Chemical Compounds
AssigneeGlaxoSmithKline Intellectual Property Development Limited
InventorsRodolfo Cadilla, David Norman Deaton, Andrew L. Larkin, Christie Schulte, Terrence L. Smalley
Life of this patent
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Abstract
A compound of formula (I), wherein Ar1, R21, R23, R24, R25, R26, R27, A, X, Y and W are as defined herein. The compounds of the present invention are inhibitors of hematopoietic prostaglandin D synthase (H-PGDS) and can be useful in the treatment of Duchenne muscular dystrophy. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting H-PGDS activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.
Claims18
A compound according to Formula (I)
- wherein:
- Ar1 is selected from:
- phenyl, benzofuranyl, pyrazolyl, imidazolyl, pyridinyl, and pyrimidinyl, each of which is optionally substituted with from 1 to 4 substituents independently selected from:
- fluoro,
- chloro,
- bromo,
- iodo,
- C1-3alkyl,
- C1-3alkyl substituted with from one to four substituents independently selected from:
- —OH, oxo, and fluoro,
- —CN,
- —OH,
- cyclopropyl,
- C1-3alkoxy, and
- C1-3alkoxy substituted with from one to four substituents independently selected from:
- —OH, oxo, and fluoro;
- W is selected from:
- S and Se,
- X is selected from:
- C and N;
- Y is selected from:
- —C(O)—, —C(S)—, —C(Se)—, —S(O)—, and —S(O2)—;
- A is selected from:
- —C(O)—, —C(S)—, —C(Se)—, and —S(O2)—;
- R21 is selected from:
- hydrogen and —CH3;
- R23 and R24 are attached to the same or different carbon atoms and are independently selected from:
- hydrogen,
- C1-5alkyl,
- C1-5alkyl substituted with from one to four substituents independently selected from:
- —OH, oxo, —NH2 and fluoro, or
- R23 and R24 are attached to the same carbon and are taken together to form:
- cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuran, or tetrahydropyran, or
- R23 and R24 are attached to different carbon atoms and are taken together to form:
- cyclopropyl, cyclobutyl, cyclopentyl, oxetanyl, tetrahydrofuran, or tetrahydropyran;
- R25 is selected from:
- hydrogen,
- C1-5alkyl,
- C1-5alkyl substituted with from one to four substituents independently selected from:
- —OH, oxo, —NH2 and fluoro, and
- C1-5alkylaryl, and
- C1-5alkylaryl substituted with from 1 to 3 substituents independently selected from
- fluoro,
- chloro,
- bromo,
- iodo,
- C1-3alkyl,
- C1-3alkyl substituted with from one to four substituents independently selected from:
- —OH, oxo, and fluoro,
- —CN,
- —OH,
- cyclopropyl,
- C1-3alkoxy, and
- C1-3alkoxy substituted with from one to four substituents independently selected from:
- —OH, oxo, and fluoro;
- R26 is selected from:
- hydrogen and —CH3;
- and
- R27 is absent when X is N or selected from:
- hydrogen and —CH3;
- or a pharmaceutically acceptable salt thereof.
A compound which is (S)-2-(3-Chloro-5-fluorophenyl)-N-(5,5-dimethyl-2-oxopyrrolidin-3-yl)thiazole-5-carboxamide.
A compound which is
-11. (canceled)
-19. (canceled)
(canceled)
-25. (canceled)
Dependencies are inferred from the claim text.