Methyl- and trifluromethyl-substituted pyrrolopyridine modulators of RORC2 and methods of use thereof
The present invention provides methyl- and trifluoromethyl-substituted pyrrolopyridines, pharmaceutical compositions thereof, methods of modulating RORγ activity and/or reducing the amount of IL-17 in a subject, and methods of treating various medical disorders using such pyrrolopyridines and pharmaceutical compositions thereof.
1. A method of treating a condition in a patient, wherein the condition is selected from the group consisting of plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis, comprising administering to the patient in need of such treatment a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt thereof, wherein,
Y is —CF 3 ;
X is phenyl optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of —CH 3 , —CH 2 CH 3 , —CH 2 OH, —OH, —OCH 3 , —SCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 , —F, —Cl, —Br and —CN;
R 1 is —CH 3 or —CH 2 CH 3 ;
W is
each optionally substituted with one, two, three, four or five —CH 3 ; and
R 2 is (C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, phenyl, tetrahydrothiophenyl, thietanyl or indanyl, optionally substituted with one, two, three, four or five substituents independently selected for each occurrence from the group consisting of —F, —Cl, —Br, —OH, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl and (C 3 -C 10 )cycloalkyl.
2. A method of treating a condition in a patient, wherein the condition is selected from the group consisting of plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis, comprising administering to the patient in need of such treatment a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt, pharmaceutically active metabolite, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof, wherein,
Y is —CH 3 or —CF 3 ;
X is phenyl optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of —CH 3 , —CH 2 CH 3 , —CH 2 OH, —OH, —OCH 3 , —SCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 , —F, —Cl, —Br and —CN;
R 1 is —CH 3 or —CH 2 CH 3 ;
W is
and
R 2 is (C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, phenyl, tetrahydrothiophenyl, thietanyl or indanyl, optionally substituted with one, two, three, four or five substituents independently selected for each occurrence from the group consisting of —F, —Cl, —Br, —OH, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl and (C 3 -C 10 )cycloalkyl.
3. A method of treating a condition in a patient, wherein the condition is selected from the group consisting of plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis, comprising administering to the patient in need of such treatment a therapeutically effective amount of a compound of Formula I:
or a pharmaceutically acceptable salt, pharmaceutically active metabolite, pharmaceutically acceptable prodrug, or pharmaceutically acceptable solvate thereof, wherein,
Y is —CH 3 or —CF 3 ;
X is phenyl optionally substituted with one, two, three, four or five substituents independently selected from the group consisting of —CH 3 , —CH 2 CH 3 , —CH 2 OH, —OH, —OCH 3 , —SCH 3 , —OCH 2 CH 3 , —OCH 2 CH 2 OH, —OCH 2 CH 2 OCH 3 , —F, —Cl, —Br and —CN;
R 1 is —CH 3 or —CH 2 CH 3 ;
W is
and
R 2 is (C 1 -C 6 )alkyl, (C 3 -C 10 )cycloalkyl, phenyl, tetrahydrothiophenyl, thietanyl or indanyl, optionally substituted with one, two, three, four or five substituents independently selected for each occurrence from the group consisting of —F, —Cl, —Br, —OH, (C 1 -C 3 )alkyl, (C 1 -C 3 )haloalkyl and (C 3 -C 10 )cycloalkyl.
4. A method of treating a condition in a patient, wherein the condition is selected from the group consisting of plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis, comprising administering to the patient in need of such treatment a therapeutically effective amount of a compound selected from the group consisting of
and pharmaceutically acceptable salts thereof.
5. A method of treating a condition in a patient, wherein the condition is selected from the group consisting of plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis, comprising administering to the patient in need of such treatment a therapeutically effective amount of a compound of structure
or a pharmaceutically acceptable salt thereof.
6. A method of treating a condition in a patient, wherein the condition is selected from the group consisting of plaque psoriasis, guttate psoriasis, inverse psoriasis, pustular psoriasis, and erythrodermic psoriasis, comprising administering topically to the patient in need of such treatment a therapeutically effective amount of a compound of structure
or a pharmaceutically acceptable salt thereof.
7. A method of treating psoriasis in a patient comprising administering topically to the patient in need of such treatment a therapeutically effective amount of a compound of structure
or a pharmaceutically acceptable salt thereof.