# US 11,028,052 B2 · Compounds useful as modulators of TRPM8

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- Number: US 11,028,052 B2
- Document ID: US11028052B2
- Status: Granted
- Kind: B2
- Application number: 16/574,657
- Filed: 2019-09-18
- Published: 2020-01-09
- Granted: 2021-06-08
- Earliest claimed: 2013-02-19
- Assignees: Firmenich SA
- Applicants: Firmenich Incorporated
- Inventors: Lyudmyla Chumakova; Andrew Patron; Chad Priest; Donald Karanewsky; Rachel Kimmich; Brant Clayton Boren; Jeffrey Robert Hammaker; Volodymyr Chumakov; Wen Zhao; Alain Noncovich; Jane Ung
- Web page: https://patentgrep.com/patent/US11028052B2

## CPC

- C07D 231/20: One oxygen atom attached in position 3 or 5
- A23L 2/52: Adding ingredients (adding preservatives A23B70/10)
- A23L 33/10: using additives (addition of substantially indigestible substances A23L33/21)
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07C 233/31: with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by an acyclic carbon atom
- C07D 207/26: 2-Pyrrolidones
- C07D 207/32: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D 207/333: Radicals substituted by oxygen or sulfur atoms
- C07D 213/50: Ketonic radicals
- C07D 233/78: Radicals substituted by oxygen atoms
- C07D 235/02: condensed with carbocyclic rings or ring systems
- C07D 239/22: with hetero atoms directly attached to ring carbon atoms
- C07D 239/62: Barbituric acids
- C07D 333/22: Radicals substituted by doubly bound hetero atoms, or by two hetero atoms other than halogen singly bound to the same carbon atom
- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 403/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 405/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D 409/06: linked by a carbon chain containing only aliphatic carbon atoms
- A23V 2002/00: Food compositions, function of food ingredients or processes for food or foodstuffs
- C07C 2601/04: with a four-membered ring
- C07C 2601/14: The ring being saturated
- C07C 2601/16: the ring being unsaturated
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A23L: FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF (preservation thereof A23B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07C: ACYCLIC OR CARBOCYCLIC COMPOUNDS
- A23V: INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION

## Abstract

The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.

## Claims

### Claim 1

A compound having structural Formula (Ib):
or a salt or solvate thereof; wherein
R5 or R6 is selected from C1-C3 alkyl, and the remaining R5 or R6 is selected from the group consisting of optionally substituted C3-C8 cycloalkyl and optionally substituted C3-C8 cycloalkenyl;
X and X1 are N;
R7 is C1-C3 alkyl;
R8 is represented by (a) or (b):
A is O;
B is CH2, or C═O;
C is CH2, or C═O;
Ar and Ar1 are independently optionally substituted phenyl, or optionally substituted heteroaryl; and
R11 is selected from the group consisting of hydrogen or optionally substituted C1-C4 alkyl.

### Claim 2 (depends on 1)

A compound of claim 1, selected from the group consisting of:
or a salt or solvate thereof.

### Claim 3 (depends on 1)

The compound of claim 1, wherein the compound is
or a salt or solvate thereof.

### Claim 4 (depends on 1)

A composition comprising a compound of claim 1, or a salt or solvate thereof; and at least one carrier.

### Claim 5 (depends on 4)

The composition of claim 4, which is an ingestible composition or personal care composition.

### Claim 6 (depends on 5)

The composition of claim 5, wherein the ingestible composition is a food or beverage.

### Claim 7 (depends on 4)

The composition of claim 4, wherein the compound in the composition is in a concentration ranging from about 1 ppm to about 500 ppm.

### Claim 8 (depends on 4)

The composition of claim 4, which is a textile product or a packaging material.

### Claim 9 (depends on 5)

The composition of claim 5, wherein the composition is in the form of a solid, semisolid, plaster, solution, suspension, lotion, cream, foam, gel, paste, emulsion, or a combination thereof.

### Claim 10 (depends on 1)

The compound of claim 1 or a salt or solvate thereof for use in a method of modulating transient receptor potential channel melastatin member 8 (TRPM8).

### Claim 11 (depends on 1)

The compound of claim 1 or a salt or solvate thereof for use in either a) a method of modulating the cooling sensation of a composition, or b) a method of inducing a cooling sensation in a human or animal.

### Claim 12 (depends on 10)

The compound of claim 10 or a salt or solvate thereof, wherein the compound is a TRPM8 receptor agonist.