Bis-aromatic amides and their uses as sweet flavor modifiers, tastants, and taste enhancers

A method for increasing the sweet taste of a comestible or medicinal product comprising:

• (a) providing at least one comestible or medicinal product, or at least one precursor thereof, and
• (b) combining the at least one comestible or medicinal product or at least one precursor thereof with from about 0.01 to about 100 ppm of at least one bis-aromatic amide compound, or a comestibly acceptable salt thereof, and a sweet flavoring agent amount of sucrose, fructose, glucose, or a mixture thereof, so as to form a modified comestible or medicinal product;
• wherein the bis-aromatic amide compound has the structure:
• wherein
• (i) Ar1 and Ar2 are independently selected from phenyl, napthyl, indolyl, pyridyl, pyrimidyl, pyrrolyl, furanyl, thiofuranyl, quinolinyl, benzofuranyl, triazolyl, and benzothiofuranyl rings;
• (ii) m is selected from the integers 0, 1, 2, or 3;
• (iii) m′ is selected from the integers 0, 1, or 2;
• (iv) each R1 and R2 is independently selected from the group consisting of a hydroxy, fluoro, chloro, NH2, NO2, NHCH3, N(CH3)2, COOCH3, SCH3, SC2H5, methyl, ethyl, propyl, isopropyl, vinyl, allyl, S(O)CH3, S(O)2CH3, CN, CH2OH, C(O)H, C(O)CH3, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy radical;
• (v) R3 is a C1-C4 alkyl;
• (vi) R4 is hydrogen, or a C1-C4 alkyl;
• (vii) R5 is a C1-C10 normal or branched alkyl or cycloalkyl, wherein the normal or branched alkyl or cycloalkyl optionally comprises one to or two substituents independently selected from hydroxy, fluoro, chloro, NH2, NO2, NHCH3, N(CH3)2, COOCH3, SCH3, SC2H5, methyl, ethyl, propyl, isopropyl, vinyl, allyl, S(O)CH3, S(O)2CH3, CN, CH2OH, C(O)H, C(O)CH3, trifluoromethyl, methoxy, ethoxy, isopropoxy, and trifluoromethoxy radical;
• or a comestibly acceptable salt thereof.

A sweet comestible or medicinal product comprising from about 0.01 to about 100 ppm of at least one bis-aromatic amide compound, or a comestibly acceptable salt thereof, and at least a sweet flavoring agent amount of one or more natural, semi-synthetic, or synthetic sweet flavoring agents, or a mixture thereof;

• wherein the bis-aromatic amide compound has the structure:
• Wherein
• (i) Ar1 and Ar2 are independently selected from a phenyl, pyridyl, pyrimidyl, pyrazinyl, pyrrolyl, pyrazolyl, furanyl, thiofuranyl, triazolyl, isoxazolyl, oxadiazolyl, or indolyl ring;
• (ii) m and m′ are independently selected from the integers 0, 1, or 2;
• (iii) each R1 and R2 is independently selected from the group consisting of OH, NH2, NO2, SH, SO3H, PO3H, halogen, and a C1-C4 organic radical;
• (iv) R3 and R4 are independently selected from hydrogen and methyl,
• (v) R5 is a C3-C10 branched alkyl optionally comprising one, two, or three substituents independently selected from OH, NH2, a halogen, and a C1-C6 organic radical;
• or a comestibly acceptable salt thereof.

A bis-aromatic amide compound having the structure:

• wherein
• (i) Ar1 and Ar2 are independently selected from a phenyl or monocyclic heteroaryl rings;
• (ii) m and m′ are independently selected from the integers 0, 1, or 2;
• (iii) each R1 and R2 is independently selected from the group consisting of OH, NH2, NO2, SH, SO3H, PO3H, halogen, and a C1-C4 organic radical;
• (iv) R3 and R4 are independently selected from hydrogen and a C1-C4 alkyl,
• (v) R5 is a C3-C10 branched alkyl optionally comprising one, two, or three substituents independently selected from OH, NH2, a halogen, and a C1-C6 organic radical;
• or a comestibly acceptable salt thereof.

