Claims
- 1. A compound of Formula I
- 2. The compound of claim 1 wherein d is 1.
- 3. The compound of claim 1 wherein R3 is H.
- 4. The compound of claim 1 wherein X is O or S.
- 5. The compound of claim 1 wherein Ar is phenyl, naphthyl, pyridyl, carbazolyl, indolinyl, dibenzylfuryl, benzothiazolyl, or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected form O, S, and N optionally fused to phenyl.
- 6. The compound of claim 1 wherein Y is halo, phenyl optionally fused to another phenyl ring or to a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O; or
a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S and O, optionally fused to a phenyl ring, each cyclic moiety being optionally substituted with one or more substituents independently selected from COR2; halo; OR1; R1; C1-C10COR2; tetrazolo; phenyl optionally substituted with halo, C1-C4 alkyl, or C1C4 alkoxy.
- 7. The compound of claim 1 wherein
R is hydroxy, halo, cyano, C1-C10 alkyl optionally substituted with phenyl, C1-C10haloalkyl, CF3, NR1R1, SR1, OR1, SO2R2, OCOR2, NR1COR2, COR2, NR1SO2R2, phenyl, or a 5- or 6-membered heterocycle with from 1 to 2 heteroatoms selected independently from O, S, and N, each cyclic moiety being optionally substituted with hydroxy, R1, halo, cyano, NR1R1, SR1, CF3, OR1, C3-C8 cycloalkyl, NR1COR2, COR2, SO2R2, OCOR2, NR1SO2R2, C1-C10 alkyl, or C1-C10 alkoxy; R1 is hydrogen, C1-C10 alkyl optionally substituted with 1 to 4 substituents each independently selected from hydroxy, halo, phenyl optionally substituted with CO2C1-C4 alkyl or CO2H, S(O)bC1-C10 alkyl, and C1-C10 alkoxy, or C3-C8 cycloalkyl, cycloalkyl, phenyl or naphthyl, each optionally substituted with 1 to 4 substituents each independently selected from halo, nitro, oxo, C1-C10 alkyl, C1-C10alkoxy, and C1-C10 alkylthio; R1 is R1; OR1; NR1R1; NHS(O)bphenyl optionally substituted with halo, C1-C4 alkyl, C1-C4 alkoxy, halo or nitro; NHS(O)bnaphthyl; NHS(O)bC1-C10 alkyl; or a 5- or 6-membered heterocycle with one or two heteroatoms selected independently from O, S, and N, said heterocyclic moiety being optionally substituted with R1; R3 is hydrogen, or benzyl; R4 is hydrogen, C1-C10 alkyl, C1-C10 alkyl-phenyl, C1-C10 alkyl-pyridine; R5 is hydrogen or COOH; Ar is phenyl optionally fused to a cyclohexyl, phenyl or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from O, S, and N, said bicyclic moiety being optionally fused to phenyl, or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, optionally fused to phenyl; X is O or S; Y is halo, R1, OR1SR1, CO2R1, NR1R1, S(O)b-phenyl-CO2R1 or phenyl optionally fused to another phenyl ring or to a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, optionally fused to a phenyl ring, each cyclic moiety being optionally substituted with one or more substituents independently selected from COR2; halo; OR1; R1; C1-C10COR2; phenyl optionally substituted with halo, C1-C4 alkyl, or C1C4alkoxy; tetrazolo; or 573 where, when the two R4 groups attached to the same C are both alkyl, they optionally may be joined so that, when taken together with the C to which they are attached, they form a spiro ring of 3, 5, or 6 C atoms, or where the R4attached to N and one R4 attached to the adjacent C are both alkyl, they optionally may be joined so that, taken together with the atoms to which they are attached, they form a 5- or 6-membered heterocycle; a is 0, 1, or 2; b is 0, 1 or 2 d is 1 and e is 1; and the pharmaceutically acceptable salts and esters thereof.
