发明名称 Compounds, pharmaceutical compositions and uses thereof
摘要 The present invention relates to compounds of general formula I,; wherein the groups R1, LP, LQ, X1, X2, X3, A, n and m are as defined in the application. The compounds of formula I have valuable pharmacological properties, and in particular bind to the GPR119 receptor and modulate its activity.
申请公布号 US8778926(B2) 申请公布日期 2014.07.15
申请号 US201213354356 申请日期 2012.01.20
申请人 Boehringer Ingelheim International GmbH 发明人 Himmelsbach Frank;Langkopf Elke;Nosse Bernd
分类号 A61K31/506;C07D491/048;C07D413/14;C07D407/14 主分类号 A61K31/506
代理机构 代理人 Morris Michael P.;Witkowski Timothy X.
主权项 1. A compound of formula (I) wherein: R1 is selected from the group consisting of a 5- or 6-membered heteroaromatic ring which contains 1, 2, or 3 heteroatoms independently selected from N, O, and S; and optionally a second ring is condensed to the heteroaromatic ring, wherein the second ring is unsaturated or aromatic and 5- or 6-membered and optionally contains 1, 2, or 3 heteroatoms independently selected from N, O, and S, and 1 or 2 —CH2— groups in the second ring are optionally replaced by —N(RN)—, —C(═O)—, —S(═O)—, or —S(═O)2—, the heteroaromatic ring and/or the second ring the H-atom in one or more NH groups is optionally replaced by RN, each of the heteroaromatic ring and/or the second ring are independently optionally substituted with one or more substituents selected from LA, and the heteroaromatic ring or the second ring are optionally substituted with a group RC; RN is independently H, C1-4-alkyl, C1-4-alkyl-C(═O)—, or C1-4-alkyl-S(═O)2—; A is selected from the group consisting of a 1,2,3,6-tetrahydropyridin-4-yl ring substituted at the N with C1-4-alkyl-S(═O)2—, a phenyl ring, and a 5- or 6-membered heteroaromatic ring which contains 1, 2, or 3 heteroatoms independently selected from N, O, and S, and optionally a second ring is condensed to the phenyl ring or heteroaromatic ring, wherein the second ring is unsaturated or aromatic and 5- or 6-membered and optionally contains 1, 2, or 3 heteroatoms independently selected from N, O, and S, and 1 or 2 —CH2— groups in the second ring are optionally replaced by —N(RN)—, —C(═O)—, —S(═O)—, or —S(═O)2—, the heteroaromatic ring and/or the second ring the H-atom in one or more NH groups are optionally replaced by RN, each of the phenyl ring, heteroaromatic ring, and/or second ring are independently optionally substituted with one or more substituents selected from LA, and the phenyl ring, heteroaromatic ring, or second ring are optionally substituted with a group T; T is selected from the group consisting of F, Cl, Br, I, CN, OH, NO2, C1-6-alkyl-, C1-6-alkenyl-, C1-6-alkynyl-, C3-6-cycloalkyl, C1-6-alkyl-O—, C3-6-cycloalkyl-O—, C1-6-alkyl-S—, HO—C(═O)—, C1-6-alkyl-O—C(═O)—, C1-4-alkyl-C(═O)—, C3-6-cycloalkyl-C(═O)—, C1-4-alkyl-S(═O)—, C1-4-alkyl-S(═O)2—, RNT1RNT2N—, RNT1RNT2N—C(═O)—, RNT1RNT2N—S(═O)2—, RNT1RNT2N—C(═O)—(RN)N—, heterocyclyl, heterocyclyl-O—, aryl, aryl-O—, heteroaryl, and heteroaryl-O—, wherein each alkyl, alkenyl, alkynyl, and cycloalkyl group is optionally substituted with one or more substituents independently selected from F, Cl, CN, OH, C1-3-alkyl, C3-6-cycloalkyl, C1-3-alkyl-O—, RNT1RNT2N—, RNT1RNT2N—C(═O)—, C1-4-alkyl-S(═O)—, C1-4-alkyl-S(═O)2—, RNT1RNT2N—S(═O)2—, aryl, heteroaryl, and heterocyclyl, wherein aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring which contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, the H-atom in one or more NH groups is optionally replaced by RN, heterocyclyl is a 4- to 7-membered unsaturated or saturated carbocyclic ring