PGD2 receptor antagonists for the treatment of inflammatory diseases
View Patent ↗Disclosed herein are compounds represented by Structural Formula (I) and (I-A): Also disclosed is the use of such compounds for inhibiting the G-protein coupled receptor referred to as chemoattractant receptor-homologous molecule expressed on Th2, or simply “CRTH2” for the treatment of inflammatory disorders. The variables in Structural Formula (I) and (I-A) are defined herein.
1. A compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
V is a covalent bond or —O—;
T is an straight chained C 1-10 alkylene substituted with alkyl, gem dialkyl, haloalkyl, spiro cycloalkyl, or an optionally N-substituted nitrogen containing spiro non-aromatic heterocyclic group;
R Y is R Y is —C(O)OR 5 , —C(O)R 5 , —OC(O)R 5 , —C(O)N(R 5 ) 2 , —NR 5 C(O)R 5 , —NR 5 C(O)OR 5 , —S(O) 2 R 5 , —S(O) 2 COR 5 , —S(O) 2 N(R 5 ) 2 , —NR 5 S(O) 2 , —NR 5 S(O) 2 R 5 , S(O) 2 OR 5 , —S(O)OR 5 , —SR 5 , —C(O)NR 5 S(O) 2 R 5 , —CN, —NR 5 C(O)N(R 5 ) 2 , —OC(O)N(R 5 ) 2 , —N(R 5 ) 2 , —OR 5 , an optionally substituted non-aromatic heterocyclic group or an optionally substituted heteroaryl group; and
each R 5 is independently —H, alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, —C(O)OCH 2 C 6 H 5 , S(O) 2 CH 3 , —C(O)OH, —C(O)OMe, —C(O)OEt, C(O)NH 2 , benzyl, pyrrolidinyl, morpholinyl, or —N(R 5 ) 2 is an optionally substituted nitrogen-containing non-aromatic heterocyclic group.
2. A compound represented by the following structural formula:
or a pharmaceutically acceptable salt thereof, wherein:
V is —O—;
T is an straight chained C 1-10 alkylene optionally substituted at any one or more substitutable carbon atoms with halide, alkyl, gem dialkyl, haloalkyl, gem dihalo, haloalkyl, alkoxy, haloalkoxy, spiro cycloalkyl, optionally N-substituted nitrogen containing spiro non-aromatic heterocyclic group, amine , alkylamine, dialkylamine, or hydroxyl;
R Y is —C(O)OR 5 , —C(O)R 5 , —OC(O)R 5 , —C(O)N(R 5 ) 2 , —NR 5 C(O)R 5 , —NR 5 C(O)OR 5 , —S(O) 2 R 5 , —S(O) 2 COR 5 , —S(O) 2 N(R 5 ) 2 , —NR 5 S(O) 2 , —NR 5 S(O) 2 R 5 , S(O) 2 OR 5 , —S(O)OR 5 , —SR 5 , —C(O)NR 5 S(O) 2 R 5 , —CN, —NR 5 C(O)N(R 5 ) 2 , —OC(O)N(R 5 ) 2 , —N(R 5 ) 2 , —OR 5 , an optionally substituted non-aromatic heterocyclic
each R 5 is independently —H, alkyl, haloalkyl, hydroxyalkyl, carboxyalkyl, —C(O)OCH 2 C 6 H 5 , S(O) 2 CH 3 , —C(O)OH, —C(O)OMe, —C(O)OEt, C(O)NH 2 , benzyl, pyrrolidinyl, morpholinyl, or —N(R 5 ) 2 is an optionally substituted nitrogen-containing non-aromatic heterocyclic group.