- 8. The compound of claim 1 wherein,
R is hydroxy, halo, cyano, C1-C4 alkyl, C1-C4 haloalkyl, CF3, NR1R1, SR1, OR1, SO2R2, OCOR2, NR1COR2, COR2, NR1SO2R2, phenyl, or a 5- or 6-membered heterocycle with from 1 to 2 heteroatoms selected independently from O, S, and N, each cyclic moiety being optionally substituted with hydroxy, R1, halo, cyano, NR1R1, SR1, CF3, OR1, C3-C8 cycloalkyl, NR1COR2, COR2, SO2R2, OCOR2, NR1SO2R2, C1-C10 alkyl, or C1-C4 alkoxy; R1 is hydrogen, C1-C4 alkyl optionally substituted with 1 to 4 substituents each independently selected from hydroxy, halo, phenyl optionally substituted with CO2C1-C4 alkyl or CO2H, CO2C1-C4 alkyl, CO2H, S(O)bC1-C4 alkyl, and C1-C4 alkoxy, or C3-C6 cycloalkyl, phenyl or naphthyl, each optionally substituted with 1 to 2 substituents each independently selected from halo, nitro, C1-C4 alkyl, C1-C4 alkoxy, and C1-C4 alkylthio; R1 is R1; OR1; NR1R1; NHS(O)bphenyl optionally substituted with halo, C1-C4 alkyl, C1C4 alkoxy, halo or nitro; NHS(O)bnaphthyl; NHS(O)bC1-C10 alkyl; or a 5- or 6-membered heterocycle with one or two heteroatoms selected independently from O, S, and N, said heterocyclic moiety being optionally substituted with R1; R3 is hydrogen, or benzyl; R4 is hydrogen, C1-C10 alkyl, C1-C10 alkyl-phenyl, C1-C10 alkyl-pyridine; R5 is hydrogen or COOH; Ar is phenyl optionally fused to a cyclohexyl, phenyl or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from O, S, and N, said bicyclic moiety being optionally fused to phenyl, or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, optionally fused to phenyl; X is O or S; Y is halo, R1, OR1SR1, CO2R1, NR1R1, S(O)b-phenyl-CO2R1 or phenyl optionally fused to another phenyl ring or to a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S and O, or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, optionally fused to a phenyl ring, each cyclic moiety being optionally substituted with one or more substituents independently selected from COR2, halo, OR1, R1, C1-C10COR2, tetrazolo, phenyl optionally substituted with halo, C1-C4 alkyl, or C1C4 alkoxy; a is 0, 1, or 2 b is 0, 1 or 2 d is 1 and e is 1; and the pharmaceutically acceptable salts and esters thereof.
- 9. The compound of claim 1 wherein,
R is halo, C1-C4 alkyl, C1-C4 haloalkyl, CF3; R1 is hydrogen, C1-C4 alkyl optionally substituted with 1 to 4 substituents each independently selected from hydroxy, halo, phenyl, or C3-C6 cycloalkyl, phenyl or naphthyl, each optionally substituted with 1 to 2 substituents each independently selected from halo, C1-C4 alkyl, C1-C4alkoxy, and C1-C4 alkylthio; R2 is R1; OR1; NR1R1; NHS(O)bphenyl optionally substituted with halo, C1-C4 alkyl, C1-C4 alkoxy; NHS(O)bnaphthyl; NHS(O)bC1-C10 alkyl; or a 5- or 6-membered heterocycle with one or two heteroatoms selected independently from O, S, and N, said heterocyclic moiety being optionally substituted with R1; R3 is hydrogen, R4 is hydrogen, C1-C10 alkyl, C1-C10 alkyl-phenyl, C1-C10 alkyl-pyridine; R5 is hydrogen or COOH; Ar is phenyl optionally fused to a cyclohexyl, phenyl or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from O, S, and N, said bicyclic moiety being optionally fused to phenyl, or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, optionally fused to phenyl; X is O; Y is halo, R1, S(O)b-phenyl-CO2R1 or phenyl optionally fused to another phenyl ring or to a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, or a 5- or 6-membered heterocycle containing one or more heteroatoms each independently selected from N, S, and O, optionally fused to a phenyl ring, each cyclic moiety being optionally substituted with one or more substituents independently selected from COR2, halo, OR1, R1, C1-C4COR2, tetrazolo, phenyl optionally substituted with halo, C1-C4 alkyl, or C1C4 alkoxy; a is 0, 1, or 2 b is 0, 1 or 2 d is 1 and e is 1; and the pharmaceutically acceptable salts and esters thereof.
