Substituted thiophenes: compositions, processes of making, and uses in disease treatment and diagnosis

A compound of formula I, a pharmaceutically acceptable salt of said compound of formula I, or a trifluoroacetic acid salt of said compound of formula I:

• 85
• in which:
• R1 and R2
• are independently selected from the group consisting of H, F, Cl, Br, I, CN, NO2, —(X)n—CqH2q—Z, cycloalkyl having 3, 4, 5 or 6 carbon atoms, alkenyl having 2, 3 or 4 carbon atoms, alkenylalkyl having 3 or 4 carbon atoms, and ethynyl or alkylalkynyl having 3 or 4 carbon atoms, wherein
• n is zero or 1;
• X is oxygen, NH, N—CH3, or S(O)k, wherein k is zero, 1 or 2;
• q is zero, 1, 2, 3, 4, 5 or 6;
• and
• Z is hydrogen or CmF2m+1, wherein m is zero, 1, 2, 3 or 4;
• R3 is hydrogen, methyl, F, Cl, Br, I, CN, S(O)k—CH3, —NO2, or —O—CH3, wherein
• k is zero, 1 or 2;
• R4 is hydrogen, cycloalkyl having 3, 4, 5, or 6 carbon atoms, alkenyl having 2, 3 or 4 carbon atoms, alkenylalkyl having 3 or 4 carbon atoms, ethynyl or alkylalkynyl having 3 or 4 carbon atoms, or —CrH2r—Y, wherein
• r is zero, 1, 2, 3 or 4;
• and
• Y is hydrogen or trifluoromethyl;
• R5 and R6 are hydrogen atoms or are together a bond;
• R7 and R8
• are independently selected from the group consisting of (C3-C5)-alkyl, (C2-C5)-alkenyl, (C2-C5)-alkynyl, (C3-C6)-cycloalkyl and (C4-C6)-cycloalkenyl;
• or
• R7 and R8
• together with the two carbon atoms to which R7 and R8 are attached, form a (C5-C10) cycloalkenyl ring which may be unsubstituted or substituted with one or more fluorine atoms;
• or
• R7 and R8
• together with the two carbon atoms to which R7 and R8 are attached, form a ring of the following formula;
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• wherein
• R10 and R11
• are independently selected from the group consisting of hydrogen, fluorine, chlorine, bromine, methyl, CN, OH, —O—CH3, NO2, NH2 and —CF3;
• R9 and R12 are hydrogen or F;
• or
• R9 is hydrogen and R12 is selected from the group consisting of F, Cl, Br, I, CN, NO2, COOH, CO—NR13R14, SO2—NR13R14, alkenyl having 2, 3 or 4 carbon atoms, alkenylalkyl having 3 or 4 carbon atoms, ethynyl, alkylalkynyl having 3 or 4 carbon atoms, and —(X)n—CqH2q—Z;
• or R12 is hydrogen and R9 is selected from the group consisting of F, Cl, Br, I, CN, NO2, COOH, CO—NR13R14, SO2—NR13R14, alkenyl having 2, 3 or 4 carbon atoms, alkenylalkyl having 3 or 4 carbon atoms, ethynyl, alkylalkynyl having 3 or 4 carbon atoms, and —(X)n—CqH2q—Z;
• wherein:
• R13 is hydrogen oralkyl having 1, 2, 3 or 4 carbon atoms and R14 is hydrogen or alkyl having 1, 2, 3, or 4 carbon atoms;
• or
• R13 and R14 together with the nitrogen to which they are attached form a saturated 5-, 6- or 7-membered ring;
• n is zero or 1;
• X is oxygen, NH, N—CH3, S(O)k;
• k is zero, 1 or 2;
• q is zero, 1, 2, 3, 4, 5 or 6;
• and
• Z is hydrogen or CmF2m+1, wherein m is zero, 1, 2, 3 or 4.