Phenyl and pyridinyl-1,2,4-oxadiazolone derivatives, processes for their preparation and their use as pharmaceutical compositions

A compound of formula I:

• wherein
• B is C(R4) or N;
• R1 is selected from the group consisting of H, halogen, (C1-C8)alkyl, (C1-C4) alkylene-O—(C1-C4)alkylene-H, (C1-C2)alkylene-O—(C1-C2)alkylene-(C3-C6)cycloalkyl, SCH3, and CN, wherein the alkyl and alkylene groups are optionally un-substituted or are mono, bi- or trisubstituted by F;
• R2, R3 and R4 are independently selected from the group consisting of H, halogen, (C1-C8)alkyl, (C1-C4)alkylene-O—(C1-C4)alkylene-H, SCH3 and CN, wherein the alkyl and alkylene groups are optionally un-substituted or are mono, bi- or trisubstituted by F;
• X is selected from the group consisting of O, S, S(O), S(O)2, O—CH2, S—CH2, CH2—O, and CH2—S;
• one of U or V is N and the other is S or O;
• W is selected from the group consisting of a bond, (C1-C8)alkylene, (C2-C8)alkenylene, (C1-C6)alkylene-(C3-C6)cycloalkylene, and (C3-C6) cycloalkylene-(C1-C6)alkylene, wherein the alkyl and alkylene groups are optionally un-substituted or are mono, bi- or trisubstituted by F;
• Y is selected from the group consisting of a bond, O, S, S(O), S(O)2, and N(R6) and
• R5 is selected from the group consisting of H, (C1-C8)alkyl, (C1-C4) alkylene-(C3-C13)cycloalkyl, (C1-C4)alkylene-(C6-C14)aryl, (C2-C8) alkenyl, (C1-C4)alkylene-(C3-C15)heterocycloalkyl, (C1-C4)alkylene-(C3-C15)heterocycloalkenyl, (C1-C4)alkylene-(C5-C15)heteroaryl, (C1-C4) alkylene-CO—(C1-C4)alkyl, (C1-C4)alkylene-CO—(C1-C4)alkylene-(C3-C13)cycloalkyl, (C1-C4)alkylene-CO—(C1-C4)alkylene-(C6-C10)aryl, (C1-C4)alkylene-CO—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, (C1-C4) alkylene-CO—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, (C1-C4) alkylene-CO—(C1-C4)alkylene-(C5-C15)heteroaryl, SO2(C1-C4)alkyl, SO2(C1-C4)alkylene-(C3-C13)cycloalkyl, SO2(C1-C4)alkylene-(C6-C10) aryl, SO2(C1-C4)alkylene-(C3-C15)heterocycloalkyl, SO2(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, SO2(C1-C4)alkylene-(C5-C15)heteroaryl, CO—O—(C1-C4)alkylene-(C6-C10)aryl, CO—O—(C1-C4)alkyl, CO—O—(C1-C4) alkylene-(C3-C13)cycloalkyl, CO—O—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, CO—O—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, CO—O—(C1-C4)alkylene-(C5-C15)heteroaryl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C6-C10)aryl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C13)cycloalkyl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, CO—N((C1-C4) alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, CO—N((C1-C4) alkylene-H)—(C1-C4)alkylene-(C5-C15)heteroaryl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C6-C10)aryl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C13)cycloalkyl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, and SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C5-C15)heteroaryl wherein alkyl and alkylene are un-substituted or mono-, di- or tri-substituted by F, S—(C1-C4)alkyl, SO—(C1-C4)alkyl, SO2(C1-C4) alkyl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, CO—O(C1-C4)alkyl, (C1-C4)alkyl and O—(C1-C4) alkylene-H and wherein cycloalkyl, aryl, heterocycloalkyl, heterocycloalkenyl and heteroaryl are un-substituted or mono-, di- or tri-substituted by F, Cl, Br, CF3, (C1-C4)alkyl and (C1-C4)-alkylen-O—(C1-C4)alkylene-H,
• with the proviso that if Y is S, S(O) or S(O)2
• R5 is selected from the group consisting of SO2(C1-C4)alkyl, SO2(C1-C4)alkylene-(C3-C13)cycloalkyl, SO2(C1-C4)alkylene-(C6C10)aryl, SO2(C1-C4)alkylene-(C3-C15)heterocycloalkyl, SO2(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, SO2(C1-C4)alkylene-(C5-C15)heteroaryl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C6-C10)aryl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, SO2N((C1-C4)alkylene-SH)—(C1-C4)alkylene-(C3-C13)cycloalkyl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C5-C15)heteroaryl;
• with the proviso that,
• if Y is a bond or O then
• Z is a bond;
• or
• Y is a bond, with the proviso that R5 is selected from the group consisting of CN, (C1-C8)alkyl mono-, di- or tri-substituted by F, CO—(C1-C4)alkyl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, SO2N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, N((C1-C4) alkylene-H)—CO—(C1-C4)alkylene-H, (C1-C6)alkylene-(C3-C13)cycloalkyl, (C3-C15) heterocycloalkyl, (C3-C15)heterocycloalkenyl, and (C5-C15)heteroaryl;
