Malonamide derivatives

A compound of formula

• wherein
• R1 is selected from
• R2 is lower alkyl, lower alkinyl, —(CH2)n—O-lower alkyl, —(CH2)n—S-lower alkyl, —(CH2)n—CN, —(CR′R″)n—CF3, —(CR′R″)n—CHF2, —(CH2)n—C(O)O-lower alkyl, —(CH2)n-halogen, or is —(CH2)n-cycloalkyl optionally substituted by one or more substituents selected from the group consisting of phenyl, halogen and CF3;
• R′,R″ are each independently hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy;
• R3, R4 are each independently hydrogen, lower alkyl, phenyl or halogen;
• R5 is lower alkyl or —(CH)2-cycloalkyl;
• R6 is hydrogen or halogen;
• R7 is hydrogen or lower alkyl;
• R8 is hydrogen, lower alkyl, lower alkinyl or —(CH)2-cycloalkyl;
• R9 is hydrogen, lower alkyl, —C(O)-lower alkyl, —C(O)-lower cycloalkyl, —(CH2)n-cycloalkyl, phenyl, —C(O)-phenyl optionally substituted by one or more substituents selected from the group consisting of halogen and —C(O)O-lower alkyl, or is (CH)2-phenyl optionally substituted by halogen;
• n is 0, 1, 2, 3 or 4;
• or a pharmaceutically acceptable acid addition salt, optically pure enantiommer, racemate or diastereomeric mixture thereof.

A composition comprising a compound of formula I

• wherein
• R1 is selected from
• R2 is lower alkyl, lower alkinyl, —(CH2)n—O-lower alkyl, —(CH2)n—S-lower alkyl, —(CH2)n—CN, —(CR′R″)n—CF3, —(CR′R″)n—CHF2, —(CR′R″)n—CH2F, —(CH2)n—C(O)O-lower alkyl, —(CH2)n-halogen, or is —(CH2)n-cycloalkyl optionally substituted by one or more substituents selected from the group consisting of phenyl, halogen and CF3;
• R′,R″ are each independently hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy;
• R3, R4 are each independently hydrogen, lower alkyl, lower alkoxy, phenyl or halogen;
• R5 is hydrogen, lower alkyl, —(CH2)n—CF3 or —(CH2)n-cycloalkyl;
• R6 is hydrogen or halogen;
• R7 is hydrogen or lower alkyl;
• R8 is hydrogen, lower alkyl, lower alkinyl, —(CH2)n—CF3, —(CH2)n-cycloalkyl or —(CH2)n-phenyl optionally substituted by halogen;
• R9 is hydrogen, lower alkyl, —C(O)H, —C(O)-lower alkyl, —C(O)—CF3, —C(O)—CH2F, —C(O)—CHF2, —C(O)-cycloalkyl, —C(O)—(CH2)n—O-lower alkyl, —C(O)O—(CH2)n-cycloalkyl, —C(O)-phenyl optionally substituted by one or more substituents selected from the group consisting of halogen and —C(O)O-lower alkyl, or is —S(O)2-lower alkyl, —S(O)2—CF3, —(CH2)n-cycloalkyl or is —(CH2)n— phenyl optionally substituted by halogen;
• n is 0, 1, 2, 3 or 4;
• or a pharmaceutically acceptable acid addition salt, optically pure enantiommer, racemate or diastereomeric mixture thereof and a pharmaceutically acceptable carrier.

A composition comprising a compound of formula

• wherein
• R1 is selected from
• R2 is lower alkyl, lower alkinyl, —(CH2)n—O-lower alkyl, —(CH2)n—S-lower alkyl, —(CH2)n—CN, —(CR′R″)n—CF3, —(CR′R″)n—CHF2, —(CH2)n—C(O)O-lower alkyl, —(CH2)n-halogen, or is —(CH2)n-cycloalkyl optionally substituted by one or more substituents selected from the group consisting of phenyl, halogen and CF3;
• R′,R″ are each independently hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy;
• R3, R4 are each independently hydrogen, lower alkyl, phenyl or halogen;
• R5 is lower alkyl or —(CH)2-cycloalkyl;
• R6 is hydrogen or halogen;
• R7 is hydrogen or lower alkyl;
• R8 is hydrogen, lower alkyl, lower alkinyl or —(CH)2-cycloalkyl;
• R9 is hydrogen, lower alkyl, —C(O)-lower alkyl, —C(O)-lower cycloalkyl, —(CH2)n-cycloalkyl, phenyl, —C(O)-phenyl optionally substituted by one or more substituents selected from the group consisting of halogen and —C(O)O-lower alkyl, or is (CH)2-phenyl optionally substituted by halogen;
• n is 0, 1, 2, 3 or 4;
• or a pharmaceutically acceptable acid addition salt, optically pure enantiomer, racemate or diastereomeric mixture thereof and a pharmaceutically acceptable carrier.

