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US 6,593,497 B1Granted
β2-adrenergic receptor agonists
AssigneeTheravance, Inc.
InventorsSeok-Ki Choi, Edmund J. Moran
Life of this patent
Estimating the term…
Abstract
The present invention is directed to multibinding compounds which are β2 adrenergic receptor agonists and are therefore useful in the treatment and prevention of respiratory diseases such asthma, bronchitis, and the like. They are also useful in the treatment of nervous system injury and premature labor.
Claims8
A compound of Formula (II):
- wherein:
- Ar1 is a phenyl ring of formula (c):
- wherein:
- R4 is hydrogen, alkyl, halo, or alkoxy;.
- R5 is hydrogen, hydroxy, halo, amino, or —NHSO2Ra where Ra is alkyl;
- and
- R6 is hydrogen, halo, alkoxy, substituted alkyl, sulfonylamino, aminoacyl, or acylamino;
- X is selected from the group consisting of -(alkylene)-O—{(alkylene)-O—}n-(alkylene)- (where n is an integer of from 0-9) and further wherein alkylene is —(CH2)6;
- and
- Ar is either:
- (i) a phenyl ring of formula (c′):
- wherein:
- R4 is hydrogen, alkyl, halo, or alkoxy;
- R5 is hydrogen, hydroxy, halo, amino, or —NHSO2Ra where Ra is alkyl;
- and
- R6 is hydrogen, halo, hydroxy, alkoxy, substituted alkyl, sulfonylamino, aminoacyl, or acylamino;
- or
- (ii) a phenyl ring of formula (d):
- wherein:
- R7 is hydrogen, alkyl, alkenyl, substituted alkyl, halo, alkoxy, substituted alkoxy, hydroxy, aminoacyl, or heteroaryl;
- and
- R8 is hydrogen, halo, alkoxy, substituted alkoxy, acylamino;
- or
- (iii) naphthyl, pyridyl, benzimidazol-1-yl, indolyl, 2-cyanoindolyl, carbazolyl, 4-methylindanyl, 5-(CH3CO2CH2O—)-1,2,3,4-tetrahydronaphthyl, 1H-2oxoindole, 2,3,4-trihydrothianaphthalene, or 4-oxo-2,3-dihydrothianapthalene;
- or a pharmaceutically acceptable salt thereof.
22 more elements
A compound of formula II:
- wherein:
- Ar1 is a phenyl ring of formula (c):
- wherein:
- R4 is hydrogen, methyl, fluoro, chloro, methoxy;
- R5 is hydrogen, hydroxy, fluoro, chloro, amino, —NHSO2CH3;
- and
- R6 is hydrogen, chloro, fluoro, methoxy, hydroxymethyl, —CH2SO2CH3, —NHSO2CH3, —NHCHO, —CONH2, —NHCONH2;
- Ar2 is either:
- (i) a phenyl ring of formula (c′):
- wherein:
- R4 is hydrogen, methyl, fluoro, chloro, methoxy;
- R5 is hydrogen, hydroxy, fluoro, chloro, amino, —NHSO2CH3;
- and
- R6 is hydrogen, chloro, fluoro, hydroxy, methoxy, hydroxymethyl, —CH2SO2CH3, —NHSO2CH3, —NHCHO, —CONH2, —NHCONH2;
- or
- (ii) a phenyl ring of formula (d):
- wherein:
- R7 is hydrogen, methyl, propen-2-yl, fluoro, chloro, methoxy, —CH2CO2Me, hydroxy, —CH2CONH2, —NHCOCH3, imidazol-1-yl, or 1-methyl-4-trifluoromethyl-imidazol-2-yl;
- and
- R8 is hydrogen, fluoro, chloro, methoxy, —CH2CO2Me, or —CONH2;
- or
- (iii) naphthyl, pyridyl, benzimidazol-1-yl, indolyl, 2yanoindolyl, carbazolyl, 4-methylindanyl, 5-(CH3CO2CH2O—)-1,2,3,4-tetrahydronaphthyl, 1H-2-oxoindole, 2,3,4-trihydrothianaphthalene, or 4-oxo-2,3-dihydrothianapthalene;
- and
- X is selected from the group consisting of -(alkylene)-O—{(alkylene)-O—}n-(alkylene)- (where n is an integer of from 0-9) and further wherein alkylene is —(CH2)6—.
21 more elements
A compound of Formula (II):
- wherein:
- Ar1 is phenyl, 4-hydroxyphenyl, 3,4-dichlorophenyl, 2chloro-3,5-dihydroxyphenyl, 2-fluoro-3,5-dihydroxyphenyl, 4-hydroxy-3-methoxyphenyl, 4-hydroxy-3-hydroxymethylphenyl, 4-hydroxy-3-(HCONH—)phenyl, 4-hydroxy-3-(NH2CO—)phenyl, 3-chlorophenyl, 2,5direthoxyphenyl, 4-(CH3SO2NH—)-phenyl, 4-hydroxy-3-(CH3SO2CH2—)phenyl, 4-hydroxy-3-(CH3SO2NH—)phenyl, 4-hydroxy-3-(NH2CONH—)phenyl, or 3,5-dichloro-4-aminophenyl;
- X is selected from the group consisting of —(CH2)6—O—(CH2)6— and —(CH2)6—O—(CH2)6—O—(CH2)6—;
- and
- Ar2 is:
- where X′ is selected from the group consisting of hydrogen, methoxy and hydroxyl;
- X″ is selected from the group consisting of hydrogen and cyano;
- Y is selected from the group consisting of hydroxyl, methyl, —C(O)NH2 and —NHC(O)NH2;
- Z is selected from the group consisting of —O— and —CH2—;
- Z′ is selected from the group consisting of chloro and hydrogen;
- and
- Z″ is selected from the group consisting of chloro and fluoro.
9 more elements
A compound of the formula:
- or a pharmaceutically acceptable salt thereof.
A compound of the formula:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.