Use of physiological cooling active ingredients, and agents containing such active ingredients

A method for in-vitro or in-vivo modulation of the cold-menthol receptor TRPM8, wherein the receptor is brought into contact with one or more compounds of formula (I) or formula (II):

• wherein,
• R11, R12 and R13 independently of one another are selected from the group consisting of:
• H;
• linear or branched C1-C6-alkyl groups, optionally carrying 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen and linear or branched C1-C6-alkoxy groups;
• and linear or branched C1-C6-alkyloxy groups, optionally carrying 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen and linear or branched C1-C6-alkoxy groups;
• or
• R11 and R12 together with the carbon atoms to which they are bonded form a 4-, 5-, 6- or 7-membered, mono- or poly-unsaturated, carbo- or heterocyclic ring, which optionally carries 1, 2, 3, 4 or 5 identical or different substituents selected from the group consisting of linear or branched C1-C6-alkyl groups and oxo groups (═O), and the ring-heteroatoms are identical or different and are selected from the group consisting of O, N and S;
• X and Z independently of one another are selected from the group consisting of —O—, —S—, —NH—, —S(═O)—, and —S(═O)2— groups;
• and
• Y is a linear or branched C1-C8-alkylene group, which optionally carries 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen, and linear or branched C1-C6-alkoxy groups;
• or
• X-Y-Z together with the carbon atoms to which they are bonded form a keto group;
• and salts of these compounds and optionally in pure stereoisomer form or as a mixture of stereoisomers;
• wherein,
• R21 and R22 independently of one another are selected from the group consisting of:
• H;
• linear or branched C1-C6-alkyl groups, which optionally carry 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen, and linear or branched C1-C6-alkoxy groups;
• linear or branched C1-C6-alkyloxy groups, which optionally carry 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen and linear or branched C1-C6-alkoxy groups;
• mono- or polynuclear aryl-, arylalkyl- and heteroaryl groups, which optionally carry 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen, linear or branched C1-C6-alkyl groups and linear or branched C1-C6-alokoxy groups;
• wherein the heteroaryl groups have 1, 2, 3 or 4 ring-heteroatoms, which are identical or different and are selected from the group consisting of O, N and S;
• R23 is selected from among:
• H;
• linear or branched C1-C6-alkyl groups which optionally carry 1, 2, 3 or 4 identical or different substituents selected from among NH2, OH, SH, halogen, and linear or branched C1-C6-alkoxy groups;
• C3-C7-cycloalkyl groups, which optionally carry 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen, linear or branched C1-C6-alkyl groups, and linear or branched C1-C6-alkoxy groups;
• wherein the cycloalkyl group optionally is bonded via a C1-C4-alkylene group to Z;
• and wherein optionally 1, 2 or 3 ring carbon atoms can be replaced by identical or different heteroatoms, selected from the group consisting of O, N and S;
• mono- or polynuclear aryl-, arylalkyl- and heteroaryl groups, which optionally carry 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen, linear or branched C1-C6-alkyl groups, and linear or branched C1-C6-alokoxy groups;
• wherein the heteroaryl groups have 1, 2, 3 or 4 ring-heteroatoms, which are identical or different and are selected from the group consisting of O, N and S;
• X is O, S or methylene;
• Y is N or CH;
• and
• Z is O, S or NR24, wherein
• R24 stands for H;
• or a linear or branched C1-C6-alkyl group, which optionally carries 1, 2, 3 or 4 identical or different substituents selected from the group consisting of NH2, OH, SH, halogen and linear or branched C1-C6-alkoxy groups;
• or
• R24 and R23 together with the Z-group to which they are bonded form a 4-, 5-, 6- or 7-membered, saturated, or mono- or polyunsaturated heterocyclic ring, which optionally carries 1, 2, 3, 4 or 5 identical or different linear or branched C1-C6-alkyl groups, and which has 1, 2 or 3 additional ring-heteroatoms, which are identical or different and are selected from the group consisting of O, N and S;
• and salts of these compounds;
• optionally in pure stereoisomer form or as a mixture of to stereoisomers.