Compounds reducing malodour perception and the use thereof

A process for the preparation of a compound of formula (I)

• comprising the steps of:
• (a) coupling a compound of a formula A with a compound of formula B, thereby obtaining a compound of formula C, and
• (b1) contacting compound of formula C with phosphorane derivatives D thereby obtaining compound of formula (I);
• or (b2) contacting compound of formula C phosphonate derivative F thereby obtaining compound of formula (I);
• wherein
• X is selected from the group consisting of —C(═O)OR8, cyano, —C(═O)—C1-6alkyl, —C(═O)—NR9R10, hydroxyC1-6alkyl, —C(═O)H, and C1-6alkoxyC1-6alkyl;
• R1 is hydrogen or C1-6alkyl;
• R2 is hydrogen or a group selected from C1-7alkyl and C2-7alkenyl, each group being optionally substituted with one or more C3-6cycloalkyl;
• R3 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R4 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R5 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R6 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R7 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R8 is hydrogen or C1-6alkyl;
• R9 is hydrogen or C1-6alkyl;
• R10 is hydrogen or C1-6alkyl;
• R11 is C6-12aryl or C1-12alkyl;
• and
• R12 is C1-12alkyl.

An in-vitro method for identifying compounds that antagonize the response of the OR7D4 olfactory receptor to androstenone comprising the steps of:

• contacting at least one cell, or membrane thereof, expressing the nucleic acid sequence encoding OR7D4, with androstenone and at least one test compound of formula (I), and
• measuring the effect of at least one test compound(s) on the response of OR7D4 to androstenone;
• wherein
• X is selected from the group consisting of —C(═O)OR8, cyano, —C(═O)—C1-6alkyl, —C(═O)—NR9R10, hydroxyC1-6alkyl, —C(═O)H, and C1-6alkoxyC1-6alkyl;
• R1 is hydrogen or C1-6alkyl;
• R2 is hydrogen or a group selected from C1-7alkyl and C2-7alkenyl, each group being optionally substituted with one or more C3-6cycloalkyl;
• R3 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R4 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R5 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R6 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R7 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R8 is hydrogen or C1-6alkyl;
• R9 is hydrogen or C1-6alkyl;
• and R10 is hydrogen or C1-6alkyl.

A method for reducing or eliminating the olfactory perception of androstenone or another OR7D4 activator, comprising the step of using a compound of formula (I) to reduce or eliminate the olfactory perception of androstenone or another OR7D4 activator;

• wherein
• X is selected from the group consisting of —C(═O)OR8, cyano, —C(═O)—C1-6alkyl, —C(═O)—NR9R10, hydroxyC1-6alkyl, —C(═O)H, and C1-6alkoxyC1-6alkyl;
• R1 is hydrogen or C1-6alkyl;
• R2 is hydrogen or a group selected from C1-7alkyl and C2-7alkenyl, each group being optionally substituted with one or more C3-6cycloalkyl;
• R3 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R4 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R5 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R6 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R7 is selected from the group consisting of hydrogen, halo, C1-6alkyl, C1-6alkoxy, C1-6alkoxyC1-6alkyl, and cyano;
• R8 is hydrogen or C1-6alkyl;
• R9 is hydrogen or C1-6alkyl;
• and R10 is hydrogen or C1-6alkyl.