4-6-diphenyl pyridine derivatives as antiinflammatory agents

A 4-aryl pyridine derivative of the formula (I):

• wherein
• X is CH;
• R1 is hydrogen, hydroxy, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, nitro, amino, mono or di (C1-6 alkyl)amino, phenylsulfonylamino, —NHR11 or —O—(CH2)n—R12,
• wherein
• R11 is phenyl substituted C1-6 alkyl, C1-6 alkanoyl or C1-6alkylsulfonyl,
• n represents an integer selected from 0 to 6, and
• R12 is C2-6 alkenyl, benzoyl, mono or di phenyl, mono or di (C1-6 alkyl)-amino, C1-6 alkanoyl, C1-6 alkoxycarbonyl, or a 3 to 10 membered saturated or unsaturated ring having 0 to 3 heteroatoms selected from the group consisting of S, O and N, and said ring is optionally substituted by hydroxy, nitro, cyano, mono or di halogen, C1-6 alkyl, halogen substituted C1-6 alkyl, amino, mono or di (C1-6 alkyl)amino, C1-6 alkanoylamino, carbamoyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, or phenyl;
• R2 is hydrogen, hydroxy, halogen, or C1-6 alkyl;
• R3 is hydrogen, hydroxy, halogen, C1-6 alkoxy, C3-6 cycloalkyl substituted C1-6 alkyloxy, —N R31R32, or a 3 to 6 membered saturated ring having 0 to 3 heteroatoms selected from the group consisting of O and N, and said ring is optionally substituted by R33;
• wherein
• R31 is hydrogen or C1-6 alkyl
• R32 is hydrogen, C1-6 alkanoyl, or C1-6 alkyl optionally substituted by hydroxy or phenyl,
• R33 is nitro, cyano, C1-6 alkyl optionally substituted by hydroxy or amino, C1-6 alkoxy, hydroxy substituted C1-6 alkyloxy, amino substituted C1-6 alkyloxy, C1-6 alkanoyl, carbamoyl or —NR33aR33b
• wherein
• R33a is hydrogen or C1-6 alkyl
• R33b is hydrogen, C1-6 alkyl optionally substituted by hydroxy or phenyl, C1-6 alkanoyl, C1-6 alkylsulfonyl, or trifluoroacetyl,
• R4 is —NH—COR41,
• wherein
• R41 is C1-6 alkyl optionally substituted by R41a, C1-6 alkoxy, oxotetrahydrofuryl, oxopyrrolidinyl, —CH(OH)R41b, —CH(NH2)R41c, —NHR41c, or piperazino optionally substituted by R41d,
• wherein
• R41a is carboxy, C1-6 alkoxy, —CH(NH2)carboxy, —NR41a-1R41a-2, or a 3 to 10 membered saturated ring having 0 to 3 heteroatoms selected from the group consisting of O and N, and said ring is optionally substituted by carboxy, C1-6 alkyl optionally substituted by hydroxy or benzodioxane, C3-6 cycloalkyl, C1-6 alkanoyl, carboxy, benzyl, C1-6 alkoxycarbonyl, or furoyl,
• wherein
• R41a-1 is hydrogen or C1-6 alkyl optionally substituted by hydroxy, C1-6 alkyloxy, C3-8 cycloalkyl, or piperidino,
• R41a-2 is hydrogen or C1-6 alkyl optionally substituted by hydroxy, C1-6 alkyloxy or C3-6 cycloalkyl, C1-6 alkoxy or a 3 to 6 membered saturated ring having 0 to 3 heteroatoms selected from the group consisting of O and N, and said ring is optionally substituted by carboxy, C1-6 alkyl, C1-6 alkanoyl, or C1-6 alkyloxy,
• R41b is C1-6 alkyl optionally substituted by carboxy or C1-6 alkyloxy, C1-6 alkoxy, or C1-6 alkoxycarbonyl,
• R41c is carboxy, C1-6 alkyl optionally substituted by carboxy or a 3 to 6 membered saturated ring having 0 to 3 heteroatoms selected from the group consisting of O and N, or
• R41d is C1-6 alkyl optionally substituted by carboxy or C1-6 alkyloxy, or C1-6 alkoxy
• R42 is C1-6 alkoxy, carboxy, amino, —CH(NH2)-carboxy or a 5 to 7 membered saturated or unsaturated ring having 0 to 3 heteroatoms selected from the group consisting of O and N, and said ring is optionally substituted by hydroxy, nitro, mono or di halogen, C1-6 alkyl, halogen substituted C1-6 alkyl, amino, mono or di (C1-6 alkyl)amino,or carbamoyl;
• R43 is carboxy, amino, —CH(NH2)-carboxy or a 5 to 7 membered saturated or unsaturated ring having 0 to 3 heteroatoms selected from the group consisting of O and N, and said ring is optionally substituted by hydroxy, nitro, mono or di halogen, C1-6 alkyl, halogen substituted C1-6 alkyl, amino, mono or di (C1-6 alkyl)amino, or carbamoyl;
• or
• R3 and R4 may form, together with the carbon atoms in the benzene ring, a 4 to 6 membered saturated ring having 0 to 3 heteroatoms selected from the group consisting of O and N, and said ring is optionally substituted by one or more substituents selected from the group consisting of hydroxy, nitro, mono or di halogen, C1-6 alkyl, halogen substituted C1-6 alkyl, oxo, amino, mono or di (C1-6 alkyl)amino, and carbamoyl;
• R5 is hydrogen, cyano, carboxy, carbamoyl, C1-6 alkyl optionally substituted by hydroxy or carbamoyl, and C1-6 alkoxycarbonyl, and
• R6 is amino or acetamido
• or
• R5 and R6 may form, together with the carbon atoms in the pyridine ring, a 5 to 7 membered saturated or unsaturated ring having 0 to 3 heteroatoms selected from the group consisting of O, S and N, and said ring optionally having substituents selected from the group consisting of halogen, nitro, cyano, oxo, thioxo, C1-6 alkyl, C1-6 alkylsulfonyl, C1-6 alkoxy, C1-6 alkoxycarbonyl, phenyl, C1-6 alkanoyl, amino, C1-6 alkylamino, C1-6 alkanoylamino, carbamoyl, C3-8 cycloalkylaminocarbonyl, C1-6 alkylaminocarbonyl, halogen substituted C1-6 alkylaminocarbonyl, di (C1-6 alkyl)aminocarbonyl, benzoylamino, phenylsulfonyl, di(C1-6 alkyl)aminoC1-6 alkylaminocarbonyl, hydroindenylaminocarbonyl, diphenylmethylaminocarbonyl, pyrrolidinocarbonyl, C1-6 alkyloxy C1-6 alkyl amino carbonyl, morpholinocarbonyl, piperazinocarbonyl, phenylC1-6 alkylaminocarbonyl, carboxyC1-6 alkylaminocarbonyl, C3-8 cycloalkylC1-6 alkylaminocarbonyl, hydroxy C1-6alkylaminocarbonyl, and methylsulfonylaminocarbonyl
• or a salt thereof.