Claims
- 1. A compound of formula (I):
- 2. The compound of claim 1, wherein:
R1 is selected from C1-6 alkyl, a (CH2)r-carbocyclic residue substituted with 0-5 R5, wherein the carbocyclic residue is selected from phenyl, C3-6 cycloalkyl, naphthyl, and adamantyl; and a (CH2)r-heterocyclic system substituted with 0-3 R5, wherein the heterocyclic system is selected from pyridinyl, thiophenyl, furanyl, indazolyl, benzo[1,3]dioxolyl benzothiazolyl, benzimidazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolyl, isothiadiazolyl, isoxazolyl, 4-oxo-4,5-dihydro-thiazol-2-yl, piperidinyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl.
- 3. The compound of claim 2, wherein:
R2, at each occurrence, is selected from NR4aR4a, NR4fC(O)R4b, and NR4fS(O)2R4b; R4a, at each occurrence, are selected from H, C1-6 alkyl, C3-6 cycloalkyl, and (CH2)rphenyl substituted with 0-3 R4e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R4e; alternatively, two R4a join to form a 5, 6, or 7-membered ring containing from 0-1 additional heteroatoms selected from N and O, wherein the ring is selected from pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl, the ring containing 0-1 C═O and being subsituted with 0-1 Rf; R4b, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and (CH2)rphenyl substituted with 0-3 R4e; R4e, at each occurrence, is selected from C1-6 alkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, OH, and (CH2)rOC1-5 alkyl; R4f, at each occurrence, is selected from H, C3-6 cycloalkyl, and C1-5 alkyl; alternatively, R4b and R4f join to form a 5, 6, or 7-membered ring, wherein the ring is selected from 2-piperidinone, the ring being subsituted with 0-1 Rf; Rf, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, pentyl, hexyl, cyclopropyl, cyclopentyl, cyclohexyl, and phenyl; and r is selected from 0, 1, and 2.
- 4. The compound of claim 3, wherein:
R1 is selected from C1-6 alkyl selected from methyl, ethyl, propyl, i-propyl, and butyl, a C3-10 carbocyclic residue substituted with 0-3 R5, wherein the carbocyclic residue is selected from cyclopropyl, cyclopentyl, cyclohexyl, phenyl, naphthyl and adamantyl, and a (CH2)r-heterocyclic system substituted with 0-3 R5, wherein the heterocyclic system is selected from pyridinyl, thiophenyl, furanyl, indazolyl, benzo[1,3]dioxolyl, benzothiazolyl, benzimidazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indazolyl, indolyl, indolinyl, isoindolyl, isothiadiazolyl, isoxazolyl, 4-oxo-4,5-dihydro-thiazol-2-yl, piperidinyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl; and R5, at each occurrence, is selected from C1-8 alkyl, (CH2)rC3-6 cycloalkyl, CF3, Cl, Br, I, F, (CH2)rNR5aR5a, NO2, CN, OH, (CHR′)rOR5d, (CH2)rC(O)R5b, (CH2)rC(O)OR5d, (CH2)rC(O)NR5aR5a, (CH2)rNR5fC(O)R5b, (CH2)rS(O)pR5b, (CH2)rS(O)2NR5aR5a, (CH2)rNR5fS(O)2R5b, (CH2)rphenyl substituted with 0-3 R5e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R5e; R5a, at each occurrence, are selected from H, C1-6 alkyl, C3-6 cycloalkyl, and (CH2)rphenyl substituted with 0-3 R5e; R5b, at each occurrence, is selected from H, C1-6 alkyl, C3-6 cycloalkyl, and (CH2)rphenyl substituted with 0-3 R5e; R5d, at each occurrence, is selected from C1-6 alkyl and phenyl; R5e, at each occurrence, is selected from C1-6 alkyl, Cl, F, Br, I, CN, NO2, (CF2)rCF3, OH, and (CH2)rOC1-5 alkyl; and R5f, at each occurrence, is selected from H, and C1-5 alkyl.
