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) below:

• 61
• wherein:
• R1 is hydrogen, azido, halogen, C1-5 alkoxy, hydroxy, C1-5 alkyl, C2-5 alkenyl, cyano, nitro, R7R8N, C2-8 acyl, R9OC═O, R10R11NC═O, or R10R11NSO2;
• or
• R1 is taken together with W as described below;
• R2 is hydrogen, halogen, C1-5 alkoxy, C1-5 alkyl, C2-5 alkenyl, C1-5 haloalkyl, cyano, or R48R49N;
• alternatively, R1 and R2 can be taken together to form an optionally substituted 5- to 7-membered carbocyclic or heterocyclic ring, which ring may be unsaturated or aromatic;
• each of R3 and R4 is independently hydrogen or C1-5 alkyl;
• each of R5 and R6 is independently hydrogen, C1-5 alkyl, C2-5 alkenyl, C1-5 alkoxy, C1-5 alkylthio, halogen, or a 4-7 membered carbocyclyl or heterocyclyl;
• alternatively, R5 and R6 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, nitro, R40, R40O—, R40S—, R40O(C1-5 alkylene)-, R40O(C═O)—, R40(C═O)—, R40(C═S)—, R40(C═O)O—, R40O(C═O)(C═O)—, R40SO2, NHR62(C═NH)—, NHR62SO2—, and NHR62(C═O)—;
• R40 is H, C1-5 alkyl, C2-5 alkenyl, phenyl, benzyl, phenethyl, C1-5 heterocyclyl, (C1-5 heterocyclyl)C1-5 alkylene, amino, or mono- or di(C1-5 alkyl)amino, or R58OR59—, wherein R58 is H, C1-5 alkyl, C2-5 alkenyl, phenyl, benzyl, phenethyl, C1-5 heterocyclyl, or (C1-5 heterocyclyl)C1-6 alkylene and R59 is C1-5 alkylene, phenylene, or divalent C1-5 heterocyclyl;
• and
• R62 can be H in addition to the values for R40;
• R7 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, naphthyl, C1-5 heterocyclyl, C2-8 acyl, aroyl, R27OC═O, R28R29NC═O, R27SO, R27SO2, or R28R29NSO2;
• R8 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, or C1-5 heterocyclyl;
• alternatively, R7 and R8 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• R9 is C1-5 alkyl, phenyl, naphthyl, or C1-5 heterocyclyl;
• R21 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, naphthyl, C1-5 heterocyclyl, C2-8 acyl, aroyl, R30OC═O, R31R32NC═O, R30SO, R30SO2, or R31R32NSO2;
• R22 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, or C1-5 heterocyclyl;
• alternatively, R21 and R22 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 R23, R26, R27, R30, R33, R44, R45, and R50 is C1-5 alkyl, phenyl, naphthyl, or C1-5 heterocyclyl;
• R24 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, naphthyl, C1-5 heterocyclyl, C2-8 acyl, aroyl, R33OC═O, R34R35NC═O, R33SO, R33SO2, or R34R35NSO2;
• R25 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, or C1-5 heterocyclyl;
• alternatively, R24 and R25 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 R10 and R11 is independently hydrogen, C1-5 alkyl, C2-5 alkenyl, phenyl, or C1-5 heterocyclyl;
• alternatively, R10 and R11 or 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 R28, R29, R31, R32, R34, R35, R46, R47, R51 and R52 is independently hydrogen, C1-5 alkyl, phenyl, or C1-5 heterocyclyl;
• alternatively, R28 and R29, R31 and R32, R34 and R35, R46 and R47, or R51 and R52, independently, can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• n is 1 or 2;
• G represents C3-6 alkenediyl or C3-6 alkanediyl, optionally substituted with hydroxy, halogen, C1-5 alkyl, C1-5 alkoxy, oxo, hydroximino, CO2R60, R60R61NCO2, (L)-C1-4 alkylene-, (L)-C1-5 alkoxy, N3, or [(L)-C1-5 alkylene]amino;
• each of R60 and R61 is independently hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl, phenethyl, or C1-5 heterocyclyl;
