Substituted pyridine compounds and methods of use
AssigneeAmgen Inc.
InventorsNathan B. Mantlo, Stephen T. Schlachter, John A. Josey
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Abstract
Selected novel substituted pyridine compounds are effective for prophylaxis and treatment of diseases, such as TNF-α, IL-1β, IL-6 and/or IL-8 mediated diseases, and other maladies, such as pain and diabetes. The invention encompasses novel compounds, analogs, prodrugs and pharmaceutically acceptable salts thereof, pharmaceutical compositions and methods for prophylaxis and treatment of diseases and other maladies or conditions involving inflammation, pain, diabetes, cancer and the like. The subject invention also relates to processes for making such compounds as well as to intermediates useful in such processes.
Claims11
A compound of the formula
- or a pharmaceutically acceptable salt thereof, wherein
- X is O, S, S(O), S(O)2 or NR2;
- Y is —C(O)—NR3R4 or —NR4—C(O)—R3;
- R1 is a heterocyclyl or heteroaryl radical which is optionally substituted by 1-4 radicals of alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R18—Z18— or R18—Z18—alkyl;
- provided that R1 is other than an optionally substituted pyridyl radical;
- and provided that the total number of aryl, heteroaryl, cycloalkyl and heterocyclyl radicals in R1 is 1-3;
- and provided when Y is —NR4—C(O)—R3 and X is O or S, R1 is other than a 2-pyrimidinyl radical;
- R2 is a hydrogen or alkyl radical;
- R3 is an aryl or heteroaryl radical which is optionally substituted by 1-5 radicals or alkyl, halo, haloalkyl, cyano, azido, nitro, amidino, R19—Z19— or R19—Z19—alkyl;
- provided that the total number of aryl and heteroaryl radicals in R3 is 1-3;
- and provided when Y is —C(O)—NR3R4, R3 is other than a phenyl or naphthyl having an amino, nitro, cyano, carboxy or alkoxycarbonyl substituent bonded to the ring carbon atom adjacent to the ring carbon atom bonded to —NR4—;
- and
- R4 is a hydrogen, alkyl, alkenyl, haloalkyl, haloalkenyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl or R20—Z20—alkyl radical;
- wherein R18, R19 and R20 are each independently a hydrogen, alkyl, haloalkyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl radical;
- wherein the aryl and heteroaryl radicals of R4, R18, R19 and R20 are optionally substituted by 1-3 radicals of hydroxy, alkoxy, alkylthiol, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, alkylsulfinyl, alkylsulfonyl, alkoxycarbonylamino, alkoxycarbonyl, cyano, halo, azido, alkyl, haloalkyl or haloalkoxy;
- and
- Z18, Z19 and Z20 are each independently —O—, —S—, —S(O)—, —S(O)2—, —CO2—, —C(O)—, —NR21—, —NR21—C(O)—, —C(O)—NR21—, —NR21—S(O)2— or —S(O)2—NR21—;
- wherein each R21 is independently a hydrogen or alkyl radical;
- R5 and R6 are each independently a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, amino, alkylamino, dialkylamino, alkanoylamino, alkylsulfonylamino, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical;
- and
- R7 is a hydrogen, alkyl, halo, haloalkyl, haloalkoxy, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl, aminosulfonyl, alkylaminosulfonyl, dialkylaminosulfonyl, hydroxy, hydroxyalkyl, thiol, alkylthiol, alkylsulfinyl, alkylsulfonyl, alkoxy, alkoxyalkyl, cyano, azido, nitro, carboxy, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl or dialkylaminocarbonyl radical.
Dependencies are inferred from the claim text.