发明名称 Tetrahydroisoquinoline derivatives, pharmaceutical compositions and uses thereof
摘要 The invention relates to new pyrrolidine derivatives of the formula; wherein R1 to R6, n and m are as defined in the description and claims, to their use as medicaments, to methods for their therapeutic use and to pharmaceutical compositions containing them.
申请公布号 US9340510(B2) 申请公布日期 2016.05.17
申请号 US201514855668 申请日期 2015.09.16
申请人 Boehringer Ingelheim International GmbH 发明人 Roth Gerald Juergen;Fleck Martin;Haebel Peter Wilhelm;Heimann Annekatrin;Heine Niklas
分类号 C07D217/18;C07D417/12;A61K31/47 主分类号 C07D217/18
代理机构 代理人 Morris Michael P.;Stempel Alan R.
主权项 1. A compound of formula (I) wherein R1 is selected from a group consisting of: halogen, CN, OH, C1-6-alkyl, C3-7-cycloalkyl, —(C1-3-alkyl)-(C3-7-cycloalkyl), —O—(C1-6-alkyl), —O—(C3-7-cycloalkyl), —O—(C1-3-alkyl)-(C3-7-cycloalkyl), —O-phenyl, —O—(C1-3-alkyl)-phenyl, —COOH, —COO(C1-4-alkyl), —CO—NH—(C1-3-alkyl)-phenyl, —CO—NH—(C1-6-alkyl), —NH—(C1-6-alkyl), —NH—(C3-7-cycloalkyl), —NH—[(C1-3-alkyl)-(C3-7-cycloalkyl)] and NH—(C1-3-alkyl)-phenyl,wherein each alkyl and cycloalkyl is optionally substituted with one or more substituents selected from F and CF3; andwherein the hydrogen atom in each NH group is optionally replaced with C1-6-alkyl;or, if two R1-groups are attached to adjacent carbon atoms of the phenyl moiety of the tetrahydroisoquinolinyl group, they may be linked with each other and together form a C3-5-alkylene bridging group in which 1 or 2 —CH2-groups may independently of each other be replaced by —O—, —C(═O)—, —S—, —S(═O)—, —S(═O)2—, —NH— or —N(C1-4-alkyl)-; n is 0, 1, 2 or 3; R2 is selected from a group consisting of: H, C1-6-alkyl, C3-7-cycloalkyl, NH2, —NH—(C1-6-alkyl), —N(C1-6-alkyl)2, —O—(C1-6-alkyl), heterocyclyl, 5-membered heteroaryl containing 1 or 2 heteroatoms selected from O, S, N and NH, 6-membered heteroaryl containing one or two nitrogen atoms, and —(C1-3-alkyl)-(6-membered heteroaryl containing one or two nitrogen atoms); wherein each alkyl group is optionally substituted with one or more substituents selected from F, CN, CONH2, CONH(C1-3-alkyl), CON(C1-3-alkyl)2, NH2 and OH,wherein each cycloalkyl group is optionally substituted with one or more substituents selected from F, CN, OH, NH2, NH(CO)OC1-6-alkyl, C1-3-alkyl and CF3,wherein each heteroaryl group is optionally substituted with one or more substituents selected from F, Cl, C1-3-alkyl, NH2 and —NH—C(O)—(C1-3-alkyl), andwherein the heterocyclyl group is selected from a group consisting of 2-oxo-pyrrolidinyl, 2-oxo-dihydrofuranyl and morpholinyl; R3 is H or C1-4-alkyl; R4 is H or C1-4-alkyl; R5 is H or C1-3-alkyl; R6 is F, OH or —O—(C1-4-alkyl), or, if m is 2, both R6 groups together with the carbon atom, to which they are attached, may form a carbonyl group; and R7 is H, C1-4-alkyl, —COOH or —COO(C1-4-alkyl), and m is 0, 1 or 2;wherein each of the above-mentioned alkyl and —O-alkyl groups may be substituted by one or more F;or a pharmaceutically acceptable salt thereof.
地址 Ingelheim am Rhein DE