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US 2012/0258959 A1Published application
Pyridone gpr119 g protein-coupled receptor agonists
AssigneeBristol-Myers Squibb Company
InventorsDean A. Wacker, Karen A. Rossi, Ying Wang
Life of this patent
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Abstract
Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. These novel compounds have the structure Formula I or Formula IA.
Claims16
A compound selected from compounds of Formula I and Formula IA:
- and enantiomers, diastereomers, solvates and pharmaceutically acceptable salts thereof having ring A and ring B, wherein:
- ring A is optionally substituted with one or more R's shown as R20 and R21;
- G is CH or N;
- Q is C;
- X is N;
- Y is CH2, N(R3), C(═O), O, OCR9R9, S, S(═O) or S(O)2;
- n1 is 0-2;
- n2 is 0-2;
- n3 is 1-2;
- R1 is a 6-membered monocyclic aryl, a 5-membered monocyclic heteroaryl or a 6-membered monocyclic heteroaryl, each of which may be optionally substituted with one or more members selected from R1a, R1b, R1c, R1d and R1e;
- R1a, R1b, R1c, R1d and R1e are each independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR10, —OCF3, —OR11, —OH, —SH, —SR11, —S(O)3H, —P(O)3H2, —C(═O)NR9R9, —NR12R12, —S(O)2NR9R9, —NR9S(O)2CF3, —C(═O)NR9S(O)2R9, —S(O)2NR9C(═O)OR9, —S(O)2NR9C(═O)NR9R9, —C(═O)NR9S(O)2CF3, —C(═O)R11, —NR9C(═O)H, —NR9C(═O)R10, —OC(═O)R10, —OC(═O)NR9R9, —C(═NR14)NR9R9, —NHC(═NR14)NR14R14, —S(═O)R11, —S(O)2R11, —NR9C(═O)OR8 and —NR9S(O2)R8, wherein:
- (a) the alkenyl, alkynyl, cycloalkyl, aryl and heterocyclyl may each be optionally substituted with one or more R6's;
- and (b) the alkyl may optionally be substituted by one or more of R7's;
- R2 is cycloalkyl, aryl, heteroaryl, heterocyclyl, —S(O)2R5, —C(═O)NR3R5, —C(═O)R5 or —C(═O)OR5, wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R6's;
- R3 is hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl;
- R5 is alkyl, alkenyl, aryl, cycloalkyl, heteroaryl or heterocyclyl, each of which may be optionally substituted with one or more R6's;
- R6, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR10, —OCF3, —OR10, —OH, —SH, —SR10, —S(O)3H, —P(O)3H2, —C(═O)NR9R9, —NR9R9, —S(O)2NR9R9, —NR9S(O)2CF3, —C(═O)NR9S(O)2R9, —S(O)2NR9C(═O)OR9, —S(O)2NR9C(═O)NR9R9, —C(═O)NR9S(O)2CF3, —C(═O)R10, —NR9C(═O)H, —NR9C(═O)R10, —OC(═O)R10, —C(═NR14)NR9R9, —NHC(═NR14)NR14R14, —S(═O)R10, —S(O)2R10, ═O, —NR9C(═O)OR8 and —NR9S(O2)R8, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R9a;
- R7, at each occurrence, is independently selected from the group consisting of alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heterocyclyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR10, —OCF3, —OR10, —OH, —SH, —SR10, —S(O)3H, —P(O)3H2, —C(═O)NR9R9, —NR9R9, —S(O)2NR9R9, —NR9S(O)2CF3, —C(═O)NR9S(O)2R9, —S(O)2NR9C(═O)OR9, —S(O)2NR9C(═O)NR9R9, —C(═O)NR9S(O)2CF3, —C(═O)R10, —NR9C(═O)H, —NR9C(═O)R10, —OC(═O)R10, —C(═NR14)NR9R9, —NHC(═NR14)NR14R14, —S(═O)R10, —S(O)2R10, ═O, —NR9C(═O)OR8 and —NR9S(O2)R8, wherein the alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkylalkyl and heterocyclyl may each be optionally substituted with 0-5 R9a;
