Substituted condensed pyrimidine compounds

摘要

The invention relates to novel substituted condensed pyrimidine compounds of general formula (I);
in which the chemical groupings, substituents and indices are as defined in the description, and to their use as medicaments, in particular as medicaments for the treatment of conditions and diseases that can be treated by inhibition of the PDE4 enzyme.

主权项

1. A pyrimidine compound of formula (I): in which
G is selected from the following groups G1 to G47:in which the site marked with an asterisk (*) indicates the binding site at position 2 of the pyrimidine ring;
Z independently of one another is (C1-C6) alkyl, (C1-C6) hydroxyalkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, —S(C1-C6) alkyl, halogen, hydroxyl or cyano or is SO2(C1-C6)alkyl, CONH2,NHSO2(C1-C6)alkyl, NHCO(C1-C6)alkyl wherein the aforementioned alkyls are branched or straight-chain and is optionally substituted; T is CR1R2 or S(O)X or S(O)═NH; x is 0, 1 or 2; R1 and R2 independently of one another are hydrogen, (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, halogen, hydroxyl or cyano, wherein the aforementioned alkyl chains are branched or straight-chain and is optionally substituted; n is 1 or 2; K is (C1-C6) alkyl, (C1-C6) alkoxy, (C1-C6) haloalkyl, halogen, hydroxyl or cyano, wherein the aforementioned alkyl chains are branched or straight-chain and is optionally substituted; m is 0, 1, 2, 3 or 4; X independently of one another is (C1-C6) alkyl, (C3-C6) cycloalkyl, (C1-C6) alkoxy, (C3-C6) cycloalkoxy, (C1-C6) haloalkyl, (C1-C6) haloalkoxy, halogen, hydroxyl, cyano, carboxyl, C(O)—NH2, C(O)—NH(C1-C6)alkyl, C(O)—N((C1-C6) alkyl)2, NH2, NH(C1-C6)alkyl, N((C1-C6) alkyl)2, N-pyrrolidinyl, N-piperidinyl, N-morpholinyl, NH—CHO, NH—C(O)—(C1-C6)alkyl, S(O)2—NH2, S(C1-C6)alkyl, S(O)—(C1-C6)alkyl, S(O)2—(C1-C6)alkyl, O—(C1-C4)alkyl-CN, O—(C1-C4)alkyl-NH —CHO, O—(C1-C4)alkyl-NH—C(O)—(C1-C6)alkyl, or O—(C1-C4) alkyl-N((C1-C6) alkyl)2, or is O—(C1-C4)alkyl-O—(C1-C4)alkyl, wherein the aforementioned alkyl chains are branched or straight-chain and is optionally substituted, or is a chemical grouping L—CO2R3 or O—(C1-C4)alkyl-CO—R4 or LCONR4 ; R3 is hydrogen, branched or straight-chain (C1-C6)alkyl; R4 is NH2, NHR5, NR5R6, (C1-C6) alkoxy; R5 and R6 independently of one another is (C1-C6) alkyl, (C1-C6) hydroxyalkyl, (C3-C6) cycloalkyl, (C1-C6)alkyl(C3-C6)cycloalkyl, (C3-C6) heterocycloalkyl, or R5 and R6, together with the nitrogen atom to which they are bound form a saturated 3- to 6-membered heterocycle, optionally substituted with branched or straight-chain (C1-C6) alkyl or hydroxyl groups, which heterocycle can optionally have at least one further heteroatom selected from O, S, and N; L is a bond, (C1-C6) alkylene, (C2-C6) alkenylene, —O—(C1-C4) alkylene, —NH—(C1-C4) alkylene, or -NR3—(C1-C4) alkylene, wherein aforementioned alkylenes or alkenylenes can each be substituted with one or more halogen atoms or wherein aforementioned alkylenes or alkenylenes is optionally substituted with one or more (C1-C6) alkyl groups, or wherein in aforementioned alkylenes or alkenylenes a CH2 unit is optionally replaced by an oxygen atom; p is 1, 2, 3 or 4; U˜V is selected from CR7R8—CR7R8; CR7═CR7, N═CR7, CR7═N, N═N, C(═O)—CR7R8, and C(═O)—O; and R7 and R8 independently of one another are hydrogen, (C1-C4) alkyl, (C1-C4) alkoxy, CHF, CH2F or CF3, (C1-C4) hydroxyalkyl, F, Cl, Br, hydroxyl or cyano; or a pharmacologically tolerable salt, diastereomer, enantiomer, racemate, hydrate or solvate thereof.