Cycloalkyl-fused tetrahydroquinolines as CRTH

1. A compound of the Formula (I)

or a pharmaceutically acceptable salt or ester thereof, wherein

R 1 is

(i) H,

(ii) C 1 -C 4 alkyl,

(iii) C 2 -C 4 alkenyl,

(iv) C 3 -C 7 cycloalkyl,

(v) —(C 1 -C 3 alkylene)-R 9 wherein R 9 is C 3 -C 7 cycloalkyl, phenyl or a 5- to 6-membered heteroaryl containing 1 to 2 heteroatoms selected from the group consisting of N, O, and S,

(vi) phenyl,

(vii) —C(O)—R 5 , wherein R 5 is C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, phenyl,

(viii) or a group of the formula

 wherein v is 1, 2, or 3;

R 2 is

(i) -Q-W—V, wherein

Q is —C(O)—, —C(O)O—, —C(O)N(H)—, —C(O)N(C 1 -C 6 alkyl)-, —CH 2 —, or —S(O) 2 —;

W is

(a) C 1 -C 8 alkylene, wherein said alkylene of W is unsubstituted or substituted by 1 to 2 fluoro;

(b) —CH═CH—, or

(c) a phenylene of the formula

 wherein said phenylene is unsubstituted or substituted by 1 to 2 halo;

V is

(a) —CO 2 H,

(b) tetrazolyl, or

(c) a group of the formula

 wherein R V1 is selected from the group consisting of C 1 -C 6 alkyl, C 3 -C 6 cycloalkyl, and phenyl;

(ii) -M-CO 2 H, wherein

M is

 wherein w is 0, 1, 2, or 3;

X A is S or O;

X B is N or C(H);

with the proviso that when R 1 is —C(O)—R 5 , then R 2 is —CH 2 —W—V;

Y is —C(O)—, —S(O) 2 —, or a group of the formula

wherein X A1 is S or O; and

X B1 is N or C(H);

Z is

(i) absent,

(ii) —(C 1 -C 6 ) alkylene-,

(iii) —O—,

(iv) —O—(C 1 -C 6 alkylene)-, wherein said —O—(C 1 -C 6 alkylene)- of Z is unsubstituted or substituted by 1 to 3 fluoro,

(v) —N(H)—, or

(vi) a group of the formula

 wherein r is 1, 2, 3, or 4;

E is

(i) phenyl,

(ii) naphthyl,

(iii) tetrahydronapthyl,

(iv) indanyl,

(v) 5- to 10-membered mono- or bicyclic heteroaryl containing one to three heteroatoms selected from the group consisting of N, O, and S,

(vi) 5- to 10-membered mono- or bicyclic heterocyclenyl containing one to three heteroatoms selected from the group consisting of N, O, and S,

wherein said phenyl, napthyl, tetrahydronapthyl, indanyl, 5- to 10-membered heteroaryl, or 5- to 10-membered heterocyclenyl of E is unsubstituted or substituted by one to three R 4 moieties, wherein

each R 4 is selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 3 alkoxy, —CN, halo, hydroxyl, C 1 -C 3 fluoroalkyl, —O—(C 1 -C 3 fluoroalkyl), —S—(C 1 -C 3 alkyl), —S—(C 1 -C 3 fluoroalkyl), C 3 -C 7 cycloalkyl, R 4a , —O—R 4a , or 5- to 6-membered heterocyclyl containing 1 or 2 heteroatom selected from the group consisting of N, O, and S;

R 4a is phenyl or a 5 to 6-membered heteroaryl ring containing one to two heteroatoms selected from the group consisting of N, O, and S;

 wherein R 4a is unsubstituted or substituted by one to two moieties independently selected from the group consisting of C 1 -C 6 alkyl, C 1 -C 3 alkoxy, halo, —CN, C 1 -C 3 fluoroalkyl, —O—(C 1 -C 3 fluoroalkyl), —S—(C 1 -C 3 fluoroalkyl), and —SO 2 —(C 1 -C 3 alkyl),

or, wherein two R 4 moieties are substituted on vicinal carbon atoms of E, the two R 4 moieties together with the carbon atoms to which they are attached form a dioxolane ring;

