WHAT IS CLAIMED IS:
`
`-55-
`
`A method of inhibiting a taste modulating protein,
`
`the method comprising
`
`contacting the taste modulating protein with a compound of Formula I:
`
`.
`
`R1
`/
`N
`
`l
`
`/>7Ar3
`N
`
`1
`
`1
`
`Ar
`
`A?
`
`or a pharmaceutically acceptable salt thereof; wherein:
`
`R1 is hydrogen, unsubstituted alkyl, or unsubstituted arylalkyl;
`
`Ar] and Ar2 are independently phenyl or heteroaryl, either of which is optionally
`
`substituted; and
`
`Ar3 is phenyl or a heteroaryl, either of which is optionally substituted.
`
`The method of claim 1, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl,
`
`pyrazinyl, and triazinyl, any of which is optionally substituted.
`
`The method of claim 1, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of unsubstituted phenyl, methylphenyl, methoxyphenyl,
`
`halophenyl, cyanophenyl, carboxyphenyl, aminophenyl, and hydroxyphenyl.
`
`The method of claim 1, wherein Ar1 and Ar2 are both unsubstituted phenyl.
`
`The method of claim 1, wherein Ar1 and Ar2 are both unsubstituted: C-attached
`
`pyridyl, C-attached pyridazinyl, C-attached pyrimidinyl, C-attached pyrazinyl,
`
`C-attached triazinyl, or an N-OXide thereof.
`
`The method of claim 1, wherein Ar3 is selected from the group consisting of
`
`phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl,
`
`any of which is optionally substituted.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-55-
`
`A method of inhibiting a taste modulating protein,
`
`the method comprising
`
`contacting the taste modulating protein with a compound of Formula I:
`
`.
`
`R1
`/
`N
`
`l
`
`/>7Ar3
`N
`
`1
`
`1
`
`Ar
`
`A?
`
`or a pharmaceutically acceptable salt thereof; wherein:
`
`R1 is hydrogen, unsubstituted alkyl, or unsubstituted arylalkyl;
`
`Ar] and Ar2 are independently phenyl or heteroaryl, either of which is optionally
`
`substituted; and
`
`Ar3 is phenyl or a heteroaryl, either of which is optionally substituted.
`
`The method of claim 1, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl,
`
`pyrazinyl, and triazinyl, any of which is optionally substituted.
`
`The method of claim 1, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of unsubstituted phenyl, methylphenyl, methoxyphenyl,
`
`halophenyl, cyanophenyl, carboxyphenyl, aminophenyl, and hydroxyphenyl.
`
`The method of claim 1, wherein Ar1 and Ar2 are both unsubstituted phenyl.
`
`The method of claim 1, wherein Ar1 and Ar2 are both unsubstituted: C-attached
`
`pyridyl, C-attached pyridazinyl, C-attached pyrimidinyl, C-attached pyrazinyl,
`
`C-attached triazinyl, or an N-OXide thereof.
`
`The method of claim 1, wherein Ar3 is selected from the group consisting of
`
`phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl,
`
`any of which is optionally substituted.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-56-
`
`The method of claim 1, wherein Ar3 is phenyl, pyrid-Z-yl, pyrid-3—y1, pyrid-4—y1,
`
`pyridazin—3—yl, pyridazin-4-yl, pyrimidin—Z—yl, pyrimidin-4-yl, pyrimidin-S-yl,
`
`pyrazin-Z-yl, 1,2,3-triazin—4-yl, 1,2,3-triazin—5-yl, or 1,3,5—triazin-2-yl, any of
`
`which is optionally substituted.
`
`The method of claim 1, wherein Ar3 is an unsubstituted: C-attached pyridyl,
`
`C—attached pyridazinyl, C-attached pyrimidinyl, C—attached pyrazinyl, C-attached
`
`triazinyl, or an N—oxide thereof.
`
`The method of claim 1, wherein Ar3 is selected from the group consisting of
`
`phenyl, C-attached pyridyl, C-attached pyrimidyl, and C—attached pyridazinyl, any
`
`of which is optionally substituted with one or more nitro, halo, cyano, carboxyl,
`
`amino, hydroxyl, alkyl, and cyanoalkyl substituents in any one or more of the
`
`ortho-, meta-, and para—positions.
`
`10.
`
`The method of claim 1, wherein
`
`R1 is hydrogen, unsubstituted C1-4 alkyl, or unsubstituted ary1(C1-4)alkyl;
`
`Ar1 and Ar2 are both unsubstituted phenyl;
`
`Ar3 is phenyl, substituted by one to three substituents independently selected from
`
`the group consisting of carboxy, alkoxycarbonyl, hydroxy, hydroxyalkyl, amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, and nitro.
