Phenyl derivatives, their manufacture and use as pharmaceutical agents

A pharmaceutical composition which comprises a compound of the formula

• and enantiomers and pharmaceutically acceptable salts and esters thereof, wherein
• X1 is O, S, CH2
• R1 is hydrogen or C1-7-alkyl;
• R2 is hydrogen or C1-7-alkyl, or, if X1 is CH2, R2 is hydrogen, C1-7-alkyl or C1-7-alkoxy;
• R3 is hydrogen or C1-7-alkyl;
• R4 and R8 independently from each other are selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl, halogen, C1-7-alkoxy-C1-7-alkyl, C2-7-alkenyl, C2-7-alkinyl, fluoro-C1-7-alkyl, cyano-C1-7-alkyl or cyano;
• R5, R6 and R7 independently from each other are selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl, halogen, C1-7-alkoxy-C1-7-alkyl, C2-7-alkenyl, C2-7-alkinyl, fluoro-C1-7-alkyl, cyano-C1-7-alkyl or cyano;
• and one of R5, R6 and R7 is
• wherein
• X2 is selected from the group consisting of S, O, NR9, (CH2)pNR9CO, or (CH2)pCONR9,
• R9 is selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl, fluoro-C1-7-alkyl, hydroxy-C2-7-alkyl, or C1-7-alkoxy-C2-7-alkyl;
• Y1, Y2, Y3 and Y4 are N or C—R12, and 1 or 2 of Y1, Y2, Y3 and Y4 are N and the other ones are
• R10 is C1-7-alkyl, C3-7-cycloalkyl, fluoro-C1-7-alkyl, or C1-7-alkoxy-C1-7-alkyl;
• R11 is hydrogen, C1-7-alkyl, C1-7-alkoxy-C1-7-alkyl;
• R12 independently from each other in each occurance is selected from the group consisting of hydrogen, C1-7-alkyl, C3-7-cycloalkyl, fluoro-C1-7-aklyl, C1-7-alkoxy-C1-7-alkyl, hydroxy-C1-7-alkyl, C1-7-alkylthio-C1-7-alkyl, carboxy-C1-7-alkoxy-C1-7-alkyl, carboxy, carboxy-C1-7-alkyl, mono- or di-C1-7-alkyl-amino-C1-7-alkyl, C1-7-alkanoyl-C1-7-alkyl, C2-7-alkenyl, and C2-7-alkinyl;
• R13 is aryl or heteroaryl;
• m is 0 or 1, n is 0, 1, 2 or 3, and p is 0, 1 or 2, and the sum of m, n and p is 1, 2, 3 or 4;
• provided that compounds of formula I are excluded, wherein
• X1 is O, R2 and R3 are hydrogen,
• R6 is equal to
• X2 is O or S, and m is 0 together with a pharmaceutically acceptable carrier or excipient.