N-substituted heterocyclic amines as modulators of chemokine receptor activity

• US 20040067935A1
• Filed: 09/25/2003
• Published: 04/08/2004
• Est. Priority Date: 09/26/2002
• Status: Active Grant

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Batt, Douglas G.
• Granted Patent: US 6,919,356 B2
• Time in Patent Office: Days
• US Class Current: 514/217.12
• CPC Class Codes: A61K 31/40 having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
• CPC Class Codes: A61K 31/41 having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/425 Thiazoles
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: C07D 211/26 with hydrocarbon radicals, substituted by nitrogen atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

The present application describes modulators of chemokine receptors of formula (I):

or pharmaceutically acceptable salt forms thereof, useful for the prevention of asthma and other allergic diseases.

Claims

1. A compound of formula (I):

2. The compound of claim 1, wherein

R^11a and R^12a, at each occurrence are independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CF₂)_rCF₃, (CH₂)_rN(R^18a)R^18b, (CH₂)_rOH, (CH₂)_rOR¹⁹, (CH₂)_rSH, (CH₂)_rSR¹⁹, (CH₂)_rC(O)OH, (CH₂)_rC(O)R¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rN(R^18c)C(O)R¹⁹, (CH₂)_rC(O)OR¹⁹, (CH₂)_rOC(O)R¹⁹, (CH₂)_rS(O)R¹⁹, (CH₂)_rS(O)₂R¹⁹, (CH₂)_rS(O)₂N(R^18a)R^18b, (CH₂)_rN(R^18c)S(O)₂R¹⁹, and (CH₂)_rphenyl substituted with 0-3 R¹⁸;

and

R^11b, R^12b, R^14a and R^14b at each occurrence are independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CF₂)_rCF₃, (CH₂)_qN(R^18a)R^18b, (CH₂)_qOH, (CH₂)_qOR¹⁹, (CH₂)_qSH, (CH₂)_qSR¹⁹, (CH₂)_rC(O)OH, (CH₂)_rC(O)R¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_qN(R^18c)C(O)R¹⁹, (CH₂)_rC(O)OR¹⁹, (CH₂)_qOC(O)R¹⁹, (CH₂)_qS(O)R¹⁹, (CH₂)_qS(O)₂R¹⁹, (CH₂)_qS(O)₂N(R^18a)R^18b, (CH₂)_qN(R^18c)S(O)₂R¹⁹, and (CH₂)_rphenyl substituted with 0-3 R¹⁸.

3. The compound of claim 2, wherein

R¹ and R² are independently selected from H, and C_1-8 alkyl;

R⁴ is absent, taken with the nitrogen to which it is attached to form an N-oxide, or selected from C_1-8 alkyl, (CH₂)_rC_3-6 cycloalkyl, and a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-3 R^4c; and

R^4c, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_3-6 cycloalkyl, Cl, F, Br, I, CN, NO₂, (CF₂)_rCF₃, (CH₂)_rOC_1-5 alkyl, (CH₂)_rOH, (CH₂)_rSC_1-5 alkyl, (CH₂)_rNR^4aR^4a, and (CH₂)_rphenyl.

4. The compound of claim 3, wherein

Z is selected from O and S;

R⁶, at each occurrence, is independently selected from C_1-4 alkyl, (CH₂)_rC_3-6 cycloalkyl, (CH₂)_qNR^6aR^6a, (CH₂)_qOH, (CH₂)_qOR^6b, (CH₂)_rC(O)OH, (CH₂)_rC(O)R^6b, (CH₂)_rC(O) NR^6aR^6a, (CH₂)_qNR^6dC(O)R^6a, (CH₂)_rS(O)₂NR^6aR^6a, (CH₂)_rNR^6dS(O)₂R^6b, and (CH₂)_tphenyl substituted with 0-3 R^6c;

R^6a and R^6a, at each occurrence, are selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, and phenyl;

R^6b, at each occurrence, is independently selected from methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, and phenyl;

R^6c, at each occurrence, is independently selected from C_1-6 alkyl, C_3-6 cycloalkyl, Cl, F, Br, I, CN, NO₂, (CF₂)_rCF₃, (CH₂)_rOC_1-5 alkyl, (CH₂)_rOH, (CH₂)_rSC_1-5 alkyl, and (CH₂)_rNR⁶R⁶d;

R^6d, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, and cyclohexyl;

R⁷, is selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_qOH, (CH₂)_qOR^7d, (CH₂)_qNR^7aR^7a, (CH₂)_rC(O)R^7b, (CH₂)_rC(O)NR^7aR^7a, (CH₂)_qNR^7aC(O)R^7a, (CH₂)_qNR^7aC(O)H, (CH₂)_rC(O)OR^7b, (CH₂)_qOC(O)R^7b, C_1-6 haloalkyl, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-3 R^7c, and a (CH₂)_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R^7c, wherein the heterocyclic system is selected from pyridinyl, thiophenyl, furanyl, indazolyl, benzothiazolyl, benzimidazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indolyl, indolinyl, indazolyl, isoindolyl, isothiadiazolyl, isoxazolyl, piperidinyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl;

R^7a, at each occurrence, is independently selected from H, C_1-6 alkyl, and a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-5 R^7e;

R^7b, at each occurrence, is independently selected from C_1-6 alkyl, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-2 R^7e;

R^7c, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, Cl, Br, I, F, (CF₂)_rCF³, NO₂, CN, (CH₂)_rNR^7fR^7f, (CH₂)_rOH, (CH₂)_rOC_1-4 alkyl, (CH₂)_rSC_1-4 alkyl, (CH₂)_rC(O)OH, (CH₂)_rC(O)R^7b, (CH₂)_rC(O)NR^7fR^7f, (CH₂)_rNR^7fC(O)R^7a, (CH₂)_rC(O)OC_1-4 alkyl, (CH₂)_rOC(O)R^7b, (CH₂)_rC(═

NR^7f)NR^7fR^7f, (CH₂)_rS(O)_pR^7b, (CH₂)_rNHC(═

NR^7f)NR^7fR^7f, (CH₂)_rS(O)₂NR^7fR^7f, (CH₂)_rNR^7fS(O)₂R^7b, and (CH₂)_rphenyl substituted with 0-3 R^7e;

R^7d, at each occurrence, is independently selected from C_1-6 alkyl substituted with 0-3 R^7e, and a C_3-6 carbocyclic residue substituted with 0-3 R^7c;

R^7e, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, C_3-6 cycloalkyl, Cl, F, Br, I, CN, NO₂, (CF₂)_rCF₃, (CH₂)_rOC_1-5 alkyl, OH, SH, (CH₂)_rSC_1-5 alkyl, (CH₂)_rNR^7fR^7f, and (CH₂)_rphenyl;

R^7f, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl and cyclohexyl;

R¹⁰, at each occurrence, is independently selected from H, C_1-4 alkyl, (CH₂)_rC_3-6 cycloalkyl, (CH₂)_rNR^10aR^10a, (CH₂)_rC(O)NR^10aR^10a, (CH₂)_rNR^10dC(O)R^10a, (CH₂)_rS(O)₂NR^10aR^10a, (CH₂)_rNR^10dS(O)₂R^10b, and (CH₂)_tphenyl substituted with 0-3 R^10c;

R^10a and R^10a, at each occurrence, are selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, and phenyl;

R^10b, at each occurrence, is independently selected from methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, and phenyl;

R^10c, at each occurrence, is independently selected from C_1-10 alkyl, C_3-6 cycloalkyl, Cl, F, Br, I, CN, NO₂, (CF₂)_rCF₃, (CH₂)_rOC_1-5 alkyl, (CH₂)_rOH, (CH₂)_rSC_1-5 alkyl, and (CH₂)_rNR^10dR^10d; and

R^10d, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, and cyclohexyl.

5. The compound of claim 4, wherein

R³ is selected from a (CR^3′

H)_r—

C_3-8 carbocyclic residue substituted with 0-5 R¹⁵, wherein the carbocyclic residue is selected from phenyl, naphthyl, and adamantyl; and

a (CR^3′

H)_r-heterocyclic system substituted with 0-3 R¹⁵, wherein the heterocyclic system is selected from pyridinyl, thiophenyl, furanyl, indazolyl, benzothiazolyl, benzimidazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indolyl, indolinyl, indazolyl, isoindolyl, isothiadiazolyl, isoxazolyl, piperidinyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl; and

R^5a is selected from phenyl substituted with 0-5 R¹⁶; and

a heterocyclic residue substituted with 0-3 R¹⁶, wherein the heterocyclic system is selected from pyridinyl, thiophenyl, furanyl, indazolyl, benzothiazolyl, benzimidazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indolyl, indolinyl, isoindolyl, isothiadiazolyl, isoxazolyl, piperidinyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl;

R⁸ is selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CF₂)_rCF₃, (CH₂)_rN(R^18a)R^18b), (CH₂)_rOH, (CH₂) _rOR¹⁹, (CH₂)_rSH, (CH₂)_rSR¹⁹, (CH₂)_rC(O)OH, (CH₂)_rC(O)R¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rN(R^18c)C(O)R¹⁹, (CH₂)_rC(O)OR¹⁹, (CH₂)_rOC(O)R¹⁹, (CH₂)_rS(O)R¹⁹, (CH₂)_rS(O)₂R¹⁹, (CH₂)_rS(O)₂N(R^18a)R^18b, (CH₂)_rN(R^18c)S(O)₂R¹⁹, a (C(R^8a)(R^8b))_r—

C_3-10 carbocyclic residue substituted with 0-5 R¹⁷, and a (C(R^8a)(R^8b))_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R¹⁷ wherein the heterocyclic system is selected from pyridinyl, thiophenyl, furanyl, indazolyl, benzothiazolyl, benzimidazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indolyl, indolinyl, isoindolyl, isothiadiazolyl, isoxazolyl, piperidinyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl;

R^8a and R^8b, at each occurrence, are independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, and (CH₂)_r phenyl substituted with 0-3 R¹⁸;

R⁹ is selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CF₂)_rCF₃, (CH₂)_qN(R^18a)R^18b), (CH₂)_qOH, (CH₂)_qOR¹⁹, (CH₂)_qSH, (CH₂)_qSR¹⁹, (CH₂)_qC(O)OH, (CH₂)_qC(O)R¹⁹, (CH₂)_qC(O)N(R^18a)R^18b, (CH₂)_qN(R^18c)C(O)R¹⁹, (CH₂)_qC(O)OR¹⁹, (CH₂)_qOC(O)R¹⁹, (CH₂)_qS(O)R¹⁹, (CH₂)_qS(O)₂R¹⁹, (CH₂)_qS(O)₂N(R^18a)R^18b, (CH₂)_qN(R^18c)S(O)₂R¹⁹, a (C(R^8a)(R^8b))—

C_3-10 carbocyclic residue substituted with 0-5 R¹⁷, and a (C(R^8a)(R^8b))_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R¹⁷ wherein the heterocyclic system is selected from pyridinyl, thiophenyl, furanyl, indazolyl, benzothiazolyl, benzimidazolyl, benzothiophenyl, benzofuranyl, benzoxazolyl, benzisoxazolyl, quinolinyl, isoquinolinyl, imidazolyl, indolyl, indolinyl, isoindolyl, isothiadiazolyl, isoxazolyl, piperidinyl, pyrrazolyl, 1,2,4-triazolyl, 1,2,3-triazolyl, tetrazolyl, thiadiazolyl, thiazolyl, oxazolyl, pyrazinyl, and pyrimidinyl;

alternatively, R⁸ and R⁹ taken together are selected from ═

O, ═

S, ═

NR^9a;

R^9a is selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CH₂)_rOH, (CH₂)_rOC_1-6 alkyl, (CH₂)_rC(O)R¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rC(O)OR¹⁹, and (CH₂)_rphenyl substituted with 0-3 R¹⁷; and

R^9b, at each occurrence are independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CF₂)_rCF₃, (CH₂)_rN(R^18a)R^18b, (CH₂)_rOH, (CH₂)_rOR¹⁹, (CH₂)_rSH, (CH₂)_rSR¹⁹, (CH₂)_rC(O)OH, (CH₂)_rC(O)R¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rN(R^18c)C(O)R¹⁹, (CH₂)_rC(O)OR¹⁹, (CH₂)_rOC(O)R¹⁹, (CH₂)_rS(O)R¹⁹, (CH₂)_rS(O)₂R¹⁹, (CH₂)_rS(O)₂N(R^18a)R^18b, (CH₂)_rN(R^18c)S(O)₂R¹⁹, and (CH₂)_rphenyl substituted with 0-3 R¹⁷.

6. The compound of claim 5, wherein

R¹ and R² are H;

R^5a is phenyl substituted with 1-3 R¹⁶;

R¹⁶, at each occurrence, is independently selected from C_1-8 alkyl, (CH₂)_rC_3-6 cycloalkyl, CF₃, Cl, Br, I, F, NR^16aR^16a, NO₂, CN, OH, OR^16d, C(O)R^16b, C(O)NR^16aR^16a, and NR^16fC(O)R^16b;

R^16a, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, and (CH₂)_rphenyl substituted with 0-3 R^16e;

R^16b, at each occurrence, is independently selected from methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, and (CH₂)_rphenyl substituted with 0-3 R^16e;

R^16d, at each occurrence, is independently selected from methyl, ethyl, propyl, i-propyl, butyl, and phenyl;

R^16e, at each occurrence, is independently selected from methyl, ethyl, propyl, i-propyl, butyl, Cl, F, Br, I, CN, NO₂, (CF₂)_rCF₃, OH, and (CH₂)_rOC_1-5 alkyl; and

R^16f, at each occurrence, is independently selected from H, methyl, ethyl, propyl, i-propyl, and butyl.

