Treatment of respiratory disorders using ROR-gamma inhibitors
The present patent application relates to treatment of a respiratory disorder using retinoid-related orphan receptor gamma t (ROR-gamma) modulators. Particularly, the present patent application relates to treatment of a respiratory disorder using a RORγ inhibitor, wherein the RORγ inhibitor is administered by an inhalation route to a subject in need thereof.
1. A method of treating chronic obstructive pulmonary disease (COPD) in a subject, the method comprising administering to the subject an effective amount of a RORγ inhibitor by inhalation route, wherein the RORγ inhibitor is selected from compounds of formula (I)
or a pharmaceutically acceptable salt thereof, wherein,
Ring A is
X 1 and X 4 , which may be same or different, are each independently selected from N, CH and CR 1 ;
Ring B is selected from phenyl, pyridinyl, benzimidazolyl, indolyl, [1,2,4]triazolo[4,3-a]pyridinyl and [1,2,4]oxadiazolyl;
is selected from
x, y and z represents point of attachment;
R is selected from C 1-8 alkyl and haloC 1-8 alkyl;
each occurrence of R 1 is independently selected from halogen, cyano, hydroxyl and C 1-8 alkyl;
each occurrence of R 2 is independently selected from halogen, cyano, hydroxyl, C 1-8 alkyl, C 1-8 alkoxy, haloC 1-8 alkyl, haloC 1-8 alkoxy, hydroxyC 1-8 alkyl, C 3-6 cycloalkyl, C 3-6 cycloalkylC 1-8 alkyl and 4-chloro-phenyl;
each occurrence of R 3 is independently selected from halogen, cyano, hydroxyl and C 1-4 alkyl;
R 4 is selected from hydrogen, —(CH 2 ) 2 N(CH 3 ) 2 , C 1-8 alkyl, haloC 1-8 alkyl, C 3-6 cycloalkyl and C 3-6 cycloalkylC 1-8 alkyl;
each occurrence of R 5 is independently selected from halogen, cyano, hydroxyl and C 1-8 alkyl;
each occurrence of R a and R b , which may be same or different, are each independently selected from halogen, C 1-8 alkyl, haloC 1-8 alkyl and C 1-8 alkoxy; or R a and R b together with the carbon atom to which they are attached, form a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, tetrahydro-2H-pyran-4-yl, oxetan-3-yl, N-methyl-piperidin-4-yl or piperidin-4-yl ring;
each occurrence of R c and R d , which may be same or different, are each independently selected from hydrogen, C 1-8 alkyl, haloC 1-8 alkyl and C 1-8 alkoxy; or R c and R d together with the carbon atom to which they are attached, form a C 3-6 cycloalkyl ring;
R e is selected from C 1-8 alkyl, haloC 1-8 alkyl and C 3-6 cycloalkyl;
‘n’ is 0, 1, 2 or 3;
‘p’ is 0, 1 or 2;
‘q’ is 1 or 2;
‘s’ is 1, 2 or 3;
‘t’ is 0, 1 or 2; and
‘u’ is 1 or 2.
2. The method according to claim 1 , wherein the RORγ inhibitor is Compound 1, structurally represented as
or a pharmaceutically acceptable salt thereof.
3. A method of treating COPD in a subject, said method comprising administering to the subject an effective amount of a RORγ inhibitor by inhalation route, wherein the RORγ inhibitor is Compound 1, structurally represented as
or a pharmaceutically acceptable salt thereof.
4. The method according to claim 1 , wherein the RORγ inhibitor is Compound 9, structurally represented as
or a pharmaceutically acceptable salt thereof.
5. A method of treating COPD in a subject, said method comprising administering to the subject an effective amount of a RORγ inhibitor by inhalation route, wherein the RORγ inhibitor is Compound 9, structurally represented as
or a pharmaceutically acceptable salt thereof.