- 10. The compound of claim 1 selected from the group consisting of
(2S)-1-({[(2R)-6-iodo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)-3-phenoxy-2-propanol; (2S)-1-(Benzyl{[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)-3-phenoxy-2-propanol; (2S)-1-(Benzyl{[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)-3-phenoxy-2-propanol hyrdrobromide; Methyl 4-[(2R)-2-({benzyl[2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate; Methyl 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate; Methyl 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate methanesulfonate N-{3-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoyl}benzenesulfonamide; Methyl 6-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-naphthoate; Methyl 6-{(2R)-2-[({(2S)-2-hydroxy-3-[2-(trifluoromethyl)phenoxy]propyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}-2-naphthoate; Methyl 6-[(2R)-2-({[(2S)-2-hydroxy-3-(3-pyridinyloxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-naphthoate; Methyl 6-[(2R)-2-({[(2S)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-naphthoate; Methyl 6-[(2R)-2-({[(2S)-2-hydroxy-3-(2-hydroxyphenoxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-naphthoate; Ethyl 7-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-naphthoate; Methyl 5-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2,3-dihydro-1-benzofuran-7-carboxylate; Ethyl 4-[(2S)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-1,5-dimethyl-1H-pyrazole-3-carboxylate; Methyl 5-[(2S)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-3-thiophenecarboxylate; Methyl 4-[(2S)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-thiophenecarboxylate; Methyl 2-[(2S)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-5-phenyl-1,3-thiazole-4-carboxylate; 4-{(2R)-2-[({(2S)-2-hydroxy-3-[4-(2-methoxyethyl)phenoxy]propyl}amino)methyl]-3,4-dihydro-2H-chromen-6-yl}benzoic acid; 4-[(2R)-2-({[(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-Hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-3-(2-ethylphenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(3-isopropylphenoxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-3-(2-ethoxyphenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(2-isopropoxyphenoxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-3-(2-chlorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-{(2R)-2-[({(2S)-2-hydroxy-3-[2-(trifluoromethyl)phenoxy]propyl}amino)methyl]-3,4 -dihydro-2H-chromen-6-yl}benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(3-pyridinyloxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-3-(4-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-3-(2-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(2-hydroxyphenoxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 3-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 3-[(2R)-2-({[(2S)-3-(4-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 3-[(2R)-2-({[(2S)-3-(2-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(phenylsulfanyl)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(2-isopropylphenylsulfanyl)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-(2-fluorophenylsulfanyl)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 6-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-naphthoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-thiophenecarboxylic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-1,5-dimethyl-1H-pyrazole-3-carboxylic acid; 5-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2,3-dihydro-1-benzofuran-7-carboxylic acid; 5-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-3-thiophenecarboxylic acid; 2-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-5-phenyl-1,3-oxazole-4-carboxylic acid; 2-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-5-phenyl-1,3-thiazole-4-carboxylic acid; 2-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-4-phenyl-1,3-thiazole-5-carboxylic acid; 2-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-4-isopropyl-1,3-thiazole-5-carboxylic acid; 2-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-5-isopropyl-1,3-thiazole-4-carboxylic acid; 2-(butylamino)-4-[(2R)-2-({[(2)-2-hydroxy-3-(phenyloxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-[(2-methoxyethyl)amino]benzoic acid; 2-(cyclohexylamino)-4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 2-amino-4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 2-(diethylamino)-4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-(isobutylamino)benzoic acid; 2-(cyclobutylamino)-4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-(1-piperidinyl)benzoic acid; 4-[(2S)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-methoxybenzoic acid; 2-ethoxy-4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 2-propoxy-4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-isobutoxybenzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-(2-methoxyethoxy)benzoic acid; 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-2-isopropoxybenzoic acid; 2-butoxy-4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 2-hydroxy-4-[(2S)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid; 5-[(2S)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-1,1′-biphenyl-2-carboxylic acid; 4′-chloro-5-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-1,1′-biphenyl-2-carboxylic acid; 4′-methyl-5-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-1,1′-biphenyl-2-carboxylic acid; 4′-tert-butyl-5-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]-1,1′-biphenyl-2-carboxylic acid; 4-[(2R)-2-({[2-hydroxy-3-(2-methylphenoxy)propyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid trifluoroacetate; 4-[(2R)-2-({[3-(4-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid trifluoroacetate; 4-[(2R)-2-({[3-(2-chlorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid trifluoroacetate; 4-[(2R)-2-({[3-(1,1′-biphenyl-2-yloxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid trifluoroacetate; 4-[(2R)-2-({[(2S)-3-(2-chlorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid trifluoroacetate; 4-[(2R)-2-({[(2S)-3-(2-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid trifluoroacetate; 4-[(2R)-2-({[(2S)-3-(3-chlorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoic acid trifluoroacetate; 3-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]propanoic acid; 3-[(2R)-2-({[(2S)-3-(2-chlorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]propanoic acid; 3-[(2R)-2-({[(2S)-3-(2-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]propanoic acid; and 3-[(2R)-2-({[(2S)-3-(4-fluorophenoxy)-2-hydroxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]propanoic acid trifluoroacetate.