- R8, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may be optionally substituted with one or more R8a's;
- R8a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR14, —OCF3, —OR14, —OH, —SH, —SR14, —S(O)3H, —P(O)3H2, —C(═O)NR14R14, —NR14R14, —S(O)2NR14R14, —NR14S(O)2CF3, —C(═O)NR14S(O)2R14, —S(O)2NR14C(═O)OR14, —S(O)2NR14C(═O)NR14R14, —C(═O)NR14S(O)2CF3, —C(═O)R14, —NR14C(═O)H, —NR14C(═O)R14, —OC(═O)R14, —C(═NR14)NR14R14, —NHC(═NR14)NR14R14, —S(═O)R14, —S(O)2R14, ═O, —NR14C(═O)OR14 and —NR14S(O2)R14;
- R9, at each occurrence, is independently selected from hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R9a;
- R9a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR14, —OCF3, —OR14, —OH, —SH, —SR14, —S(O)3H, —P(O)3H2, —C(═O)NR14R14, —NR14R14, —S(O)2NR14R14, —NR14S(O)2CF3, —C(═O)NR14S(O)2R10, —S(O)2NR14C(═O)OR10, —S(O)2NR14C(═O)NR14R14, —C(═O)NR14S(O)2CF3, —C(═O)R14, —NR14C(═O)H, —NR14C(═O)R14, —OC(═O)R14, —C(═NR14)NR14R14, —NHC(═NR14)NR14R14, —S(═O)R14, —S(O)2R14, —NR14C(═O)OR8, —NR14S(O2)R8, ═O and arylalkyl;
- R10, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R10a;
- R10a, at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR14, —OCF3, —OR14, —OH, —SH, —SR14, —S(O)3H, —P(O)3H2, —C(═O)NR14R14, —NR14R14, —S(O)2NR14R14, —NR14S(O)2CF3, —C(═O)NR14S(O)2R9, —S(O)2NR14C(═O)OR9, —S(O)2NR14C(═O)NR14R14, —C(═O)NR14S(O)2CF3, —C(═O)R14, —NR14C(═O)H, —NR14C(═O)R14, —OC(═O)R14, —C(═NR14)NR14R14, —NHC(═NR14)NR14R14, —S(═O)R14, —S(O)2R14, —NR14C(═O)OR8, —NR14S(O2)R8 and arylalkyl;
- R11, at each occurrence, is independently selected from alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R11a;
- R10a at each occurrence, is independently selected from alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, —NH2, —CN, —NO2, —C(═O)OH, —C(═O)OR14, —OCF3, —OR14, —OH, —SH, —SR14, —S(O)3H, —P(O)3H2, —C(═O)NR14R14, —NR14R14, —S(O)2NR14R14, —NR14S(O)2CF3, —C(═O)NR14S(O)2R9, —S(O)2NR14C(═O)OR9, —S(O)2NR14C(═O)NR14R14, —C(═O)NR14S(O)2CF3, —C(═O)R14, —NR14C(═O)H, —NR14C(═O)R14, —OC(═O)R14, —C(═NR14)NR14R14, —NHC(═NR14)NR14R14, —S(═O)R14, —S(O)2R14, —NR14C(═O)OR8, —NR14S(O2)R8 and arylalkyl;
- R12, at each occurrence, is independently selected from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl, wherein the cycloalkyl, aryl, arylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-3 R10a;
- R14, at each occurrence, is independently selected from hydrogen, alkyl, cycloalkyl and aryl;
- and
- R20 and R21 are each independently selected from the group consisting of hydrogen, alkyl, haloalkyl, cycloalkyl, phenyl, halo, —CN, —C(═O)OH, —C(═O)OR10, —OCF3, —OR10, —OH, —C(═O)NR9R9, —C(═O)R10 and —OC(═O)R10.
27 more elements
A compound of the formula
Dependencies are inferred from the claim text.