`
`11.
`
`The method of claim 10, wherein Ar3 is phenyl, substituted in the para—position
`
`by
`
`one
`
`carboxy,
`
`alkoxycarbonyl,
`
`hydroxyalkyl,
`
`hydroxy,
`
`amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, or nitro.
`
`12.
`
`The method of claim 1, wherein the compound of Formula I is one of:
`
`methyl4—(4,5-diphenyl—1H—imidazol-2—yl)benzoate;
`
`[4-(4,5-diphenyl-1H-imidazol-2-y1)pheny1]methanol;
`
`4—(4,5—diphenyl-1H—imidazol—2—yl)aniline;
`
`4-(4,5—diphenyl-IH-imidazol-Z-yl)phenol;
`
`methy14—(4,5—diphenyl—1H—imidazol—2—y1)phenylcarbamate;
`
`Atty. Dkt. No. 2305.0330001/TJS/A—L
`
`
`
`-57-
`
`N-[4-(4,5—dipheny1—1H—imidazol—2—yl)phenyl]acetamide;
`
`4-(4,5—dipheny1—1H—imidazol-2-yl)benzonitrile;
`
`N—[4—(4,5—dipheny1-1H-imidazol—Z-yl)benzyl]methanesulfonamide;
`
`4-(4,5—dipheny1—1H—imidazol—2—y1)benzoic acid; and
`
`2-(4-nitro-phenyl)—4, 5-dipheny1— lH—imidazole;
`
`or a pharmaceutically acceptable salt thereof.
`
`13.
`
`14.
`
`15.
`
`16.
`
`17.
`
`18.
`
`19.
`
`20.
`
`The method of claim 1, wherein the taste modulating protein is a non-human
`
`TRPMS protein.
`
`The method of claim 13, wherein the taste modulating protein is a cow, horse,
`
`sheep, pig, chicken, turkey, quail, cat, dog, mouse, rat, rabbit, monkey, or guinea
`
`pig TRPMS protein.
`
`The method of claim 1, wherein the taste modulating protein is a human TRPMS
`
`protein.
`
`The method of claim 1, wherein the taste modulating protein is in vitro.
`
`The method of claim 1, wherein the compound of Formula I is administered as a
`
`pharmaceutical composition-
`
`The method of claim 17, wherein the compound of Formula I is administered in a
`
`concentration of about 0.01% to about 50%, by weight, of the pharmaceutical
`
`composition.
`
`The method of claim 1, wherein the compound of Formula I is administered as a
`
`veterinary composition.
`
`The method of claim 19, wherein the compound of Formula I is administered in a
`
`concentration of about 0.01% to about 50%, by weight, of the veterinary
`
`composition.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-58-
`
`21.
`
`22.
`
`23.
`
`24.
`
`25.
`
`‘ 26.
`
`27.
`
`28.
`
`29.
`
`The method of claim 1, wherein the compound of Formula I is administered as a
`
`food composition.
`
`The method of claim 21, wherein the compound of Formula I is administered in a
`
`concentration of about 0.01% to about 50%, by weight, of the food composition.
`
`The method of claim 1, wherein the compound of Formula I is administered as a
`
`cosmetic composition.
`
`The method of claim 23, wherein the compound of Formula I is administered in a
`
`concentration of about 0.01% to about 50%, by weight, of the cosmetic
`
`composition.
`
`The method of claim 1, wherein the compound of Formula I is administered as a
`
`dental hygienic composition.
`
`The method of claim 23, wherein the compound of Formula I is administered in a
`
`concentration of about 0.01% to about 50%, by weight, of the dental hygienic
`
`composition.
`
`The method of claim 1, wherein the compound of Formula I is administered in an
`
`amount of about 0.01 mg to about 100 mg.
`
`The method of claim 1, wherein the compound of Formula I is administered in an
`
`amount sufficient to inhibit the taste-modulating protein by about 10% to about
`
`95%.
`
`A method of masking a taste, the method comprising administering to a subject in
`
`need of taste-masking one or more compounds of Formula I:
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-59-
`
`Ar1
`
`Ar2
`
`l
`
`R1
`N/
`/>7Ar3
`N
`
`1
`
`or a pharmaceutically acceptable salt thereof; wherein:
`
`R1 is hydrogen, unsubstituted alkyl, or unsubstituted arylalkyl;
`
`Ar1 and Ar2 are independently phenyl or heteroaryl, either of which is optionally
`
`substituted; and
`
`AI3 is phenyl or a heteroaryl, either of which is optionally substituted.