(vii) C 3 -C 7 cycloalkyl, or

(viii) C 1 -C 6 alkyl,

n is 0, 1, or 2;

each occurrence of R 7 is independently halo, C 1 -C 3 fluoroalkyl, hydroxy(C 1 -C 3 alkyl), —CN, phenyl, or a 5- to 6-membered heteroaryl containing 1 to 2 heteroatoms selected from the group consisting of N, O, and S, wherein said phenyl or heteroaryl of R 7 is independently unsubstituted or substituted with 1 to 2 halo;

t is 0, 1, 2, or 3;

each occurrence of R 8 is independently C 1 -C 3 alkyl, C 2 -C 3 alkenyl, or fluoro;

u is 0, 1, or 2; and

R 8a is H or C 1 -C 6 alkyl.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 is

-Q-W—V;

Q is —C(O)—, —C(O)O—, —C(O)N(CH 3 )— or —CH 2 —;

W is C 1 -C 4 alkylene; and

V is —CO 2 H.

3. The compound of claim 2 or a pharmaceutically acceptable salt thereof, wherein the group -Q-W—V is selected from the group consisting of:

4. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is C 1 -C 4 alkyl, C 3 -C 7 cycloalkyl, —CH 2 —(C 3 -C 7 cycloalkyl), or phenyl.

5. The compound of claim 4 or a pharmaceutically acceptable salt thereof, wherein R 1 is methyl, ethyl, cyclopropyl, cyclobutyl, —CH 2 -cyclopropyl, or phenyl.

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein Y is —C(O)— or

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein Y is —C(O)—.

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein the group —Y—Z is selected from the group consisting of —C(O)—, —C(O)O—CH 2 —, —C(O)O—C(H)(CH 3 )—, and

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein E is phenyl, thienyl,

wherein E is unsubstituted or substituted by one to two moieties independently selected from the group consisting of methyl, fluoro, trifluoromethoxy, —O-phenyl, and thiazolyl.

10. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound has the Formula (IB)

wherein

R 1 is H, C 1 -C 4 alkyl, cyclopropyl, cyclobutyl, —CH 2 -cyclopropyl, —CH 2 -cyclobutyl, or phenyl;

Q is —C(O)—, —C(O)O—, —C(O)N(CH 3 )—, or —CH 2 —;

m is 1 or 2;

Y is —C(O)— or

Z is absent, —(C 1 -C 3 ) alkylene-, —OCH 2 —, —OCH(CH 3 )—, or a group of the formula

E is phenyl, thienyl,

wherein E is unsubstituted or substituted by one to two R 4 moieties independently selected from the group consisting of C 1 -C 3 alkyl, fluoro, trifluoromethoxy, —S—CF 3 , —O-phenyl, and thiazolyl;

n is 0 or 1;

each occurrence of R 7 is independently chloro or fluoro; and

t is 0, 1, or 2.

11. The compound of claim 10 or a pharmaceutically acceptable salt thereof, wherein the compound has the Formula (IC)

wherein

Q is —C(O)—, —C(O)O—, or —CH 2 —;

m is 1 or 2;

Z is absent or —OCH 2 —;

each occurrence of R 4 is independently C 1 -C 3 alkyl, fluoro, trifluoromethoxy, or —S—CF 3 ;

v is 0, 1, or 2;

n is 0 or 1;

each occurrence of R 7 is independently chloro or fluoro; and

t is 0, 1, or 2.

