Thromboxane A2 (TP) receptor antagonists
The present invention relates to novel TP receptor antagonists, which optionally cross the blood-brain barrier of a mammal. The invention also provides methods for treating a disorder related to activation of TP receptor utilizing the compounds of the invention.
1. A composition comprising a compound of Formula (I), or a salt or solvate thereof:
wherein:
R 1 is selected from the group consisting of
the bond between carbons 1 and 2 is either a single bond (C 1 -C 2 ) or a double bond (C 1 ═C 2 );
R 2 is selected from the group consisting of F, Cl, Br, I, and CF 3 ;
R 3 is selected from the group consisting of NR 4 , S, and O;
R 4 is selected from the group consisting of H, —(C 1 -C 6 alkyl), —(C 1 -C 6 fluoroalkyl), —(C 1 -C 6 heteroalkyl), —(C 1 -C 3 alkyl)-(C 3 -C 6 cycloalkyl), —(C 1 -C 3 alkyl)-aryl, —(C 1 -C 3 alkyl)-heteroaryl, —C(═O)R 5 , —CO 2 R 5 , and —CH(R) 2 ; and,
each occurrence of R 5 is independently selected from the group consisting of H, —(C 1 -C 6 alkyl), —(C 1 -C 6 heteroalkyl), and —(C 1 -C 3 alkyl)-(C 3 -C 6 cycloalkyl), wherein the alkyl, heteroalkyl, or cycloalkyl group is optionally substituted.
2. The composition of claim 1 , wherein the compound is selected from the group consisting of 4-chloro-N-(5-(2-(oxazol-2-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)benzenesulfonamide, 4-chloro-N-(5-(2-(thiazol-2-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)benzenesulfonamide, 4-chloro-N-(5-(2-(2-methylthiazol-4-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)benzenesulfonamide, 4-chloro-N-(5-(2-(oxazol-4-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)benzenesulfonamide, N-(5-(2-(1H-imidazol-2-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)-4-chlorobenzenesulfonamide, N-(5-(2-(1H-imidazol-5-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)-4-chlorobenzenesulfonamide, 4-fluoro-N-(5-(2-(thiazol-2-yl)ethyl)-1,2,3,4-tetrahydronaphthalen-2-yl)benzenesulfonamide, a salt thereof, a solvate thereof, and any combinations thereof.