and P 3 represents a protecting group.
6. A pharmaceutical composition, which comprises a compound as claimed in any one of claims 1 to 3 or 4 and a pharmaceutically acceptable carrier.
7. A pharmaceutical composition as claimed in claim 6 , which further comprises a steroid.
8. A pharmaceutical composition as claimed in claim 7 , in which the steroid is beclomethasone, triamcinolone, funisolide, mometasone, budesonide or fluticasone.
9. A pharmaceutical composition as claimed in claim 6 , which further comprises a muscarinic receptor antagonist.
10. A pharmaceutical composition as claimed in claim 9 , in which the muscarinic receptor antagonist is ipratropium or tiatropium.
11. A pharmaceutical composition as claimed in claim 6 which further comprises an anticholinergic.
12. A pharmaceutical composition as claimed in claim 11 , in which the anticholinergic is glycopyrrolate.
13. A pharmaceutical composition as claimed in claim 6 which further comprises a mucolytic.
14. A pharmaceutical composition as claimed in claim 13 , in which the mucolytic is cromoglycate, acetylcysteine, arginine, or 2-mercaptoethanesulphonate.
15. A pharmaceutical composition as claimed in claim 6 which further comprises an anti-inflammatory.
16. A pharmaceutical composition as claimed in claim 15 , in which the anti-inflammatory agent is an inhibitor of tumor necrosis factor alpha (TNFα) or dipeptidyl peptidase IV, and/or antibodies to pro-inflammatory interleukins such as IL4 and IL13.
17. A method for treating bronchoconstriction associated with a reversible obstructive airways disease, which comprises administering to a patient in need of treatment, an effective amount of a compound as claimed in claim 1 .
18. A process for the preparation of a compound as defined in any one of claims 1 to 3 or 4 , which comprises reacting a compound of general formula (II)
in which P 1 represents a hydrogen atom or a hydroxyl protecting group, with a compound of general formula (III)
in which P 2 represents a hydrogen atom or a hydroxyl protecting group and P 3 represents a benzylic amine protecting group, to afford a compound of general formula (IV)
or a salt thereof, followed by removing any protecting groups P 1 , P 2 and P 3 and, if desired, forming a pharmaceutically acceptable acid addition salt.