12. The compound of claim 11 or a pharmaceutically acceptable salt thereof, wherein the group

is selected from the group consisting of:

13. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

4-[{cis,cis-4-[(Benzyloxy)carbonyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl}(cyclopropyl)amino]-4-oxobutanoic acid;

4-[{cis,cis-4-[(benzyloxy)carbonyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl}(phenyl)amino]-4-oxobutanoic acid;

4-{ethyl[cis,cis-4-{[4-(trifluoromethoxy)phenyl]carbonyl}-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl]amino}-4-oxobutanoic acid;

4-{cyclopropyl[cis,cis-4-{[4-(trifluoromethoxy)phenyl]carbonyl}-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl]amino}-4-oxobutanoic acid;

4-[{cis,cis-4-[(benzyloxy)carbonyl]-6-fluoro-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl}(cyclopropyl)amino]-4-oxobutanoic acid;

4-{cyclopropyl[cis,cis-6-fluoro-4-[(4-phenoxyphenyl)carbonyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl}amino)-4-oxobutanoic acid;

4-{cyclopropyl[cis,cis-3-{[4-(trifluoromethoxy)phenyl]carbonyl}-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl]amino}-4-oxobutanoic acid;

({cyclopropyl[cis,cis-4-{[4-(trifluoromethoxy)phenyl]carbonyl}-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl]carbamoyl}oxy)acetic acid;

3-(phenylmethyl)cis,cis-8-[(3-carboxy-1-oxopropyl)cyclopropylamino]-5-fluoro-2,2a,8,8a-tetrahydrocyclobuta[b]quinoline-3(1H)-carboxylate;

4-(phenylmethyl)cis,cis-9-[(3-carboxy-1-oxopropyl)cyclopropylamino]-6-chloro-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

4-(phenylmethyl)cis,cis-9-[(3-carboxy-1-oxopropyl)cyclopropylamino]-7-fluoro-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

4-[cyclopropyl[(cis,cis)-7-fluoro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid;

4-[[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]methylamino]-4-oxobutanoic acid;

4-[(cyclobutylmethyl)[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid;

4-[cyclopropyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-(3-phenoxybenzoyl)-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxo-butanoic acid;

4-(cyclopropyl(cis,cis-4-(thiophene-2-carbonyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid;

[[[[cis,cis-6-chloro-7-fluoro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]cyclopropylamino]carbonyl]oxy]acetic acid;

4-[cyclopropyl[cis,cis-5-fluoro-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid;

deuterated-4-[cyclopropyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9(R)-yl-(d)]amino]-4-oxobutanoic acid;

4-[[(cis,cis)-6-chloro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]cyclobutylamino]-4-oxobutanoic acid;

4-[[(cis,cis)-6-chloro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]cyclopropylamino]-4-oxobutanoic acid;

4-[[(cis,cis)-6-chloro-2,3,3a,4,9,9a-hexahydro-4-[(trans-2-phenylcyclopropyl)carbonyl]-1H-cyclopenta[b]quinolin-9-yl]cyclopropylamino]-4-oxobutanoic acid;

4-[cyclobutyl[(cis,cis)-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid;

4-[[(cis,cis)-6-chloro-2,3,3a,4,9,9a-hexahydro-4-[(1,2,3,4-tetrahydro-1-naphthalenyl)carbonyl]-1H-cyclopenta[b]quinolin-9-yl]cyclopropylamino]-4-oxobutanoic acid;

4-[[(cis,cis)-6-chloro-4-[(2,3-dihydro-1H-inden-2-yl)carbonyl]-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl]cyclopropylamino]-4-oxobutanoic acid;

4-[[(cis,cis)-6-chloro-2,3,3a,4,9,9a-hexahydro-4-[(1,2,3,4-tetrahydro-2-naphthalenyl)carbonyl]-1H-cyclopenta[b]quinolin-9-yl]cyclopropylamino]-4-oxobutanoic acid;

4-[cyclopropyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[3-(5-thiazolyl)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid;

4-[(2,4-difluorophenyl)methyl](cis,cis)-9-[[(carboxymethoxy)carbonyl]cyclopropylamino]-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

