β2-adrenergic receptor agonists
View Patent ↗Disclosed are multibinding compounds which are β2-adrenergic receptor agonists and are useful in the treatment and prevention of respiratory diseases such as asthma, bronchitis. They are also useful in the treatment of nervous system injury and premature labor.
1. A compound of formula (II):
wherein
Ar 1 is selected from 4-hydroxy-3-hydroxymethylphenyl, 4-hydroxy-3-(HCONH—)phenyl, 3,5-dichloro-4-aminophenyl, and
W is selected from a covalent bond, methylene, ethylene, propylene, —(CH 2 ) 6 —O—(CH 2 ) 3 —, —(CH 2 ) 6 —O—, and —CH 2 CH(OH)CH 2 —O—;
Ar 2 is 1,4-phenylene;
X is a bond;
Q is selected from the group consisting of:
—NH—CH 2 —*CH(OH)—;
—NH—*CH(CH 2 OH)—;
—(CH 2 ) 3 —O—(CH 2 ) 6 —NH—CH 2 —*CH(OH)—; and
—NH—CH 2 —*CH(OH)—CH 2 —O—;
(where * is R or S stereochemistry); and
Ar 3 is phenyl or 4-hydroxy-3-hydroxymethylphenyl;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein W is ethylene.
3. The compound of claim 1 , wherein Q is —NH—CH 2 —*CH(OH)—.
4. The compound of claim 1 , wherein Ar 1 is 4-hydroxy-3-(HCONH—)phenyl.
5. The compound of claim 1 , wherein Ar 3 is phenyl.
6. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of any one of claims 1 to 5 .
7. A pharmaceutical composition for use in a dry powder inhaler, the composition comprising a therapeutically effective amount of a compound of any one of claims 1 to 5 ; and lactose.
8. A method of treating asthma in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound of any one of claims 1 to 5 .
9. A method of agonizing a ∃ 2 adrenergic receptor, the method comprising contacting the ∃ 2 adrenergic receptor with a compound of any one of claims 1 to 5 .