• or
• Y is O, with the proviso that R5 is selected from the group consisting of (C1-C8)alkyl mono-, di- or tri-substituted by F, CO—(C1-C4)alkyl, CO—O—(C1-C4)alkylene-(C6-C10) aryl, CO—O—(C1-C4)alkylene-(C3-C13)cycloalkyl, CO—O—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, CO—O—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, CO—O—(C1-C4)alkylene-(C5-C15)heteroaryl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C6-C10)aryl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C13)cycloalkyl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C13)cycloalkyl, CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C5-C15)heteroaryl, (C1-C4)alkylene-(C3-C13)cycloalkyl, (C1-C4)alkylene-(C3-C15)heterocycloalkyl, (C1-C4)alkylene-(C3-C15)heterocycloalkenyl, (C1-C4)alkylene-(C5-C15)heteroaryl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, (C1-C4)alkylene-N((C1-C4) alkylene-H)—(C1-C4)alkylene-(C3-C13)cycloalkyl, (C1-C4)alkylene-N((C1-C4) alkylene-H)—(C1-C4)alkylene-(C6-C10)aryl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, and (C1-C4)alkylene-N((C1-C4) alkylene-H)—(C1-C4)alkylene-(C5-C15)heteroaryl;
• R6 is selected from the group consisting of H, (C1-C8)alkyl, (C2-C8)alkenyl, and (C1-C4)alkylene-(C3-C6)cycloalkyl, wherein the alkyl and alkylene groups are optionally un-substituted or are mono, bi- or trisubstituted by F;
• R5 and R6 together with the nitrogen atom to which they are bonded (Y═N(R6)) form a (C3-C15)-heterocycloalkyl, a (C3-C15)-heterocycloalkenyl or a (C5-C15)-heteroaryl which can contain additionally 1 to 3 heteroatoms N, O, S in which further the heteroatoms can be oxidized and which is un-substituted or mono-, di- or tri-substituted by halogen, CN, CF3, (C1-C4)alkyl, (C1-C4)alkylene-(C3-C6)cycloalkyl, (C1-C4)alkylene-O—(C1-C4)alkylene-H, (C1-C4)alkylene-O—(C1-C4)alkylene-(C3-C6)cycloalkyl, (C1-C4)alkylene-O—(C1-C4)alkylene-(C6-C10)aryl, (C1-C4)alkylene-O—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, (C1-C4)alkylene-O—(C1-C4)alkylene-(C3-C15) heterocycloalkenyl, (C1-C4)alkylene-O—(C1-C4)alkylene-(C5-C15)heteroaryl, (C1-C4) alkylene-S—(C1-C4)alkyl, (C1-C4)alkylene-SO—(C1-C4)alkyl, (C1-C4)alkylene-SO2(C1-C4)alkyl, (C1-C4)alkylene-CO—(C1-C4)alkyl, (C1-C4)alkylene-CO—(C6-C10)aryl, (C1-C4)alkylene-CO—(C3-C15)heterocycloalkyl, (C1-C4)alkylene-CO—(C3-C15)heterocycloalkenyl, (C1-C4)alkylene-CO—(C5-C15)heteroaryl, (C1-C4)alkylene-CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-H, (C1-C4)alkylene-CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C6)cycloalkyl, (C1-C4)alkylene-CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C6-C10)aryl, (C1-C4)alkylene-CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, (C1-C4)alkylene-CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, (C1-C4)alkylene-CO—N((C1-C4)alkylene-H)—(C1-C4)alkylene-(C5-C15)heteroaryl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—CO—(C1-C4)alkyl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—CO—(C1-C4)alkylene-(C3-C6)cycloalkyl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—CO—(C1-C4)alkylene-(C6-C10)aryl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—CO—(C1-C4)alkylene-(C3-C15)heterocycloalkyl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—CO—(C1-C4)alkylene-(C3-C15)heterocycloalkenyl, (C1-C4)alkylene-N((C1-C4)alkylene-H)—CO—(C1-C4)alkylene-(C5-C15)heteroaryl, (C1-C4)alkylene-(C6-C14)aryl and (C1-C4) alkylene-(C3-C15)heterocycloalkyl, (C1-C4)alkylene-(C3-C15)heterocycloalkenyl, and (C1-C4)alkylene-(C5-C15)heteroaryl wherein heteroaryl, heterocycloalkyl and heterocycloalkenyl are optionally mono- or di-substituted by oxo residue and where alkyl is un-substituted or mono-, di- or tri-substituted by F;
• Z is selected from the group consisting of a bond, (C1-C8)alkylene, (C2-C8) alkenylene, (C2-C8)alkylidene and (C1-C6)alkylene-O—(C1-C6)alkylene;
• R7 and R8 are independently selected from the group consisting of H, halogen, (C1-C8)alkyl, (C1-C4)alkylene-O—(C1-C4)alkylene-H, SCF3, SF5, S(O)2CF3, (C1-C4)alkylene-O—(C6-C12)aryl, (C1-C4)alkylene(C6-C12)aryl, and NO2, wherein alkyl and alkylene are un-substituted or mono-, di- or tri-substituted by F and aryl is un-substituted or mono-, di- or tri-substituted by halogen, (C1-C4)alkyl or O—(C1-C4)alkyl ;
• its' stereoisomers, enantiomers, salts and mixtures thereof.