A compound having the formula:

• 2-(4-(6-cyanopyrazin-2-yl)phenyl)-N-isobutyl-2-methylpropanamide;
• 2-(4-(5-cyanopyridin-3-yl)phenyl)-2-methyl-N-(pentan-3-yl)propanamide;
• (R)-N-sec-butyl-2-(4-(5-cyanopyridin-3-yl)phenyl)-2-methylpropanamide;
• 2-(4-(5-cyanopyridin-3-yl)phenyl)-N-isobutyl-2-methylpropanamide;
• 2-methyl-N-(2-methylbutyl)-2-(4-(pyrimidin-5-yl)phenyl)propanamide;
• 2-(4-(5-(ethoxymethyl)pyridin-3-yl)phenyl)-N-isobutyl-2-methylpropanamide;
• N-isobutyl-2-(2-methoxy-3′-(methoxymethyl)biphenyl-4-yl)-2-methylpropanamide;
• N-isobutyl-2-(4-(6-(methoxymethyl)pyrazin-2-yl)phenyl)-2-methylpropanamide;
• N-isobutyl-2-(3′-(methoxymethyl)biphenyl-4-yl)-2-methylpropanamide;
• N-isobutyl-2-(4-(5-(methoxymethyl)pyridin-3-yl)phenyl)-2-methylpropanamide;
• N-isobutyl-2-methyl-2-(4-(1-methyl-1H-pyrrol-2-yl)phenyl)propanamide;
• 2-(2′-(hydroxymethyl)biphenyl-4-yl)-N-isobutyl-2-methylpropanamide;
• (S)-N-(1-hydroxybutan-2-yl)-2-(3′-(methoxymethyl)biphenyl -4-yl)-2-methylpropanamide;
• N-isobutyl -2-methyl-2-(4-(pyrimidin-5-yl)phenyl)propanamide;
• 2-(4-(6-cyanopyrazin-2-yl)phenyl)-N-(2-methoxypropyl)-2-methylpropanamide;
• (R)-N-sec-butyl-2-(4-(6-cyanopyrazin-2-yl)phenyl)-2-methylpropanamide;
• or a comestibly acceptable salt thereof.

A method for increasing the sweet taste of a comestible or medicinal product comprising:

• (a) providing at least one comestible or medicinal product, or at least one precursor thereof, and
• (b) combining the at least one comestible or medicinal product or at least one precursor thereof with at least a sweet flavor modulating amount of at least one bis-aromatic amide compound, or one or more comestibly acceptable salts thereof, so as to form a modified comestible or medicinal product;
• wherein the bis-aromatic amide compound has the structure:
• wherein
• (i) Ar1 and Ar2 are independently selected from monocyclic aryl, fused bicyclic aryl, monocyclic heteroaryl, or fused bicyclic heteroaryl rings;
• (ii) m is selected from the integers 0, 1, 2, 3, 4, or 5;
• (iii) m′ is selected from the integers 0, 1, 2, 3, or 4;
• (iv) each R1 and R2 is independently selected from the group consisting of an OH, NH2, NO2, SH, SO3H, PO3H, halogen, and a C1-C6 organic radical;
• (v) L is a carbon or nitrogen atom;
• (vi) R3 is hydrogen, oxygen, hydroxy, halogen, or a C1-C6 organic radical;
• (vii) R4 is absent, or hydrogen, oxygen, hydroxy, halogen, or a C1-C6 organic radical;
• (viii) R5 is a C1-C14 organic radical comprising a normal or branched alkyl or cycloalkyl, wherein the normal or branched alkyl or cycloalkyl optionally comprises one to four substituents independently selected from OH, NH2, NO2, SH, SO3H, PO3H, halogen, and a C1-C6 organic radical;
• or a comestibly acceptable salt thereof.