in which 1 or 2 —CH2-groups are independently replaced by NRN, O, —C(═O)—, S, —S(═O)—, or —S(═O)2—, and/or in which a —CH-group is replaced by N, and each aryl, heteroaryl, or heterocyclyl group is optionally substituted with one or more substituents independently selected from LA; RNT1 is selected from the group consisting of H, C1-6-alkyl, C3-6-cycloalkyl, C1-6-alkyl-C(═O)—, C1-6-alkyl-S(═O)2, heterocyclyl, aryl, and heteroaryl, wherein each alkyl and cycloalkyl group is optionally substituted with one or more substituents independently selected from the group consisting of F, OH, CN, C1-4-alkyl, C1-4-alkyl-O—, RN2N, C1-4-alkyl-S(═O)2—, C3-6-cycloalkyl, heterocyclyl, phenyl, and heteroaryl, heterocyclyl is optionally substituted with one or more substituents independently selected from F, C1-4-alkyl, RN2N, OH and C1-4-alkyl-O—, heterocyclyl is a C4-7-cycloalkyl ring in which 1 or 2 —CH2-groups are independently replaced by NRN, O, C(═O), S, S(═O), or S(═O)2, aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring which contains 1, 2, or 3 heteroatoms independently selected from N, O, and S, wherein the H-atom in one or more NH groups is optionally replaced by RN; and aryl and heteroaryl are optionally substituted with one or more substituents LA; RNT2 is H or C1-6-alkyl; or RNT1 and RNT2 are linked to form one group RNT1-RNT2— selected from the group consisting of a C3-5-alkylene group, wherein 1 or 2 —CH2-groups are independently replaced by NRN, O, C(═O), S, S(═O), or S(═O)2, optionally substituted with one or more substituents independently selected from F, C1-4-alkyl, (RN)2N, OH, and C1-4-alkyl-O—; LA is F, Cl, Br, CN, OH, NO2, C1-4-alkyl-, C1-4-alkyl-O—, (RN)2N—C(═O), (RN)2N—, or C1-4-alkyl-S(═O)2—, wherein each alkyl group is optionally substituted with one or more substituents independently selected from F, Cl, CN, OH, and C1-3-alkyl-O—; LP is F or C1-3-alkyl optionally substituted with one or more F-atoms; LQ is F or C1-3-alkyl optionally substituted with one or more F-atoms; RC is F, Cl, Br, I, CN, OH, NO2, C1-6-alkyl-, C1-6-alkenyl-, C1-6-alkynyl-, C3-6-cycloalkyl, C1-6-alkyl-O—, C3-6-cycloalkyl-O—, C1-6-alkyl-S—, HO—C(═O)—, C1-6-alkyl-O—C(═O)—, C1-4-alkyl-C(═O)—, C3-6-cycloalkyl-C(═O)—, C1-4-alkyl-S(═O)—, C1-4-alkyl-S(═O)2—, RNT1RNT2N—, RNT1RNT2N—C(═O)—, RNT1RNT2N—S(═O)2—, RNT1RNT2N—C(═O) (RN)N—, heterocyclyl, heterocyclyl-O—, aryl, aryl-O—, heteroaryl, and heteroaryl-O—, wherein each alkyl, alkenyl, alkynyl, and cycloalkyl group is optionally substituted with one or more substituents independently selected from F, Cl, CN, OH, C1-3-alkyl, C3-6-cycloalkyl, C1-3-alkyl-O—, RNT1RNT2N—, RNT1RNT2N—C(═O)—, C1-4-alkyl-S(═O)—, C1-4-alkyl-S(═O)2—, RNT1RNT2N—S(═O)2—, aryl, heteroaryl, and heterocyclyl, aryl is phenyl or naphthyl, heteroaryl is a 5- or 6-membered aromatic ring which contains 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein the H-atom in one or more NH groups is optionally replaced by RN, heterocyclyl is a 4- to 7-membered unsaturated or saturated carbocyclic ring in which 1 or 2 —CH2— groups are independently replaced by NRN, O, —C(═O)—, S, —S(═O)—, or —S(═O)2—, and/or in which a —CH-group is replaced by N, and each aryl, heteroaryl, or heterocyclyl group is optionally substituted with one or more substituents independently selected from LA; X1, X2, and X3 are independently C(R2) or N, such that 1 or 2 members of the group consisting of X1, X2, and X3 is N; R2 is H, F, Cl, CN, OH, C1-4-alkyl, F2HC, F3C, C1-4-alkyl-O—, F2HC—O—, F3C—O—, or C3-7-cycloalkyl-O—; n is 0, 1, 2, 3, or 4; and m is 0, 1, or 2; or a salt thereof.
地址 Ingelheim am Rhein DE