N-substituted heterocyclic amines as modulators of chemokine receptor activity

• US 6,919,356 B2
• Filed: 09/25/2003
• Issued: 07/19/2005
• Est. Priority Date: 09/26/2002
• Status: Expired due to Term

• Current Assignee: Bristol-Myers Squibb Company
• Original Assignee: Bristol-Myers Squibb Company
• Inventors: Batt, Douglas G.
• Primary Examiner(s): AULAKH, CHARANJIT
• Application Number:
  US10/670,596
• Publication Number:
  US 20040067935A1
• Time in Patent Office: 663 Days
• Field of Search: 514/326, 514/331, 546/210, 546/209, 546/231
• US Class Current: 514/326
• 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):

or stereoisomers or pharmaceutically acceptable salts thereof, wherein;

Z is selected from O, S, N(R^d), C(CN)₂, CH(NO₂), and CH(CN);

X is C(R⁸)(R⁹);

R¹ and R² are independently selected from H, C_1-8 alkyl, C_2-8 alkenyl, and C_2-8 alkynyl;

R^d is selected from H, C₁-C₆ alkyl, C₃-C₆ cycloalkyl, CON(R^f)R^f, OR^e, CN, NO₂, and (CH₂)_r-phenyl substituted with 0-3 R¹⁸;

R^e, at each occurrence, is independently selected from H, C_1-6 alkyl, C_3-6 cycloalkyl, and phenyl substituted with 0-3 R¹⁸;

R^f, at each occurrence, is independently selected from H, C_1-6 alkyl, C_3-6 cycloaklyl, and phenyl substituted with 0-3 R¹⁸, or optionally, two R^f may be taken together with the nitrogen to which both are attached to form a pyrrolidine, piperidine, piperazine or morpholine ring;

R³ is selected from a (CR³′

R³′

)_r—

C_3-6 carbocyclic residue substituted with 0-5 R¹⁵;

R³′

, at each occurrence, is independently selected from H, C_1-6 alkyl, (CH₂)_rC_3-6 cycloalkyl, and phenyl;

R⁴ is absent, taken with the nitrogen to which it is attached to form an N-oxide, or selected from C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CH₂)_qC(O)R^4b, (CH₂)_qC(O)NR^4aR^4a, (CH₂)_qC(O)OR^4b, and a (CH₂)_r—

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

R^4a, at each occurrence, is independently selected from H, C_1-6 alkyl, (CH₂)_rC_3-6 cycloalkyl, and phenyl;

R^4b, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, (CH₂)_rC_3-6 cycloalkyl, C_2-8 alkynyl, and phenyl;

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;

R⁵ is selected from

Y is selected from O, N(R²⁵), S, S(O) and S(O)₂;

ring B is a 5-7 membered cycloalkyl ring optionally

containing a C═

O, and being substituted with 0-2 R^11a, wherein the cycloalkyl is fused with a benzo group substituted with 0-3 R¹⁶ or is fused with a 5-6 membered aromatic heterocyclic ring having 0-3 N, 0-1 O, or 0-1 S, the heterocyclic ring being substituted with 0-3 R¹⁶;

alternatively, ring B is a fused 5-7 membered saturated heterocyclic ring containing 0-1 O, N(R¹⁶), S, S(O), and S(O)₂, substituted with 0-2 R^11a, the heterocyclic ring being fused with a benzo group substituted with 0-3 R¹⁶ or is fused with a 5-6 membered heterocyclic ring having 0-3 N, 0-1 O, or 0-1 S, the heterocyclic ring being substituted with 0-3 R¹⁶;

provided that if ring B is a heterocyclic ring, then the number of carbon atoms separating the heteroatom of ring B and the nitrogen atom of structure (I) bonded to R⁵ is at least 2;

R^5a is selected from a C_3-10 carbocyclic residue substituted with 0-5 R¹⁶, and a 5-10 membered heterocyclic residue containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R¹⁶;

R⁶, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CF₂)_rCF³, CN, (CH₂)_rNR^6aR^6a, (CH₂)_qOH, (CH₂)_qOR^6b, (CH₂)_qSH, (CH₂)_qSR^6b, (CH₂)_rC(O)OH, (CH₂)_rC(O)R^6b, (CH₂)_rC(O)NR^6aR^6a, (CH₂)_qNR^6dC(O)R^6a, (CH₂)_rC(O)OR^6b, (CH₂)_qOC(O)R^6b, (CH₂)_rS(O)_pR^6b, (CH₂)_rS(O)₂NR^6aR^6a, (CH₂)_rNR^6dS(O)₂R^6b, and (CH₂)_tphenyl substituted with 0-3 R^6c;