- 5. The compound of claim 4, wherein:
R1 is selected from C1-6 alkyl selected from methyl, ethyl, propyl, i-propyl, and butyl, a C3-10 carbocyclic residue substituted with 0-2 R5, wherein the carbocyclic residue is selected from cyclopropyl, cyclopentyl, cyclohexyl, phenyl and adamantyl, and a heterocyclic system substituted with 0-3 R5, wherein the heterocyclic system is selected from pyridinyl, indazolyl, benzo[1,3]dioxolyl, benzothiazolyl, benzoxazolyl, benzisoxazolyl, 2,3-dihydroindolyl, indolyl, indazolyl, indolinyl, isoxazolyl, 4-oxo-4,5-dihydro-thiazol-2-yl,pyrrazolyl, pyrimidinyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, and oxazolyl; and R5, at each occurrence, is selected from methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, CF3, Cl, Br, I, F, CN, OH, (CHR′)rOR5d, C(O)R5b, C(O)OR5d, C(O)NR5aR5a, (CH2)rS(O)pR5b, (CH2)rNR5fS(O)2R5b, (CH2)rphenyl substituted with 0-3 R5e, and a (CH2)r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R5e, wherein the heterocyclic system is selected from tetrazolyl, imidazolyl, pyrimidinyl, pyrrolidinyl, and isoxazolyl; R5a, at each occurrence, are selected from H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, and hexyl; R5b, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, and hexyl; R5d, at each occurrence, is selected from methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, and hexyl; and R5e, at each occurrence, is selected from methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, and hexyl.
- 6. The compound of claim 5, wherein:
R2, at each occurrence, is selected from NR4aR4a, NR4fC(O)R4b, and NR4fS(O)2R4b; R4a, at each occurrence, are selected from H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl; alternatively, two R4a join to form a 5, 6, or 7-membered ring containing from 0-1 additional heteroatoms selected from N and O, wherein the ring is selected from pyrrolidinyl, piperidinyl, morpholinyl and piperazinyl, the ring being subsituted with 0-1 Rf; R4b, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, and hexyl; R4f, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, s-butyl, i-butyl, t-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; alternatively, R4b and R4f join to form a 5, 6, or 7-membered ring, wherein the ring is selected from 2-piperidinone, the ring being subsituted with 0-1 Rf; and Rf, at each occurrence, is selected from H, methyl, ethyl, propyl, and i-propyl.
- 7. The compound of claim 1, wherein the compound is selected from compounds of Table 1 and Table 2.
- 8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.
- 9. A method for modulation of chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1.
- 10. A method for treating asthma, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1.
- 11. The method of claim 10 wherein modulation of chemokine receptor activity comprises contacting a CCR3 receptor with an effective inhibitory amount of the compound.
- 12. A method for treating inflammatory disorders comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof.
- 13. A method of treating disorders comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the disorder is selected from asthma, allergic rhinitis, atopic dermatitis, inflammatory bowel diseases, idiopathic pulmonary fibrosis, bullous pemphigoid, helminthic parasitic infections, allergic colitis, eczema, conjunctivitis, transplantation, familial eosinophilia, eosinophilic cellulitis, eosinophilic pneumonias, eosinophilic fasciitis, eosinophilic gastroenteritis, drug induced eosinophilia, HIV infection, cystic fibrosis, Churg-Strauss syndrome, lymphoma, Hodgkin's disease, and colonic carcinoma.
- 14. The method according to claim 13, wherein the disorder is selected from asthma, allergic rhinitis, atopic dermatitis, and inflammatory bowel diseases.
- 15. The method according to claim 14, wherein the disorder is asthma.
- 16. A method of inhibiting chemokine receptor activity comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1.
- 17. The method of claim 16, wherein inhibiting chemokine receptor activity comprises inhibiting CCR-1 activity.
- 18. A method of treating disorders comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, wherein the disorder is selected from rheumatoid arthritis, transplantation, and multiple sclerosis.
- 19. A compound of Formula (V)
- 20. The compound of claim 19, wherein Pg is benzyloxycarbonyl (Cbz).
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the priority benefit of U.S. Provisional Application No. 60/478,022, filed Jun. 12, 2003, the disclosure of which is incorporated herein by reference in its entirety.
Provisional Applications (1)
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Number |
Date |
Country |
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60478022 |
Jun 2003 |
US |