Isosorbide derivatives and their use as flavor modifiers, tastants, and taste enhancers

1. A compound having structural formula (I)

or the salt, solvate, ester, or N-oxide thereof, wherein:

A is aryl, or heteroaryl, selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, furanyl, thiofuranyl, oxazoloyl, isoxazoloyl, thiazolyl, and triazole;

Y is hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, substituted carbocyclyl, acyl, halo, —CN, —NO 2 , —OR 1 , —S(O)R 1 , —S(O) 2 R 1 , —OC(O)R 1 , —N(R 1 )C(O)R 2 , —NR 1 R 2 , —C(O)NR 1 R 2 , —C(O)OR 1 , —S(O) 2 NR 1 R 2 , —COR 1 , —N(R 1 )S(O) 2 R 2 , —SR 1 , —C(R 1 R 2 R 6 ), —C(S)—R 1 , —C(═NR 2 )—R 1 , —N(R 1 )—C(═N—OR 2 )R 6 , —N(R 1 )C(S)NR 2 R 6 , —C(═N—OR 1 )R 2 , —C(═NR 1 )—NR 2 R 6 , —N(R 1 )C(═NR 2 )NR 6 R 7 , —N(R 1 )C(S)R 2 , —N(R 1 )—C(O)—C(O)R 2 , —C(S)—NR 1 R 2 , —N(R 1 )C(═NR 2 )OR 6 , —C(═NR 1 )O—NR 2 R 6 , —N(R 1 )N(R 2 )C(O)OR 6 , —N(R 1 )C(O)OR 2 , —N(R 1 )C(O)NR 2 R 6 , —N(R 1 )—C(O)—C(O)—NR 2 R 6 , —C(O)—C(O)—NR 1 R 2 , —P(O)(OR 1 )(OR 2 ), —P(O)(OR 1 )(R 2 ), or —P(O)R 1 R 2 ;

X is —O—, —S—, —S(O)—, —S(O) 2 —, —C(R 3 R 4 )—, —C(O)—, —C(S)—, —C(═NR 3 )—, —C(O)O—, —N(R 3 )—, —OC(O)—, —N(R 3 )C(O)—, —C(O)N(R 3 )—, —N(R 3 )—C(═N—OR 4 )—, —C(═N—OR 3 )—, —C(═NR 3 )—NR 4 —, —N(R 3 )C(S)N(R 4 )—R 5 , —N(R 3 )C(O)N(R 4 )—R 5 , —N(R 3 )C(═NR 4 )—, —N(R 3 )C(S)—, —N(R 3 )—C(O)—C(O)—, —C(S)—N(R 3 )—, —N(R 3 )S(O) 2 —, —S(O) 2 —N(R 3 )—, —N(R 3 )C(═NR 4 )O—, —C(═NR 4 )O—N(R 3 )—, —N(R 3 )—C(═NR 4 )—N(R 5 )—, —N(R 3 )N(R 4 )C(O)O—, —N(R 3 )C(O)O—, —N(R 3 )C(O)N(R 4 )—, —N(R 3 )—C(O)—C(O)—NR 4 —, —C(O)—C(O)—NR 4 —, —P(O)(OR 3 )—, or —P(O)R 3 —;

Z is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, or substituted carbocyclyl; and

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , and R 7 are each independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl; and

with the following proviso:

when A is triazole; then —X—Z is not —O-alkyl, —O-acyl, or sulfonamide.

2. The compound of claim 1 , wherein Y is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbocyclyl, or substituted carbocyclyl.

3. The compound of claim 1 , wherein:

A is monocyclic five-membered heteroaryl selected from the group consisting of pyrrolyl, furanyl, thiofuranyl, oxazoloyl, isoxazolyl, thiazolyl, and triazole;

Y is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl,heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl;

X is —O—, —S—, —S(O)—, —S(O) 2 —, —C(R 3 R 4 )—, —C(O)—, —C(S)—, —C(═NR 3 )—, —C(O)O—, —N(R 3 )—, —OC(O)—, —N(R 3 )C(O)—, —C(O)N(R 3 )—, —C(═N—OR 3 )—, —C(═NR 3 )—NR 4 —, —N(R 3 )C(═NR 4 )—, —N(R 3 )C(S)—, —C(S)—N(R 3 )—, —N(R 3 )S(O) 2 —, —S(O) 2 —N(R 3 )—, —N(R 3 )C(═NR 4 )O—, —C(═NR 4 )O—N(R 3 )—, —N(R 3 )—C(═NR 4 )—N( 5 )—, —N(R 3 )N(R 4 )C(O)O—, —N(R 3 )C(O)O—, —N(R 3 )C(O)N(R 4 )—, —NR 3 —C(O)—C(O)—NR 4 —, —C(O)—C(O)—NR 4 —, —P(O)(OR 3 )—, or —P(O)(R 3 )—;

Z is alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl; and

R 3 , R 4 , and R 5 are each independently hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, carbocyclyl, or substituted carbocyclyl.