R^6a, at each occurrence, is independently selected from H, C_1-6 alkyl, C_3-6 cycloalkyl, and phenyl substituted with 0-3 R^6c;

R_6b, at each occurrence, is independently selected from C_1-6 alkyl, C_3-6 cycloalkyl, and phenyl substituted with 0-3 R^6c;

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)_rNR^6dR^6d;

R_6d, at each occurrence, is independently selected from H, C₁₆ alkyl, and C_3-6 cycloalkyl;

R⁷, at each occurrence, is independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_qOH, (CH₂)_qSH, (CH₂)_qOR^7d, (CH₂)_qSR^7d, (CH₂)_qNR^7aR^7a, (CH₂)_rC(O)OH, (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, (CH₂)_qS(O)_pR^7b, (CH₂)_qS(O)₂NR^7aR^7a, (CH₂)_qNR^7aS(O)₂R^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;

R^7a, at each occurrence, is independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-5 R^7e, and a (CH₂)_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R^7e;

R^7b, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-2 R^7e, and a (CH₂)_r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 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, alkenyl, alkynyl, 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, C_1-6 alkyl, and C_3-6 cycloalkyl;

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;

R^8a and R^8b, at each occurrence, are independently selected from H, C_1-6 alkyl, (CH₂)_rC_3-6 cycloalkyl, and (CH₂)_rphenyl 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))_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;

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, (CH₂)_rS(O)₂R¹⁹, (CH₂)_rS(O)₂N(R^18a)R^18b, and (CH₂)_rphenyl substituted with 0-3 R¹⁷;

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;

R¹⁰, at each occurrence, is independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CF₂)_rCF³, CN, (CH₂)_rNR^10aR^10a, (CH₂)_rOH, (CH₂)_rOR^10b, (CH₂)_rSH, (CH₂)_rSR^10b, (CH₂)_rC(O)OH, (CH₂)_rC(O)R^10b, (CH₂)_rC(O)NR^10aR^10a, (CH₂)_rNR^10dC(O)R^10a, (CH₂)_rC(O)OR^10b, (CH₂)_rOC(O)R^10b, (CH₂)_rS(O)_pR^10b, (CH₂)_rS(O)₂NR^10aR^10a, (CH₂)_rNR^10dS(O)₂R^10b, and (CH₂)_tphenyl substituted with 0-3 R^10c;

R^10a, at each occurrence, is independently selected from H, C_1-6 alkyl, C_3-6 cycloalkyl, and phenyl substituted with 0-3 R^10c;

R^10b, at each occurrence, is independently selected from C_1-6 alkyl, C_3-6 cycloalkyl, and phenyl substituted with 0-3 R^10c;

R^10c, 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)_rNR^10dR^10d;

R^10d, at each occurrence, is independently selected from H, C_1-6 alkyl, and C_3-10 cycloalkyl;

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;

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;

alternatively, R^11a and R^11b taken together are selected from ═

O, or ═

NOH, or alternatively, R^12a and R^12b taken together are selected from ═

O, or ═

NOH;

R¹⁵, at each occurrence, is independently selected from C_1-8 alkyl, (CH₂)_rC_3-6 cycloalkyl, Cl, Br, I, F, NO₂, CN, (CHR′

)_rNR^15aR^15a, (CHR′

)_rOH, (CHR′

)_rO(CHR′

)_rR^15d, (CHR′

)_rSH, (CHR′

)_rC(O)H, (CHR′

)_rS(CHR′

)_rR^15d, (CHR′

)_rC(O)OH, (CHR′

)_rC(O)(CHR′

)_rR^15b, (CHR′

)_rC(O)NR^15aR^15a, (CHR′

)_rNR^15fC(O)(CHR )_rR^15b, (CHR′

)_rNR^15fC(O)NR^15fR^15f, (CHR′

)_rC(O)O(CHR′

)_rR^15d, (CHR′

)_rOC(O)(CHR′

)_rR^15b, (CHR′

)_rC(═

NR^15f)NR^15aR^15a, (CHR′

)_rNHC(═

NR^15f)NR^15fR^15f, (CHR′

)_rS(O)_p(CHR′

)_rR^15b, (CHR′

)_rS(O)₂NR^15aR^15a, (CHR′

)_rNR^15fS(O)₂(CHR′

)_rR^15b, C_1-6 haloalkyl, C_2-8 alkenyl substituted with 0-3 R′

, C_2-8 alkynyl substituted with 0-3 R′

, (CHR′

)_rphenyl substituted with 0-3 R^15e, and a (CH₂)_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R^15e;