4-[1-(4-fluorophenyl)ethyl](cis,cis)-9-[(3-carboxy-1-oxopropyl)cyclopropylamino]-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

4-(1,2,3,4-tetrahydro-2-naphthalenyl)(cis,cis)-9-[(3-carboxy-1-oxopropyl)cyclopropylamino]-7-fluoro-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

4-[cyclopropyl[(cis,cis)-6-fluoro-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid;

3-(phenylmethyl)(cis,cis)-8-[(3-carboxy-1-oxopropyl)cyclopropylamino]-5-chloro-2,2a,8,8a-tetrahydrocyclobuta[b]quinoline-3(1H)-carboxylate;

4-[[(cis,cis)-5-chloro-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]cyclopropylamino]-4-oxobutanoic acid;

3-(phenylmethyl)(cis,cis)-8-[(3-carboxy-1-oxopropyl)cyclopropylamino]-2,2a,8,8a-tetrahydrocyclobuta[b]quinoline-3(1H)-carboxylate;

4-[cyclopropyl[(cis,cis)-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid;

4-(phenylmethyl)(cis,cis)-9-[[(carboxymethoxy)carbonyl]cyclopropylamino]-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

4-(phenylmethyl)(cis,cis)-9-[[(carboxymethoxy)carbonyl]cyclopropylamino]-7-fluoro-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

[[[cyclopropyl[cis,cis)-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]carbonyl]oxy]acetic acid;

[[[cyclopropyl[cis,cis)-3-(3,4-difluorobenzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl]amino]carbonyl]oxy]acetic acid;

[[[cyclopropyl[(cis,cis)-7-fluoro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]carbonyl]oxy]acetic acid;

4-(phenylmethyl)(cis,cis)-9-[[(2(S)-carboxy-1-azetidinyl)carbonyl]cyclopropylamino]-1,2,3,3a,9,9a-hexahydro-4H-cyclopenta[b]quinoline-4-carboxylate;

N-[[cyclopropyl[(cis,cis)-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]carbonyl]-N-methylglycine;

[[[cyclopropyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[5-[[4-(trifluoromethoxy)phenyl]methyl]-1,3,4-oxadiazol-2-yl]-1H-cyclopenta[b]quinoline-9-yl]amino]carbonyl]oxy]acetic acid;

2-[ethyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxazolecarboxylic acid;

3-(phenylmethyl)cis,cis-8-[(3-carboxypropyl)cyclopropylamino]-5-fluoro-2,2a,8,8a-tetrahydrocyclobuta[b]quinoline-3(1H)-carboxylate;

4-[cyclopropyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]butanoic acid;

4-[cyclopropyl[cis,cis-5-fluoro-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]butanoic acid;

4-[cyclopropyl[(cis,cis)-2,3,3a,4,9,9a-hexahydro-4-[4-[(trifluoromethyl)thio]benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid;

4-(ethyl((cis,cis)-3-(4-(trifluoromethylthio)benzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)amino)-4-oxobutanoic acid;

4-(ethyl((cis,cis)-3-(4-ethylbenzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)amino)-4-oxobutanoic acid;

3-(phenylmethyl) 8-[(3-carboxy-1-oxopropyl)cyclopropylamino]-5,6-difluoro-2,2a,8,8a-tetrahydro-cyclobuta[b]quinoline-3(1H)-carboxylate;

4-[cyclopropyl[(cis,cis)-5,6-dichloro-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid;

4-(cyclopropyl((cis,cis)-5,6-difluoro-3-(4-(trifluoromethoxy)benzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)amino)-4-oxobutanoic acid;

4-[cyclopropyl[(cis,cis)-6-fluoro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxo-butanoic acid;

(R)-1-(((cis,cis)-3-(benzyloxycarbonyl)-5,6-difluoro-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)(cyclopropyl)carbamoyl)azetidine-2-carboxylic acid;

4-(cyclopropyl(cis,cis-3-(4-((trifluoromethyl)thio)benzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)amino)-4-oxobutanoic acid;

4-(ethyl(cis,cis-6-fluoro-3-(4-((trifluoromethyl)thio)benzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)amino)-4-oxobutanoic acid;

4-(ethyl(cis,cis-7-fluoro-4-(4-((trifluoromethyl)thio)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid;

4-(cyclopropyl(cis,cis-7-fluoro-4-(4-((trifluoromethyl)thio)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid; and

4-(cyclopropyl(cis,cis-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)butanoic acid.

14. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of:

4-{cyclopropyl[cis,cis-4-{[4-(trifluoromethoxy)phenyl]carbonyl}-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl]amino}-4-oxobutanoic acid;

4-[cyclopropyl[cis,cis-7-fluoro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid;

4-[[cis,cis-6-chloro-7-fluoro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]cyclopropylamino]-4-oxobutanoic acid;

4-[cyclopropyl[cis,cis-5-fluoro-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid;

4-[cyclopropyl[cis,cis-6-fluoro-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid;

3-(phenylmethyl)(cis,cis)-8-[(3-carboxy-1-oxopropyl)cyclopropylamino]-5-chloro-2,2a,8,8a-tetrahydrocyclobuta[b]quinoline-3(1H)-carboxylate;

3-(phenylmethyl)(cis,cis)-8-[(3-carboxy-1-oxopropyl)cyclopropylamino]-2,2a,8,8a-tetrahydrocyclobuta[b]quinoline-3(1H)-carboxylate;

4-[cyclopropyl[cis,cis-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid;

[[[cyclopropyl[cis,cis-3-(3,4-difluorobenzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl]amino]carbonyl]oxy]acetic acid;

3-(phenylmethyl)cis,cis-8-[(3-carboxypropyl)cyclopropylamino]-5-fluoro-2,2a,8,8a-tetrahydrocyclobuta[b]quinoline-3(1H)-carboxylate;

4-[cyclopropyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]butanoic acid;

4-[cyclopropyl[cis,cis-2,3,3a,4,9,9a-hexahydro-4-[4-[(trifluoromethyl)thio]benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid;

(R)-1-((cis,cis-3-(benzyloxycarbonyl)-5,6-difluoro-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)(cyclopropyl)carbamoyl)azetidine-2-carboxylic acid;

4-(cyclopropyl(cis,cis-3-(4-((trifluoromethyl)thio)benzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)amino)-4-oxobutanoic acid;

4-(ethyl(cis,cis-6-fluoro-3-(4-((trifluoromethyl)thio)benzoyl)-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)amino)-4-oxobutanoic acid;

4-(ethyl(cis,cis-7-fluoro-4-(4-((trifluoromethyl)thio)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid;

4-(cyclopropyl(cis,cis-7-fluoro-4-(4-((trifluoromethyl)thio)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid; and

4-(cyclopropyl(cis,cis-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)butanoic acid.

15. A pharmaceutical formulation comprising a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

16. A method for treating a disease or condition associated with uncontrolled or inappropriate stimulation of CRTH 2 function, wherein the disease or condition is asthma, allergic rhinitis, or COPD, comprising administering to a patient in need of such treatment a therapeutically amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof.

17. A method for treating a disease or condition associated with uncontrolled or inappropriate stimulation of CRTH 2 function, wherein the disease or condition is asthma, allergic rhinitis, or COPD, comprising administering to a patient in need of such treatment a therapeutically amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof and an additional therapeutic agent.

18. A compound which is 4-{cyclopropyl[cis,cis-4-{[4-(trifluoromethoxy)phenyl]carbonyl}-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl]amino}-4-oxobutanoic acid, or a pharmaceutically acceptable salt thereof.