4. A compound having structural formula (Ia):

or the salt, solvate, ester, or N-oxide thereof, wherein

X a is —S(O)—, —S(O) 2 —, —C(R 3 R 4 )—, —C(O)—, —C(O)O—, —C(O)N(R 3 )—, —C(═N—OR 3 )—, —C(═NR 3 )—NR 4 —, —C(═NR 3 )—, —C(S)—N(R 3 )—, —C(S)—, —NR 3 —C(O)—C(O)—NR 4 —, —C(O)—C(O)—NR 4 —, or —S(O) 2 —N(R 3 )—;

Y is alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbocyclyl, or substituted carbocyclyl;

Z is alkyl, substituted alkyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, heteroarylalkyl, substituted heteroarylalkyl, heterocyclylalkyl, substituted heterocyclylalkyl, carbocyclyl, or substituted carbocyclyl; and

R hydrogen, alkyl, or substituted alkyl.

5. A compound having a structural formula selected from the group consisting of

or the salt, solvate, ester, or N-oxide thereof.

6. A composition comprising a compound having structural formula (I) of claim 1 ,

or the salt, solvate, ester, or N-oxide thereof; and a carrier.

7. The composition of claim 6 , which comprises an ingestible composition.

8. A method for modulating the savory taste of a composition comprising combining the composition with at least one compound of formula (I) according to claim 1 .

9. A food or beverage product comprising a compound of formula (I) according to claim 1 .

10. A compound of the following structural formula (I):

or a salt, solvate, ester, or N-oxide thereof,

wherein

A is a covalent bond;

Y is -N(R 1 )C(O)R 2 , —NR 1 R 2 , —C(O)NR 1 R 2 , —N(R 1 )S(O) 2 R 2 , —N(R 1 )—C(═N—OR 2 )R 6 , —C(═N—OR 1 )R 2 , —C(═NR 1 )—NR 2 R 6 , 13 N(R 1 )C(═NR 2 )R 6 , 13 N(R 1 )C(S)R 2 , —N(R 1 )—C(O)—C(O)R 2 , —N(R 1 )C(S)N(R 2 )—R 6 , —C(S)—NR 1 R 2 , —N(R 1 )C(═NR 2 )OR 6 , —C(═NR 1 )O—NR 2 R 6 , —N(R 1 )—C(═NR 2 )—N(R 6 )R 7 , —N(R 1 )N(R 2 )C(O)OR 6 —N(R 1 )C(O)OR 2 , —N(R 1 )C(O)NR 2 R 6 , or —N(R 1 )—C(O)—C(O)—NR 2 R 6 ;

X is —N(R 3 )C(O)—, —N(R 3 )—, —N(R 3 )S(O) 2 —, —N(R 3 )—C(═N—OR 4 )—, —N(R 3 )C(═NR 4 )—, —N(R 1 )—C(═NR 2 )—N(R 6 )—, —N(R 3 )C(S)—, —N(R 3 )C(S)N(R 4 )—, —N(R 3 )C(O)N(R 4 )—, —N(R 3 )C(═NR 4 )O—, —N(R 3 )—C(═NR 4 )—N(R 5 )—, —N(R 3 )N(R 4 )C(O)O—, or —N(R 3 )C(O)O—;

Z is aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkyl, substituted arylalkyl, heteroarylalkyl, substituted heteroarylalkyl, carbocyclyl, or substituted carbocyclyl; and

R 1 , R 2 , R 6 and R 7 are each independently alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkylnyl, heteroalkyl, substituted heteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, arylalkenyl, substituted arylalkenyl, heteroaryl, substituted heteroaryl, heterocyclyl, substituted heterocyclyl, carbocyclyl, substituted carbocyclyl, heteroarylalkyl, or substituted heteroarylalkyl.

11. The compound of claim 10 , wherein Z is carbocyclyl or substituted carbocyclyl.

12. A ingestible composition comprising a compound of formula (I) of claim 10 , or the salt, solvate, ester, or N-oxide thereof.

13. The ingestible composition of claim 12 , which is a food or beverage.

14. A method for modulating the savory taste of a composition comprising combining the composition with at least one compound of formula (I) according to claim 10 .