# US 2014/0194433 A1 · Detection and use of low molecular-weight modulators of the cold-menthol receptor trpm8 > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0194433 A1 - Document ID: US20140194433A1 - Status: Published application - Kind: A1 - Application number: 14/206,182 - Filed: 2014-03-12 - Published: 2014-07-10 - Earliest claimed: 2008-08-26 - Assignees: BASF SE - Inventors: Thomas Subkowski; Claus Bollschweiler; Jens Wittenberg; Michael Krohn; Holger Zinke - Web page: https://patentgrep.com/patent/US20140194433A1 ## CPC - C07D 495/22: in which the condensed system contains four or more hetero rings - A23L 27/88: {Taste or flavour enhancing agents} - A61K 8/42: Amides - A61K 8/49: containing heterocyclic compounds - A61K 8/4926: {having six membered rings} - A61K 8/4946: {Imidazoles or their condensed derivatives, e.g. benzimidazoles} - A61K 8/4953: {containing pyrimidine ring derivatives, e.g. minoxidil} - A61K 8/4973: {with oxygen as the only hetero atom} - A61K 8/69: containing fluorine - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/445: Non condensed piperidines, e.g. piperocaine - A61P 13/02: of urine or of the urinary tract, e.g. urine acidifiers - A61P 13/08: of the prostate - A61P 13/10: of the bladder - A61P 25/00: Drugs for disorders of the nervous system - A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] - A61P 33/00: Antiparasitic agents - A61P 35/00: Antineoplastic agents - A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 - A61Q 5/02: Preparations for cleaning the hair - A61Q 11/00: Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses - A61Q 17/02: containing insect repellants - A61Q 17/04: Topical preparations for affording protection against sunlight or other radiation; Topical sun tanning preparations - A61Q 19/004: {Aftersun preparations} - C07C 275/28: having nitrogen atoms of urea groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton - C07D 211/14: with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom - C07D 233/84: Sulfur atoms - C07D 241/44: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring - C07D 317/64: Oxygen atoms - C07D 401/04: directly linked by a ring-member-to-ring-member bond - C07D 401/12: linked by a chain containing hetero atoms as chain links - C07D 409/12: linked by a chain containing hetero atoms as chain links - C07D 495/20: Spiro-condensed systems - A61K 2800/244: Endothermic; Cooling; Cooling sensation - A61K 2800/78: Enzyme modulators, e.g. Enzyme agonists - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) - A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B) - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - A61Q: SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS - C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS ## Abstract The invention relates to novel modulators of the cold menthol receptor TRPM8, to a method for modulating the TRPM8 receptor using said modulators; to the use of the modulators for induction of cold sensation; and to objects and means produced using said modulators. ## Claims ### Claim 1 A method for the in-vitro or in-vivo modulation of the cold menthol receptor TRMP8, comprising contacting the receptor with at least one compound which is selected from polynuclear organic compounds which, in a cellular activity test using cells which recombinantly express the human TRPM8 receptor, modulate the permeability of these cells for Ca2+ ions. ### Claim 2 (depends on 1) The method according to claim 1, where the compound has at least two 4- to 7-membered rings which, independently of one another, are carbo- or heterocyclic, mono- or polycyclic, and wherein at least two of these rings can optionally be condensed. ### Claim 3 (depends on 1) The method according to claim 1, wherein the modulator has an agonistic or antagonistic effect on the cellular Ca2+ ion permeability. ### Claim 4 (depends on 1) The method according to claim 1, where the modulator is a compound selected from the compounds of the formulae 1 to 19: ### Claim 5 A modulator for the TRPM8 receptor which is selected from polynuclear organic compounds which, in a cellular activity test using a cell which recombinantly expresses the human TRPM8 receptor, modulates the permeability of the cell for Ca2+ ions. ### Claim 6 (depends on 5) The use of a modulator for the TRPM8 receptor according to claim 5 for inducing a sensation of coldness in humans and/or animals. ### Claim 7 (depends on 5) The use of a modulator for the TRPM8 receptor according to claim 5 as an active constituent of a pharmaceutical composition. ### Claim 8 (depends on 5) The use of a modulator for the TRPM8 receptor according to claim 5 for the treatment of prostate carcinomas, for the treatment of bladder weakness or in pain therapy. ### Claim 9 (depends on 5) The use of a modulator for the TRPM8 receptor according to claim 5 as insect repellent or insecticide. ### Claim 10 (depends on 5) The use of a modulator for the TRPM8 receptor according to claim 5 for inducing a sensation of coldness in a packaging. ### Claim 11 (depends on 5) The use of a modulator for the TRPM8 receptor according to claim 5 for inducing a sensation of coldness in a textile. ### Claim 12 (depends on 5) The modulator for the TRPM8 receptor according to claim 5 for use as mediator of the TRMP8 receptor. ### Claim 13 (depends on 5) A composition comprising at least one modulator for the TRPM8 receptor according to claim 5. ### Claim 14 (depends on 13) The composition according to claim 13, selected from a) pharmaceutical compositions, such as antitumor agents, agents for the treatment of diseases of the bladder, painkillers; b) foods, such as ice cream, mousse, cream, beverages, confectionery; c) mouthcare compositions, such as toothpaste, mouthwash, chewing gum; d) skincare or haircare compositions, such as suncream, sunburn cream, lotions, shampoos, plasters; and e) insect repellents, insecticides. ### Claim 15 (depends on 5) A textile product such as e.g. a shirt, trousers, socks, a towel, finished with at least one modulator for the TRPM8 receptor according to claim 5. ### Claim 16 (depends on 5) A packaging material which is associated with at least one modulator for the TRPM8 receptor according to claim 5.