7. The compound of claim 6, wherein the compound is of formula (I-i)

8. The compound of claim 7, wherein

R⁵ is

R^11a and R^12a, at each occurrence are independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, pentyl, hexyl, cyclopropyl, cyclopentyl, cylohexyl, CF₃, (CH₂)_rN(R^18a)R^18b, (CH₂)_rOH;

R^11b, R^12b, R^14a and R^14b at each occurrence are independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, pentyl, hexyl, cyclopropyl, cyclopentyl, cylohexyl, CF₃, (CH₂)_rqN(R^18a)R^18b, (CH₂)_rqOH;

R²⁵ at each occurrence is independently selected from H, methyl, ethyl, propyl, i-propyl, butyl, cyclopropyl, cyclopentyl, cyclohexyl, (CH₂)_rC(O)R¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rC(O)OR¹⁹, and (CH₂)_rphenyl substituted with 0-3 R¹⁷.

9. The compound of claim 8, wherein

R⁵ is

R⁷, at each occurrence, is selected from H, methyl, ethyl, propyl, i-propyl, butyl, (CH₂)_qOH;

R^11a and R^12a, at each occurrence, are independently selected from H, methyl, and ethyl;

R^11b, R^12b, R^14a, and R^14b, at each occurrence, are independently selected from H, methyl, ethyl and OH; and

R16, at each occurrence, is independently selected from methyl, Cl, F, CF₃, and CN.

10. The compound of claim 7, wherein

R⁵ is

11. The compound of claim 9, wherein R⁸ and R⁹ do not both equal H.

12. The compound of claim 1, wherein the compound is selected from the compounds of Table 1 or

1-{1-[3-(4-fluorophenyl)-2,2-dimethylpropyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea;

1-{1-[3-(4-fluorophenyl)-propyl]-piperidin-3-ylmethyl}-3-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea;

1-[3-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-trifluoromethylphenyl)-ethyl]-piperidin-3-ylmethyl}-urea;

1-(5-acetyl-4-methylthiazol-2-yl)-3-{1-[2-(4-fluorophenyl)ethyl]-piperidin-3-ylmethyl}urea;

1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-3-{trans-1-[2-(4-fluorophenyl)-ethyl]-4-methylpiperidin-3-ylmethyl}-urea;

1-[3-(1-methyl-1H-tetrazol-5-yl)phenyl]-3-{cis-1-[2-(4-fluorophenyl)-ethyl]-4-methylpiperidin-3-ylmethyl}-urea;

trans-1-{4-(benzyl-methylamino)-1-[2-(4-fluorophenyl)-ethyl]-piperidin-3-ylmethyl}-3-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea;

trans-1-{4-methylamino-1-[2-(4-fluorophenyl)-ethyl]-piperidin-3-ylmethyl}-3-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea;

trans-N-{3-{3-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-ureidomethyl}-1-[3-(4-fluoro-phenyl)-propyl]-piperidin-4-yl}-N-methyl-acetamide;

trans-N-{3-{3-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-ureidomethyl}-1-[3-(4-fluoro-phenyl)-propyl]-piperidin-4-yl}-N-methyl-methanesulfonamide;

(S)-1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-fluorophenyl) -2-oxo-ethyl]-piperidin-3-ylmethyl}-urea;

(S)-1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-fluorophenyl) -2-hydroxyimino-ethyl]-piperidin-3-ylmethyl}-urea;

1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-fluorophenyl)-2-(RS)-hydroxyethyl]-(S)-piperidin-3-ylmethyl}-urea;

(S)-1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-3-{1-[2-(4-fluorophenyl) -ethyl]-piperidin-3-ylmethyl}-urea;

1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-3-{1-[2-(4-fluorophenyl) -ethyl]-4-ethylpiperidin-3-ylmethyl}-urea; and

1-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)phenyl]-3-{1-[2-(4-fluorophenyl) -ethyl]-4,4-dimethylpiperidin-3-ylmethyl}-urea.

13. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 1.

14. 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.

15. A method for treating asthma, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1.

16. 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.

17. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 16, or a pharmaceutically acceptable salt thereof.

18. The method of claim 17 wherein modulation of chemokine receptor activity comprises contacting a CCR3 receptor with an effective inhibitory amount of the compound.

19. A method for treating inflammatory disorders comprising administering to a patient in need thereof a to claim 1, or a pharmaceutically acceptable salt thereof.

20. A method according to claim 19, 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.

21. The method according to claim 20, wherein the disorder is selected from asthma, allergic rhinitis, atopic dermatitis, and inflammatory bowel diseases.

22. The method according to claim 21, wherein the disorder is asthma.