A process for preparing a compound of formula

• wherein
• R1 is selected from
• R2 is lower alkyl, lower alkinyl, —(CH2)n—O-lower alkyl, —(CH2)n—S-lower alkyl, —(CH2)n—CN, —(CR′R″)n—CF3, —(CR′R″)n—CHF2, —(CR′R″)n—CH2F, —(CH2)n—C(O)O-lower alkyl, —(CH2)n-halogen, or is —(CH2)n-cycloalkyl optionally substituted by one or more substituents selected from the group consisting of phenyl, halogen and CF3;
• R′,R″ are each independently hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy;
• R3, R4 are each independently hydrogen, lower alkyl, lower alkoxy, phenyl or halogen;
• R5 is hydrogen, lower alkyl, —(CH2)n—CF3 or —(CH2)n-cycloalkyl;
• R6 is hydrogen or halogen;
• R7 is hydrogen or lower alkyl;
• R8 is hydrogen, lower alkyl, lower alkinyl, —(CH2)n—CF3, —(CH2)n-cycloalkyl or —(CH2)n-phenyl optionally substituted by halogen;
• R9 is hydrogen, lower alkyl, —C(O)H, —C(O)-lower alkyl, —C(O)—CF3, —C(O)—CH2F, —C(O)—CHF2, —C(O)-cycloalkyl, —C(O)—(CH2)n—O-lower alkyl, —C(O)O—(CH2)n-cycloalkyl, —C(O)-phenyl optionally substituted by one or more substituents selected from the group consisting of halogen and —C(O)O-lower alkyl, or is —S(O)2-lower alkyl, —S(O)2—CF3, —(CH2)n-cycloalkyl or is —(CH2)n— phenyl optionally substituted by halogen;
• and
• n is 0, 1, 2, 3 or 4;
• which process comprises
• reacting a compound of formula
• with a compound of formula
• NH2R2 III
• to produce a compound of formula

A method of treating Alzheimer's disease comprising administering to a patient having Alzheimer's disease a therapeutically effective amount of a compound of formula

• wherein
• R1 is selected from
• R2 is lower alkyl, lower alkinyl, —(CH2)n—O-lower alkyl, —(CH2)n—S-lower alkyl, —(CH2)n—CN, —(CR′R″)n—CF3, —(CR′R″)n—CHF2, —(CR′R″), —CH2F, —(CH2)n—C(O)O-lower alkyl, —(CH2)n-halogen, or is —(CH2)n-cycloalkyl optionally substituted by one or more substituents selected from the group consisting of phenyl, halogen and CF3;
• R′,R″ are each independently hydrogen, lower alkyl, lower alkoxy, halogen or hydroxy;
• R3, R4 are each independently hydrogen, lower alkyl, lower alkoxy, phenyl or halogen;
• R5 is hydrogen, lower alkyl, —(CH2)n—CF3 or —(CH2)n-cycloalkyl;
• R6 is hydrogen or halogen;
• R7 is hydrogen or lower alkyl;
• R8 is hydrogen, lower alkyl, lower alkinyl, —(CH2)n—CF3, —(CH2)n-cycloalkyl or —(CH2)n-phenyl optionally substituted by halogen;
• R9 is hydrogen, lower alkyl, —C(O)H, —C(O)-lower alkyl, —C(O)—CF3, —C(O)—CH2F, —C(O)—CHF2, —C(O)-cycloalkyl, —C(O)—(CH2)n—O-lower alkyl, —C(O)O—(CH2)n-cycloalkyl, —C(O)-phenyl optionally substituted by one or more substituents selected from the group consisting of halogen and —C(O)O-lower alkyl, or is —S(O)2-lower alkyl, —S(O)2—CF3, —(CH2)n-cycloalkyl or is —(CH2)n— phenyl optionally substituted by halogen;
• n is 0, 1, 2, 3 or 4;
• or a pharmaceutically acceptable acid addition salt, optically pure enantiomer, racemate or diastereomeric mixture thereof.