Phenylethanolamine compounds as β
View Patent ↗The invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein R 1 is H, chlorine, or bromine; R 2 is electron attractive groups selected from the group consisting of CF 3 , CN, fluorine, CH 3 SO 3 , CF 3 SO 3 , and NO 2 ; R 3 is linear or branched alkyl having 1 to 10 carbon atoms, linear or branched alkoxyalkyl having 2 to 10 carbon atoms, aliphatic alcohol having 1 to 10 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms. The invention also relates to methods for preparing the said compounds and the composition comprising the same. The compounds of the present invention have the effect of β 2 -receptor agonist and can be used for the treatment of asthma and bronchitis
1. A compound of formula (I)
wherein:
R 1 is H, chlorine, bromine, iodine, or cyano;
R 2 is an electron attractive group selected from the group consisting of CF 3 , CN, fluorine, COSO 3 H, CF 3 SO 3 , and NO 2 ; and
R 3 is linear or branched alkyl having 1 to 10 carbon atoms, linear or branched alkoxyalkyl having 2 to 10 carbon atoms, aliphatic alcohol having 1 to 10 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms;
or a pharmaceutically acceptable salt thereof.
2. The compound according to claim 1 , wherein R 2 is CF 3 or CN.
3. The compound according to claim 1 , wherein R 3 is linear or branched alkyl having 1 to 6 carbon atoms, linear or branched alkoxy having 2 to 6 carbon atoms, aliphatic alcohol having 1 to 6 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms.
4. The compound according to claim 1 , wherein the pharmaceutically acceptable salt of the compound of formula (I) is a hydrochloride or hydrobromide salt.
5. A method for preparing the compound of claim 1 , comprising
reacting the free alkali of formula (III) or a pharmaceutically acceptable salt thereof
wherein R 1 and R 2 are as defined in claim 1 ,
with a compound of formula (IV)
H 2 NR 3 (IV)
wherein R 3 is as defined in claim 1 .
6. The method according to claim 5 , wherein the reaction of compounds of formula (III) and the compounds of formula (IV) is carried out under an anhydrous condition; the reacting solvent is an alcohol or an aromatic hydrocarbon; the reacting temperature is the refluxing temperature of the reacting solvent; the reacting period is 10–15 hr; and the yield is 20–30%.
7. A pharmaceutical composition comprising the compound according to any one of claims 1 – 4 and a pharmaceutically acceptable excipient.
8. A method of stimulating β 2 -Receptor in a subject in need thereof, comprising:
administering to the subject a compound of formula (I)
wherein:
R 1 is H, chlorine, bromine, iodine, or cyano;
R 2 is an electron attractive group selected from the group consisting of CF 3 , CN, fluorine, COSO 3 H, CF 3 SO 3 , and NO 2 ; and
R 3 is linear or branched alkyl having 1 to 10 carbon atoms, linear or branched alkoxyalkyl having 2 to 10 carbon atoms, aliphatic alcohol having 1 to 10 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms;
or a pharmaceutically acceptable salt thereof.
9. The method according to claim 8 , wherein R 2 is CF 3 or CN.
10. The method according to claim 8 , wherein R 3 is linear or branched alkyl having 1 to 6 carbon atoms, linear or branched alkoxy having 2 to 6 carbon atoms, aliphatic alcohol having 1 to 6 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms.
11. The method according to claim 8 , wherein the pharmaceutically acceptable salt of the compound of formula (I) is a hydrochloride or hydrobromide salt.
12. A method of treating asthma or bronchitis in a subject, comprising:
administering to the subject a pharmaceutically effective amount of a pharmaceutical composition comprising a compound of formula (I)
wherein:
R 1 is H, chlorine, bromine, iodine, or cyano;
R 2 is an electron attractive group selected from the group consisting of CF 3 , CN, fluorine, COSO 3 H, CF 3 SO 3 , and NO 2 ; and
R 3 is linear or branched alkyl having 1 to 10 carbon atoms, linear or branched alkoxyalkyl having 2 to 10 carbon atoms, aliphatic alcohol having 1 to 10 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms;
or a pharmaceutically acceptable salt thereof.
13. The method according to claim 12 , wherein R 2 is CF 3 or CN.
14. The method according to claim 12 , wherein R 3 is linear or branched alkyl having 1 to 6 carbon atoms, linear or branched alkoxy having 2 to 6 carbon atoms, aliphatic alcohol having 1 to 6 carbon atoms, or cycloalkyl having 3 to 6 carbon atoms.
15. The method according to claim 12 , wherein the pharmaceutically acceptable salt of the compound of formula (I) is a hydrochloride or hydrobromide salt.
16. The method according to claim 12 , wherein the compound or its pharmaceutically acceptable salt is administered orally or paraterally.
17. The method according to claim 12 , wherein the compound or its pharmaceutically acceptable salt is administered via inhalation.
18. The method according to claim 12 , wherein the compound or its pharmaceutically acceptable salt is administered to a human subject at a dose of 50 μg-10 mg/day.