• alternatively R60 and R61, 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, where available ring nitrogens may be optionally substituted with C1-5 alkyl, benzyl, C2-5 acyl, C1-5 alkylsulfonyl or C1-5 alkyloxycarbonyl;
• X is nitrogen or R12C;
• Y is nitrogen or R13C;
• Z is nitrogen or R14C;
• R12 is hydrogen, halogen, C1-5 alkoxy, C1-5 alkyl, C2-5 alkenyl, cyano, nitro, R21R22N, C2-8 acyl, C1-5 haloalkyl, C1-5 heterocyclyl, (C1-5 heterocyclyl)C1-5 alkylene, R23OC═O, R23O(C═O)NH—, R23SO, R22NHCO—, R22NH(C═O)NH—, R23(C1-4 alkylene)NHCO—, R23SO2, or R23SO2NH—;
• R13 is hydrogen, halogen, C1-5 alkoxy, C1-5 alkyl, C2-5 alkenyl, cyano, nitro, R42R43N, C2-8 acyl, C1-5 haloalkyl, C1-5 heterocyclyl, (C1-5 heterocyclyl)C1-5 alkylene, R44OC═O, R44O(C═O)NH—, R44SO, R43NHCO—, R43NH(C═O)NH—, R44(C1-4 alkylene)NHCO—, R44SO2, or R44SO2NH—;
• R14 is hydrogen, halogen, C1-5 alkoxy, C1-5 alkyl, C2-5 alkenyl, cyano, nitro, R24R25N, C2-8 acyl, C1-5 haloalkyl, C1-5 heterocyclyl, (C1-5 heterocyclyl)C1-5 alkylene, R26OC═O, R26O(C═O)NH—, R26SO, R25NHCO—, R25NH(C═O)NH—, R26(C1-4 alkylene)NHCO—, R26SO2, or R26SO2NH—;
• alternatively, R12 and R13 or R12 and R2 or R13 and R14 can be taken together to form an optionally substituted 5- to 6-membered carbocyclic or heterocyclic ring, which ring may be unsaturated or aromatic;
• Ar represents a monocyclic or bicyclic aryl or heteroaryl ring, optionally substituted with between 1 and 3 substituents selected from halogen, C1-5 alkoxy, C1-5 alkyl, C2-5 alkenyl, cyano, azido, nitro, R15R16N, R17SO2, R17S, R17SO, R17OC═O, R15R16NC═O, C1-5 haloalkyl, C1-5 haloalkoxy, C1-5 haloalkylthio, and C1-5 alkylthio;
• R15 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl, C1-5 heterocyclyl, C2-8 acyl, aroyl, R53OC═O, R54R55NC═O, R53S, R53SO, R53SO2, or R54R55NSO2;
• R16 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, benzyl, or C1-5 heterocyclyl;
• alternatively, R15 and R16 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 R17 and R53 is C1-5 alkyl, phenyl, or C1-5 heterocyclyl;
• each of R54 and R55 is independently hydrogen, C1-5 alkyl, C2-5 alkenyl, phenyl, benzyl, or C1-5 heterocyclyl;
• alternatively, R54 and R55 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 SO2, C═O, CHR20, or a covalent bond;
• or W and R1, taken together with the 6-membered ring to which they are both attached, form one of the following two formulae:
• 62
• wherein Xa is O, S, or N;
• and Xb is O, S or SO2;
• R20 is hydrogen, C1-5 alkyl, phenyl, benzyl, naphthyl, or C1-5 heterocyclyl;
• R42 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, naphthyl, C1-5 heterocyclyl, C2-8 acyl, aroyl, R45OC═O, R46R47NC═O, R45SO, R45SO2, or R46R47NSO2;
• R43 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, or C1-5 heterocyclyl;
• alternatively, R42 and R43 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• R44 is C1-5 alkyl, C2-5 alkenyl, phenyl, naphthyl, or C1-5 heterocyclyl;
• R48 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, naphthyl, C1-5 heterocyclyl, C2-8 acyl, aroyl, R50OC═O, R51R52NC═O, R50SO, R50SO2, or R51R52NSO2;
• R49 is hydrogen, C1-5 alkyl, C3-5 alkenyl, phenyl, or C1-5 heterocyclyl;
• alternatively, R48 and R49 can be taken together to form an optionally substituted 4- to 7-membered heterocyclic ring, which ring may be saturated, unsaturated or aromatic;
• and
• 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, ester, or amide thereof.