Indole acetic acids exhibiting CRTH2 receptor antagonism and uses thereof

1. A compound having Formula II:

or a pharmaceutically acceptable salt, ester or amide thereof, where said ester is derived from a C 1-6 alcohol and said amide is derived from a C 1-6 amine,

wherein:

the dotted line is a single or double bond;

R 1 is selected from H, optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted C 2-10 alkynyl, optionally substituted C 1-10 alkylaryl, optionally substituted C 1-10 alkylheteroaryl, optionally substituted —C 1-10 alkyl-O—C 1-10 alkyl, optionally substituted —C 1-10 alkyl-O-aryl, optionally substituted —C 1-10 alkyl-O-heteroaryl, optionally substituted aryl, and optionally substituted heteroaryl;

R 2 , R 2a , R 3 and R 3a are independently selected from H, halogen, and C 1-10 alkyl, wherein R 2a and R 3a are present only when the carbons to which they are attached are saturated; or R 2 and R 3 taken together with the carbon atoms to which they are attached, form an optionally substituted saturated, unsaturated, or aromatic 5- or 6-membered ring; or R 2 and R 2a taken together with the carbon atoms to which they are attached, form an optionally substituted saturated 3-6 membered ring;

R 4 is H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, or halogen, wherein R 4 is present only when the carbon to which it is attached is saturated;

R 5 is H, C 1-10 alkyl, perhaloalkyl, C 2-10 alkenyl, C 2-10 alkynyl, C 1-10 alkylaryl, C 1-10 alkylheteroaryl, aryl, or heteroaryl, wherein said aryl or heteroaryl is optionally substituted with one or more substituents selected from C 1-10 alkyl, halogen, C 1-10 alkoxy, and CN;

R 6 is one or more H, halogen, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, CN, OR 7 , SR 7 , aryl or heteroaryl groups; and

R 7 is H, C 1-10 alkyl, C 2-10 alkenyl, C 2-10 alkynyl, aryl, or heteroaryl,

wherein unless otherwise specified, optional substituents are selected from C 1-10 alkyl, halogen, halo C 1-10 alkyl, halo C 1-10 alkoxy, cycloalkyl, hydroxy, cyano, aryl, aryloxy, carbamoyl, aralkyl, heteroaryl, heteroaryloxy, alkoxycarbonyl, amino, acyloxy, arylacyloxy, heterocyclo, heterocycloalkoxy, partially unsaturated heterocycylalkyl and partially unsaturated heterocyclylalkoxy, and where each optional substituent may be further substituted with one or more C 1-6 alkyl, halogen, halo C 1-10 alkyl, C 1-10 alkoxy, haloalkoxy, aryl, or heteroaryl groups.

2. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt, ester or amide thereof, and a pharmaceutically acceptable carrier.

3. The compound of claim 1 , or a pharmaceutically acceptable salt, ester or amide thereof, wherein:

R 1 is selected from hydrogen, optionally substituted C 1-10 alkyl, optionally substituted C 2-10 alkenyl, optionally substituted aryl, optionally substituted C 1-10 alkylheteroaryl, optionally substituted C 1-10 alkylaryl, optionally substituted —C 1-10 alkyl-O—C 1-10 alkyl, and optionally substituted —C 1-10 alkyl-O-aryl;

R 4 is H or C 1-10 alkyl;

R 5 is H or C 1-10 alkyl; and

R 6 is selected from H, halogen, C 1-10 alkoxy, CN, and C 1-10 alkyl.

4. The compound of claim 3 , or a pharmaceutically acceptable salt, ester or amide thereof, wherein R 1 is selected from hydrogen, methyl, benzyl, isopentyl, quinoline-2-yl-methyl, 3-(4-fluorphenoxy)-benzyl, biphenyl-2-ylmethyl, 2-thiophen-2-yl-thiazol-4-ylmethyl, 2-(4-chlorophenyl)-thiazol-4-ylmethyl, 3,5-dimethyl-isoxazol-4-ylmethyl, 5-methyl-3-phenyl-isoxazol-4-ylmethyl, (4-fluorophenylcarbamoyl)methyl, 2-hydroxyethyl, (4-chlorophenoxy)ethyl, 2-ethoxycarbonylmethyl, 2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl, 2-methyl-thiazol-4-ylmethyl, 3-trifluoromethylbenzyl, 2-allyl, 3-phenoxypropyl, isopropyl, 2-benzothiazol-2ylmethyl, 4-fluorobenzyl, 3-benzyloxy-propyl, 3-methoxypropyl, cyano-methylmethyl, 2-phenethyl, 1-methyl-2-phenyl-ethyl, 4-cyanobenzyl, 3-fluorobenzyl, 2-phenoxyethyl, and phenyl.

5. The compound of claim 3 or a pharmaceutically acceptable salt, ester, or amide thereof, wherein R 2 and R 3 , taken together with the carbon atoms to which they are attached, form an optionally substituted saturated, unsaturated or aromatic 5- or 6-membered ring.

6. The compound of claim 5 or a pharmaceutically acceptable salt, ester, or amide thereof, wherein R 2 and R 3 , taken together with the carbon atoms to which they are attached, form a benzene ring optionally substituted with one or more halogens.

7. The compound of claim 3 or a pharmaceutically acceptable salt, ester, or amide thereof, wherein R 4 is H or methyl.

8. The compound of claim 3 or a pharmaceutically acceptable salt, ester, or amide thereof, wherein R 5 is H or methyl.

9. The compound of claim 3 or a pharmaceutically acceptable salt, ester, or amide thereof, wherein R 6 is selected from H, methyl, methoxy, bromo, chloro, fluoro, and CN.