Tetrahydropyran and thiopyran derivatives having multimodal activity against pain

Compound of Formula (I):

• wherein
• R1 is
• m is 1, 2 or 3;
• n is 0, 1 or 2;
• p is 0, 1 or 2;
• q is 0 or 1;
• W is nitrogen or carbon;
• X is a bond, —C(RxRx′)—, C═O or —O—;
• wherein Rx is selected from the group consisting of halogen, —OR7, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
• Rx′ is selected from the group consisting of hydrogen, halogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
• R7 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
• Y is —S— or —O—;
• R1′ is selected from the group consisting of substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;
• wherein the cycloalkyl, aryl or heterocyclyl in R1′, if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R11, —OR11, —NO2, —NR11R11′″, NR11C(O)R11, —NR11S(O)2R11, —S(O)2NR11R11, —NR11C(O)NR11′R11″, —SR11, —S(O)R11, S(O)2R11, —CN, haloalkyl, haloalkoxy, —C(O)OR11, —C(O)NR11R11′, —OCH2CH2OH, —NR11S(O)2NR11′R11″ and C(CH3)2OR11;
• additionally, the cycloalkyl or non-aromatic heterocyclyl in R1′, if substituted, may also be substituted with
• or ═O;
• wherein the alkyl, alkenyl or alkynyl in R1′, if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR11, halogen, —CN, haloalkyl, haloalkoxy, —SR11, —S(O)R11, and —S(O)2R11;
• wherein R11, R11′ and R11″ are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl;
• and wherein R11′″, is selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl and -Boc;
• R2 is selected from the group consisting of substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl,
• wherein the cycloalkyl, aryl or heterocyclyl in R2, if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R12, —OR12, —NO2, —NR12R12′″, —NR12C(O)R12′, —NR12S(O)2R12′, —S(O)2NR12R12′, —NR12C(O)NR12′R12″, —SR12, —S(O)R12, —S(O)2R12, —CN, haloalkyl, haloalkoxy, —C(O)OR12, —C(O)NR12R12′, —OCH2CH2OH, —NR12S(O)2NR12′R12″ and —C(CH3)2OR12;
• additionally, the cycloalkyl or non-aromatic heterocyclyl in R2, if substituted, may also be substituted with
• or ═O;
• wherein the alkyl, alkenyl or alkynyl in R2, if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR12, halogen, —CN, haloalkyl, haloalkoxy, —SR12, —S(O)R12, and —S(O)2R12;
• wherein R12, R12′ and R12″ are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl;
• and wherein R12′″ is selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl and -Boc;
• R3 and R3′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
• R4 and R4′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl,
• alternatively, R4 and R4′, together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;
• R4″ and R4′″ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl,
• alternatively, R4″ and R4′″, together with the carbon atom to which they are attached, form a substituted or unsubstituted cycloalkyl;
• R5 and R5′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl, substituted or unsubstituted C2-6 alkynyl, —CHOR8 and —C(O)OR8;
• wherein R8 is selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
• R6 and R6′ are independently selected from the group consisting of hydrogen, —OR9, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
• wherein R9 and R9′ are independently selected from the group consisting of hydrogen, substituted or unsubstituted C1-6 alkyl, substituted or unsubstituted C2-6 alkenyl and substituted or unsubstituted C2-6 alkynyl;
• and wherein
• is selected from the group consisting of
• wherein Rn is selected from the group consisting of unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl and unsubstituted C2-6 alkynyl;
• the alkyl, alkenyl or alkynyl, other than those defined in R1′ or R2, if substituted, is substituted with one or more substituent/s selected from the group consisting of —OR13, halogen, —CN, haloalkyl, haloalkoxy, —SR13, —S(O)R13, and —S(O)2R13;
• wherein R13, and R13 are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, and unsubstituted C2-6 alkynyl;
• the aryl, heterocyclyl or cycloalkyl other than those defined in R1′ or R2, if substituted, is substituted with one or more substituent/s selected from the group consisting of halogen, —R14, —OR14, —NO2, —NR14R14′″, NR14C(O)R14′, —NR14S(O)2R14′, —S(O)2NR14R14′, —NR14C(O)NR14′R14″, —SR14, —S(O)R14, S(O)2R14, —CN, haloalkyl, haloalkoxy, —C(O)OR14, —C(O)NR14R14′, —OCH2CH2OH, —NR14S(O)2NR14′R14″ and C(CH3)2OR14;
• additionally, wherein the cycloalkyl or non-aromatic heterocyclyl, other than those defined in R1′ or R2, if substituted, may also be substituted with
• or ═O;
• wherein R14, R14′ and R14″ are independently selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;
• and wherein R14′″ is selected from the group consisting of hydrogen, unsubstituted C1-6 alkyl, unsubstituted C2-6 alkenyl, unsubstituted C2-6 alkynyl and -Boc;
• optionally as a stereoisomer, including enantiomers and diastereomers, a racemate or as a mixture of at two of stereoisomers, including enantiomers and/or diastereomers, in any mixing ratio, or a corresponding salt thereof, or a corresponding solvate thereof;
• wherein the following compound is excluded:
• and the following compound is excluded: