Indole derivatives as CRTH2 receptor antagonists
View Patent ↗Compounds according to formula (I) wherein the radicals R 1 , R 2 and R 3 are as herein defined, and wherein Ar represents an aryl group or heteroaryl group, preferably phenyl, n is 1 or 2, and the radical X represents a group selected from —C(R a )(R b )—, —C(R a )(R b )—C(R a )(R b )—, —C(R a )═C(R a )—, OC(R a )(R b )— or SC(R a )(R b )—. These compounds and their pharmaceutical acceptable salts are used in pharmaceutical compositions as prostaglandine D2 receptor antagonists useful in the treatment of CRTH2-mediated diseases such as respiratory, inflammatory or allergic conditions among others.
1. A compound of the formula I:
and pharmaceutically acceptable salts thereof, wherein:
n is 1 or 2;
Ar is aryl or heteroaryl each optionally substituted with 1 to 4 groups independently selected from R c ;
X is selected from —C(R a )(R b )—, —C(R a )(R b )—C(R a )(R b )—, —C(R a )═C(R a )—, —OC(R a )(R b )—, and —SC(R a )(R b )—;
R 1 is selected from H, halogen and C 1-6 alkyl;
R 2 is selected from H and C 1-6 alkyl;
R 3 is selected from H, halogen, C 1-6 alkyl, OC 1-6 alkyl, SC 1-6 6alkyl, S(O) n C 1-6 alkyl, CN, aryl and heteroaryl;
R a and R b are independently H, halogen, aryl, heteroaryl, C 1-6 alkyl or haloC 1-6 alkyl; or
R a and R b together with the carbon atom to which they are both attached complete a C 3-6 cycloalkyl ring; or
R a and R b together with the adjacent carbon atoms to which they are attached complete a C 3-6 cycloalkyl ring; and
R c is selected from halogen, CN, C 1-6 alkoxy, C 1-6 alkyl, haloC 1-6 alkoxy, and haloC 1-6 alkyl.
2. A compound of claim 1 wherein n is 1.
3. A compound of claim 1 wherein n is 2.
4. A compound of claim 1 wherein Ar is phenyl optionally substituted with 1 to 3 groups independently selected from R c .
5. A compound of claim 1 wherein Ar is phenyl substituted with 1 to 2 groups independently selected from halogen and C 1-6 alkoxy.
6. A compound of claim 1 wherein X is —C(R a )(R b )—.
7. A compound of claim 1 wherein X is methylene.
8. A compound of claim 1 wherein X is —C(R a )(R b )—C(R a )(R b )— or —C(R a )═C(R a )—.
9. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
10. The compound {7-[[(4-fluorophenyl)sulfonyl](methyl)amino]-6,7,8,9-tetrahydropyrido[1,2-a]indol-10-yl}acetic acid or a pharmaceutically acceptable salt thereof.