19. A compound which is 4-[cyclopropyl[cis,cis-7-fluoro-2,3,3a,4,9,9a-hexahydro-4-[4-(trifluoromethoxy)benzoyl]-1H-cyclopenta[b]quinolin-9-yl]amino]-4-oxobutanoic acid, or a pharmaceutically acceptable salt thereof.

20. A compound which is 4-(cyclopropyl((3aS,9R,9aR)-7-fluoro-4-(4-(trifluoromethoxy)benzoyl)-2,3,3a,4,9,9a-hexahydro-1H-cyclopenta[b]quinolin-9-yl)amino)-4-oxobutanoic acid, or a pharmaceutically acceptable salt thereof.

21. A compound which is 4-[cyclopropyl[cis,cis-1,2,2a,3,8,8a-hexahydro-3-[4-(trifluoromethoxy)benzoyl]cyclobuta[b]quinolin-8-yl]amino]-4-oxobutanoic acid, or a pharmaceutically acceptable salt thereof.

22. A compound which is (R)-1-((cis,cis-3-(benzyloxycarbonyl)-5,6-difluoro-1,2,2a,3,8,8a-hexahydrocyclobuta[b]quinolin-8-yl)(cyclopropyl)carbamoyl)azetidine-2-carboxylic acid, or a pharmaceutically acceptable salt thereof.

23. A pharmaceutical formulation comprising a therapeutically effective amount of the compound of claim 18 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

24. A pharmaceutical formulation comprising a therapeutically effective amount of the compound of claim 19 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

25. A pharmaceutical formulation comprising a therapeutically effective amount of the compound of claim 20 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

26. A pharmaceutical formulation comprising a therapeutically effective amount of the compound of claim 21 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

27. A pharmaceutical formulation comprising a therapeutically effective amount of the compound of claim 22 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

28. The pharmaceutical formulation of claim 15 , further comprising a leukotriene receptor antagonist selected from the group consisting of montelukast, zafirlukast, and pranlukast.

29. The pharmaceutical formulation of claim 28 wherein the leukotriene receptor antagonist is montelukast.

30. The method of claim 16 , wherein the disease or condition is asthma.

31. The method of claim 17 , wherein the disease or condition is asthma.

32. The method of claim 17 , wherein the additional therapeutic agent is a leukotriene receptor antagonist selected from the group consisting of montelukast, zafirlukast, and pranlukast.

33. The method of claim 32 , wherein the leukotriene receptor antagonist is montelukast.

34. A method of treating asthma, comprising administering to a patient in need of such treatment a therapeutically amount of a compound of the compound of claim 18 or a pharmaceutically acceptable salt thereof.

35. A method of treating asthma, comprising administering to a patient in need of such treatment a therapeutically amount of a compound of the compound of claim 19 or a pharmaceutically acceptable salt thereof.

36. A method of treating asthma, comprising administering to a patient in need of such treatment a therapeutically amount of a compound of the compound of claim 20 or a pharmaceutically acceptable salt thereof.

37. A method of treating asthma, comprising administering to a patient in need of such treatment a therapeutically amount of a compound of the compound of claim 21 or a pharmaceutically acceptable salt thereof.

38. A method of treating asthma, comprising administering to a patient in need of such treatment a therapeutically amount of a compound of the compound of claim 22 or a pharmaceutically acceptable salt thereof.

39. The method of claim 34 , further comprising administering montelukast to the patient.

40. The method of claim 35 , further comprising administering montelukast to the patient.

41. The method of claim 36 , further comprising administering montelukast to the patient.

42. The method of claim 37 , further comprising administering montelukast to the patient.

43. The method of claim 38 , further comprising administering montelukast to the patient.

44. The pharmaceutical formulation of claim 23 , further comprising montelukast.

45. The pharmaceutical formulation of claim 24 , further comprising montelukast.

46. The pharmaceutical formulation of claim 25 , further comprising montelukast.

47. The pharmaceutical formulation of claim 26 , further comprising montelukast.

48. The pharmaceutical formulation of claim 27 , further comprising montelukast.