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US 10,584,134 B2Granted
Use of physiological cooling active ingredients, and agents containing such active ingredients
AssigneesSymrise AG, BASF SE
InventorsThomas Subkowski, Michael Backes, Heiko Oertling, Arnold Machinek, Hubert Loges, Ulrike Simchen, Horst Surburg, Claus Bollschweiler, Jens Wittenberg, Wolfgang Siegel
Life of this patent
Estimating the term…
Abstract
The invention relates to a TRPM8 modulator for achieving a cooling effect on the skin or a mucous membrane.
Claims17
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 (II):
- 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
- 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;
- wherein the one or more compounds having the structure represented by formula (II) do not have a structure represented by formula (IIa), provided below:
- and salts of these compounds;
- optionally in pure stereoisomer form or as a mixture of stereoisomers.
24 more elements
A pharmaceutical composition comprising one or more compounds having a structure represented by formula (II), as provided below, or salts thereof;
- 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-all yloxy 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
- X is O, S or methylene;
- Y is N or OH;
- 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;
- wherein the one or more compounds having the structure represented by formula (II) do not have a structure represented by formula (IIa), provided below:
23 more elements
Dependencies are inferred from the claim text.