R′

, at each occurrence, is independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, and (CH₂)_rphenyl substituted with R^15e;

R^15a, at each occurrence, are selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-5 R^15e, and a (CH₂)_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R^{15 e};

R^15b, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-3 R^15e, and (CH₂)_r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R^15e;

R^15d, at each occurrence, is independently selected from C_2-8 alkenyl, C_2-8 alkynyl, C_1-6 alkyl substituted with 0-3 R^15e, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-3 R^15e, and a (CH₂)_r5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R^15e;

R^15e, 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, F, Br, I, CN, NO₂, (CF₂)_rCF₃, (CH₂)_rOC_1-5 alkyl, OH, SH, (CH₂)_rSC_1-5 alkyl, (CH₂)_rNR^15fR^15f, and (CH₂)_rphenyl;

R^15f, at each occurrence, is independently selected from H, C_1-6 alkyl, C_3-6 cycloalkyl, and phenyl;

R¹⁶, at each occurrence, is independently selected from C_1-8 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, Cl, Br, I, F, NO₂, CN, (CHR′

)_rNR^16aR^16a, (CHR′

)_rOH, (CHR′

)_rO(CHR′

)_rR^16d, (CHR′

)_rSH, (CHR′

)_rC(O)H, (CHR′

)_rS(CHR′

)_rR^16d, (CHR′

)_rC(O)OH, (CHR′

)_rC(O)(CHR′

)_rR^16b, (CHR′

)_rC(O)NR^16aR^16a, (CHR′

)_rNR^16fC(O)(CHR′

)_rR^16b, (CHR′

)_rC(O)O(CHR′

)_rR^16d, (CHR′

)_rOC(O)(CHR′

)_rR^16b, (CHR′

)_rC(═

NR^16f)NR^16aR^16a, (CHR′

)_rNHC(═

NR^16f)NR^16fR^16f, (CHR′

)_rS(O)_p(CHR′

)_rR^16b, (CHR′

)_rS(O)₂NR^16aR^16a, (CHR′

)_rNR^16fS(O)₂(CHR′

)_rR^16b, C_1-6 haloalkyl, C_2-8 alkenyl substituted with 0-3 R′

, C_2-8 alkynyl substituted with 0-3 R′

, and (CHR′

)_rphenyl substituted with 0-3 R^16e;

R^16a, at each occurrence, is independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-5 R^16e, and a (CH₂)_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R^16e;

R^16b, at each occurrence, is independently selected from C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, a (CH₂)_rC_3-6 carbocyclic residue substituted with 0-3 R^16e, and a (CH₂)_r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R^16e;

R^16d, at each ocurrence, is independently selected from C_2-8 alkenyl, C_2-8 alkynyl, C_1-6 alkyl substituted with 0-3 R^16e, a (CH₂)_r—

C_3-6 carbocyclic residue substituted with 0-3 R^16e, and a (CH₂)_r-5-6 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-3 R^16e;

R^16e, 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, F, Br, I, CN, NO₂, (CF₂)_rCF₃, (CH₂)_rOC_1-5 alkyl, OH, SH, (CH₂)_rSC_1-5 alkyl, (CH₂)_rNR^16fR^16f, and (CH₂)_rphenyl;

R^16f, at each occurrence, is independently selected from H, C_1-5 alkyl, and C_3-6 cycloalkyl, and phenyl;

