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US 8,476,283 B2Granted
[6,5]—bicyclic GPR119 G protein-coupled receptor agonists
AssigneeBristol-Myers Squibb Company
InventorsJohn M. Fevig, Dean A. Wacker
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: or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein n2, n3, n4, A, B, D, E, G, J, Y, R1 and R2 are defined herein.
Claims12
A compound of Formula Ia
- or an enantiomer, diastereomer or pharmaceutically acceptable salt thereof wherein:
- A and D are N;
- B is CR4b;
- E is N and NH;
- G is N;
- J is CR9R9 or CR9;
- the dashed line represents an optional double bond, provided that J is not CR9R9 when a double bond is present;
- Y is —NR3, O or S;
- n2 and n3 are each independently 0-2;
- R1 is aryl which may be optionally substituted with one or more substituents selected from R4;
- R2 is selected from the group consisting of cycloalkyl, aryl, heteroaryl, heterocyclyl, —C(═O)R5 and —C(═O)OR5, wherein the cycloalkyl, aryl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R6's;
- R3 is selected from the group consisting of hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl;
- R4, at each occurrence, is independently selected from the group consisting of alkyl, aryl, alkenyl, alkynyl, cycloalkyl, heteroaryl, heterocyclyl, halo, —CN, —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, —OC(═O)NR9R9, —C(═NR14)NR9R9, —NHC(═NR14)NR14R14, —S(═O)R10, —S(O)2R10, —NR9C(═O)OR8 and —NR9S(O2)R8, wherein the alkyl, aryl, alkenyl, alkynyl, cycloalkyl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R6's;
- R4b, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, haloalkyl, aryl, alkenyl, alkynyl, cycloalkyl, heteroaryl, 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, —OC(═O)NR9R9, —C(═NR14)NR9R9, —NHC(═NR14)NR14R14, —S(═O)R10, —S(O)2R10, —NR9C(═O)OR8 and —NR9S(O2)R8, wherein the alkyl, aryl, alkenyl, alkynyl, cycloalkyl, heteroaryl and heterocyclyl may each be optionally substituted with one or more R6's;
- R5 is selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl, each of which may optionally be substituted with one or more R6's;
- R6, at each occurrence, is independently selected from the group consisting of 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, —NR9C(═O)OR8 and —NR9S(O2)R8;
- R8, at each occurrence, is independently selected from the group consisting of alkyl, aryl, cycloalkyl, heteroaryl and heterocyclyl;
- R9, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, alkoxy, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R9a, and the heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl each contain 1-4 heteroatoms selected from N, O and S;
- R9a, at each occurrence, is independently selected from the group consisting of 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 and arylalkyl;
- R10, at each occurrence, is independently selected from the group consisting of alkyl, cycloalkyl, alkenyl, alkynyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl, wherein the aryl, arylalkyl, heterocyclyl and heterocyclylalkyl may each be optionally substituted with 0-5 R10a, and the heterocyclyl and heterocyclylalkyl each contain 1-4 heteroatoms selected from N, O and S;
- R10a, at each occurrence, is independently selected from the group consisting of 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;
- and
- R14, at each occurrence, is independently selected from the group consisting of hydrogen, alkyl, cycloalkyl and aryl.
20 more elements
Dependencies are inferred from the claim text.