- 11. A compound which is N-Benzyl-N-{[(2R)-6-bromo-3,4-dihydro-2H-chromen -2-yl]methyl}amine;
- 12. A method of preparing the compound of claim 1, comprising the step of using a compound of Formula 2 as an intermediate,
- 13. A method of preparing the compound of claim 1, comprising the step of using as an intermediate a compound selected from the group consisting of
N-Benzyl-N-{[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methyl}amine (2S)-1-(Benzyl{[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)-3-phenoxy-2-propanol; (2S)-1-(Benzyl{[(2R)-6-bromo-3,4-dihydro-2H-chromen-2-yl]methyl}amino)-3-phenoxy-2-propanol hydrobromide; Methyl 4-[(2R)-2-({benzyl[2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate; Methyl 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate; and Methyl 4-[(2R)-2-({[(2S)-2-hydroxy-3-phenoxypropyl]amino}methyl)-3,4-dihydro-2H-chromen-6-yl]benzoate methanesulfonate.
- 14. A method of preparing the compound of Formula I comprising the reaction of a compound of Formula 2
- 15. A pharmaceutical composition comprising an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt and esters thereof in combination with a pharmaceutically acceptable carrier.
- 16. A pharmaceutical composition for the treatment of diabetes, impaired fasting glucose, impaired glucose tolerance, obesity, hypertriglyceridaemia, hypercholesterolaemia, lowering high-density lipoprotein levels, atherosclerosis, cardiovascular diseases and related diseases, gastrointestinal disorders, neurogenetic inflammation, ocular hypertension, glaucoma, urological disorders, benign prostatic hyperplasia, and incontinence, comprising an effective amount of a compound of claim 1 or a pharmaceutically acceptable salt and ester thereof in combination with a pharmaceutically acceptable carrier.
- 17. A composition comprising an effective amount of a compound of claim 1 or a salt and esters thereof in combination with an inert carrier.
- 18. A method of treating a beta-3 adrenergic receptor-mediated condition which comprises administering to a subject in need thereof a pharmaceutically effective amount of a compound of Formula I, or a salt and ester thereof.
- 19. A method of treating diabetes, impaired fasting glucose, and impaired glucose tolerance which comprises administering to a subject in need thereof a pharmaceutically effective amount of a compound of Formula I, or a salt and ester thereof.
- 20. A method of treating obesity which comprises administering to a subject in need thereof a pharmaceutically effective amount of a compound of Formula I, or a salt and ester thereof.
- 21. A method of treating benign prostatic hyperplasia which comprises administering to a subject in need thereof a pharmaceutically effective amount of a compound of Formula I, or a salt and ester thereof.
- 22. A method of treating hypertriglyceridaemia, hypercholesterolaemia, lowering high-density lipoprotein levels, atherosclerosis, cardiovascular diseases and related diseases which comprises administering to a subject in need thereof a pharmaceutically effective amount of a compound of Formula I, or a salt and ester thereof.
Parent Case Info
[0001] This application claims benefit of U.S. Provisional Application Ser. No. 60/254,735, filed Dec. 11, 2000, the contents of which are incorporated herein by reference in their entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60254735 |
Dec 2000 |
US |