R¹⁷ at each occurrence is independently selected from ═

O, C_1-6 alkyl, (CH₂)_rC_3-6 cycloalkyl, Cl, F, Br, I, CN, NO₂, (CH₂)_rOR¹⁹, (CH₂)_rOH, (CH₂)_rSR¹⁹, (CH₂)_rS(O)R¹⁹, (CH₂)_rS(O)₂R¹⁹, (CH₂)_rS(O)₂N(R^18a)R^18b, (CH₂)_rN(R^18c)C(O)R¹⁹(CH₂)_rN(R^18c)S(O)₂R¹⁹, (CH₂)_rC(O)OH, (CH₂)_rC(O)OR¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rN(R^18c)C(O)N(R^18a)R^18b, (CH₂)_rN(R^18c)C(O)OR¹⁹, (CH₂)_rOC(O)N(R^18a)R^18b, (CH₂)_rN(R^18a)R^18b, C_1-6 haloalkyl, C_2-8 alkenyl substituted with 0-3 R^17a, C_2-8 alkynyl substituted with 0-3 R^17a, (CH(R^17a))_rphenyl substituted with 1-3 R¹⁸, and (CH(R^17a))_r-5-10 membered heterocyclic system containing 1-4 heteroatoms selected from N, O, and S, substituted with 0-2 R¹⁸;

R^17a at each occurrence is independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, and (CH₂)_rphenyl substituted with 0-3 R¹⁸;

R¹⁸ 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, (CH₂)_rS(O)C_1-5 alkyl, (CH₂)_rS(O)₂C_1-5 alkyl, (CH₂)_rS(O)₂N(R^18a)R^18b, (CH₂)_rN(R^18c)C(O)C_1-5 alkyl, (CH₂)_rN(R^18c)S(O)₂C_1-5 alkyl, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rC(O)OC_1-5 alkyl, (CH₂)_rC(O)C_1-5 alkyl, and (CH₂)_rN(R^18a)R^18b;

R^18a, R^18b, and R^18c at each occurrence are independently selected from H, C_1-6 alkyl, and C_3-6 cycloalkyl;

R¹⁹ at each occurrence is independently selected from C_1-6 alkyl, C_3-6 cycloalkyl, and phenyl substituted with 0-3 R¹⁸;

alternatively, R^18a and R^18b along with the nitrogen to which both are attached form a pyrrolidine, piperidine, piperazine or morpholine ring;

R²⁵ at each occurrence is independently selected from H, C_1-6 alkyl, C_2-8 alkenyl, C_2-8 alkynyl, (CH₂)_rC_3-6 cycloalkyl, (CH₂)_rC(O)R¹⁹, (CH₂)_rC(O)N(R^18a)R^18b, (CH₂)_rC(O)OR¹⁹, (CH₂)_rS(O)₂R¹⁹, (CH₂)_rS(O)₂N(R^18a)R^18b, and (CH₂)_rphenyl substituted with 0-3 R¹⁷;

i is selected from 0, 1, and 2;

m is selected from 0, 1, and 2;

s is selected from 0 and 1;

with the proviso;

m+s is selected from 0, 1, and 2;

v is selected from 0, 1, 2, and 3;

with the proviso;

that the total number of atoms between the nitrogen of which R′

is attached and the fused ring B is less than or equal to 4;

r is selected from 0, 1, 2, 3, 4, and 5;

t is selected from 0, 1, 2, 3, 4, and 5;

q is selected from 1, 2, 3, 4, and 5;

p is selected from 1, 2, and 3;

u is selected from 0, 1 and, 2.

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)_rNR^6dR^6d;

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 (CR³′

H)_r—

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

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)

R¹⁰ is selected from H, methyl, ethyl, propyl, i-propyl, butyl, OH, and OR^10b;

and

R^10b is selected from methyl, ethyl, propyl, i-propyl, and butyl.

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 represent H.

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

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-[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 treating asthma, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 1.

15. 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.

16. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 7, or a pharmaceutically acceptable salt thereof.

17. A method for treating a disorder selected from asthma, allergic rhinitis, atopic dermatitis, inflammatory bowel diseases, idiopathic pulmonary fibrosis, bullous pemphigoid, allergic colitis, eczema, conjunctivitis, familial eosinophilia, eosinophilic cellulitis, eosinophilic pneumonias, eosinophilic fasciitis, and eosinophilic gastroenteritis, 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.

18. The method according to claim 17, wherein the disorder is selected from asthma, allergic rhinitis, atopic dermatitis, and inflammatory bowel diseases.

19. The method according to claim 18, wherein the disorder is asthma.

20. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound according to claim 7.

21. A method for treating asthma, comprising administering to a patient in need thereof a therapeutically effective amount of a compound according to claim 7.