Method for treating allergies using substituted pyrazoles

A method for treating a subject with an allergic condition, said method comprising administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising a compound of formula (I):

• wherein:
• Ar2 is a monocyclic or bicyclic ring system, unsaturated, saturated or aromatic, optionally fused, optionally including between 1 and 5 heteroatom ring moieties independently selected from O, S, N, SO2, and C═O;
• said Ar2 ring system being optionally substituted with between 1 and 4 substituents;
• R5 and R6 are independently selected from hydrogen and C1-5 alkyl;
• R7 and R8 are independently hydrogen, C1-5 alkyl, C2-5 alkenyl, C1-5 alkoxy, C1-5 alkylthio, halogen, or a 4-7 membered carbocyclyl or heterocyclyl;
• alternatively, R7 and R8 can be taken together to form an optionally substituted 5- to 7-membered carbocyclic or heterocyclic ring, which ring may be unsaturated or aromatic, and may be optionally substituted with between one and three substituents independently selected from halo, cyano, amino, hydroxy, nitro, R4, R4O—, R4S—, R4O(C1-5 alkylene)—, R4O(C═O)—, R4(C═O)—, R4(C═S)—, R4(C═O)O—, R4O(C═O)(C═O)—, R4SO2, NHR44(C═NH)—, NHR44SO2—, and NHR44(C═O)—;
• R4 is H, C1-5 alkyl, C2-5 alkenyl, C1-5 heterocyclyl, (C1-5 heterocyclyl)C1-6 alkylene, phenyl, benzyl, phenethyl, NH2, mono- or di(C1-6 alkyl)N—, (C1-6 alkoxy)carbonyl- or R42OR43—, wherein R42 is H, C1-5 alkyl, C2-5 alkenyl, phenyl, benzyl, phenethyl, C1-5 heterocyclyl, or (C1-5 heterocyclyl)C1-6 alkylene and R43 is C1-5 alkylene, phenylene, or divalent C1-5 heterocyclyl;
• R44 can be H in addition to the values for R4;
• n is 0, 1, or 2;
• G is C3-6 alkenediyl or C3-6 alkanediyl, optionally substituted with hydroxy, halogen, C1-5 alkoxy, C1-5 alkyl, oxo, hydroximino, CO2Rk, RkRlN, RkRlNCO2, (L)-C1-4 alkylene-, (L)-C1-5 alkoxy, N3, or [(L)-C1-5 alkylene]amino;
• each of Rk and Rl is independently hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl, phenethyl, or C1-5 heterocyclyl;
• alternatively Rk and Rl, can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• L is amino, mono- or di-C1-5 alkylamino, pyrrolidinyl, morpholinyl, piperidinyl homopiperidinyl, or piperazinyl, wherein available ring nitrogens may be optionally substituted with C1-5 alkyl, benzyl, C2-5 acyl, C1-5 alkylsulfonyl, or C1-5 alkoxycarbonyl;
• Ar represents a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with between 1 and 3 substituents independently selected from halogen, C1-5 alkoxy, C1-5 alkyl, C2-5 alkenyl, cyano, azido, nitro, R22R23N, R24SO2, R24S, R24SO, R24OC═O, R22R23NC═O, C1-5 haloalkyl, C1-5 haloalkoxy, C1-5 haloalkylthio, and C1-5 alkylthio;
• R22 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, phenethyl, benzyl, or C1-5 heterocyclyl, C2-8 acyl, aroyl, R38OC═O, R25R26NC═O, R38SO, R38S2, R38S, or R25R26NSO2;
• R23 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl or C1-5 heterocyclyl;
• alternatively, R22 and R23 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• each of R24 and R24 is C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl, or C1-5 heterocyclyl;
• R25 and R26 independently are hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl, or C1-5 heterocyclyl;
• or, alternatively, R25 and R26 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• W represents O, S, NR27, C═O, (C═O)NH, NH(C═O), CHR28, or a covalent bond;
• Rz is H or OH and the dashed line is absent;
• or Rz is absent where the dashed line is an sp2 bond;
• R27 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, naphthyl, benzyl, phenethyl,
• C1-5 heterocyclyl, C2-8 acyl, aroyl, R29OC═O, R30R31NC═O, R29SO, R29S, R29SO2, or R30R31NSO2;
• or, alternatively, R27 and part of Ar2 can be taken together to form an optionally substituted 5- or 6-membered heterocyclic ring with optionally 1 to 3 additional heteroatom moieties in the ring selected from O, NR9, NR10, N, SO2, C═O, and S;
• which ring may be saturated, unsaturated or aromatic;
• R9 and R10 are independently selected from H, C1-3 alkyl, and —CH2CO2(C1-4 alkyl);
• R28 is hydrogen, C1-5 alkyl, C3-5 alkenyl, hydroxy, phenyl, benzyl, C1-5 heterocyclyl, R29O, R30R31NC═O, R29S, R29SO, R29SO2, or R30R31NSO2;
• R29 is C1-5 alkyl, C3-3 alkenyl, phenyl, benzyl, or C1-5 heterocyclyl;
• R30 and R31 are independently selected from hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl, phenethyl, naphthyl, and C1-5 heteroaryl;
• alternatively, R30 and R31 can be taken together to form an optionally substituted 4- to 7-membered ring carbocyclic or heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• wherein each of the above hydrocarbyl or heterocarbyl groups, unless otherwise indicated, and in addition to any specified substituents, is optionally and independently substituted with between 1 and 3 substituents selected from methyl, halomethyl, hydroxymethyl, halo, hydroxy, amino, nitro, cyano, C1-5 alkyl, C1-5 alkoxy, —COOH, C2-6 acyl, [di(C1-4 alkyl)amino]C2-5 alkylene, [di(C1-4 alkyl)amino]C2-5 alkyl-NH—CO—, and C1-5 haloalkoxy;
• or a pharmaceutically acceptable salt, amide, or ester thereof;
• or a stereoisomeric form thereof.