`
`30.
`
`The method of claim 29, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidiny],
`
`pyrazinyl, and triazinyl, any of which is optionally substituted.
`
`31.
`
`The method of claim 29, wherein Ar1 and Ar2 are independently selected fi‘om the
`
`group
`
`consisting of unsubstituted phenyl, methylphenyl, methoxyphenyl,
`
`halophenyl, cyanophenyl, carboxyphenyl, aminophenyl, and hydroxyphenyl.
`
`32.
`
`33.
`
`The method of claim 29, wherein Ar1 and Ar2 are both unsubstituted phenyl.
`
`The method of claim 29, wherein Ar‘ and Ar2 are both C-attached pyridyl, 0-
`
`attached pyridazinyl, C-attached pyrimidinyl, C—attached pyrazinyl, C-attached
`
`triazinyl, or an N-oxide thereof.
`
`34.
`
`The method of claim 29, wherein Ar3 is selected from the group consisting of
`
`phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl,
`
`any of which is optionally substituted.
`
`-
`
`35.
`
`The method of claim 29, wherein Ar3 is phenyl, pyrid-2-yl, pyrid—3-y1, pyrid-4-yl,
`
`pyridazin-3—yl, pyridazin-4-yl, pyrimidin-Z-yl, pyrimidin-4-y1, pyrimidin-S-yl,
`
`pyrazin-Z-yl, 1,2,3—triazin-4—yl, 1,2,3-triazin-5-yl, or 1,3,5-triazin-2-yl,
`
`any of
`
`which is optionally substituted.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-60-
`
`36.
`
`The method of claim 29, wherein Ar3 is an unubstituted: C-attached pyridyl,
`
`C-attached pyridazinyl, C-attached pyrimidinyl, C-attached pyrazinyl, C-attached
`
`triazinyl, or an N—oxide thereof.
`
`37.
`
`The method of claim 29, wherein Ar3 is selected from the group consisting of
`
`phenyl, C-attached pyridyl, C-attached pyrimidyl, and C attached pyridazinyl, any
`
`of which is optionally substituted with one or more nitro, halo, cyano, carboxyl,
`
`amino, hydroxyl, alkyl, and cyanoalkyl substituents in any one of the ortho-,
`
`meta-, and para-positions.
`
`38.
`
`The method of claim 29, wherein:
`
`39.
`
`40.
`
`R1 is hydrogen, unubstituted CM alkyl, or unubstituted ary1(C1.4)alky1;
`
`Ar1 and Ar2 are both unsubstituted phenyl;
`
`Ar3 is phenyl, substituted by one to three substituents independently selected from
`
`the group consisting of carboxy,’ alkoxycarbonyl, hydroxy, hydroxyalkyl, amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, and nitro.
`
`The method of claim 38, wherein Ar3 is phenyl, substituted in the para-position
`
`by
`
`one
`
`carboxy,
`
`alkoxycarbonyl,
`
`hydroxyalkyl,
`
`hydroxy,
`
`amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, or nitro.
`
`The method of claim 29, wherein the compound of Formula I is one of:
`
`methyl4-(4,5 —diphenyl-IH-imidazol-2—yl)b enzoate;
`
`-
`
`[4-(4, 5—diphenyl- I H-imidazol-Z-yl)phenyl]methanol;
`
`4-(4,5-diphenyl—1H—imidazol—2—yl)aniline;
`
`4—(4,5—diphenyl-1H-imidazol—2—yl)phenol;
`
`methyl4-(4,5—dipheny1-1H—imidazol-2-y1)phenylcarbamate;
`
`N—[4-(4,5-diphenyl-1H-imidazol-2—yl)phenyl]acetamide;
`
`4—(4,5-diphenyl-IH—imidazol-2-y1)benzonitrile;
`
`N-[4-(4,5-diphenyl-1H-imidazol-2-yl)benzyl]methanesulfonamide;
`
`4—(4,5—diphenyl-1H-imidazol-2-yl)benzoic acid; and
`
`Atty. Dkt. N0. 2305 .033 OOOI/TJS/A-L
`
`
`
`41.
`
`42.
`
`43.
`
`44.
`
`45.
`
`46.
`
`47.
`
`48.
`
`49.
`
`-61-
`
`2—(4—nitro-phenyl)-4,5-dipheny1-lH-imidazole;
`
`or a pharmaceutically acceptable salt thereof.
`
`The method of claim 29, wherein the subject is human.
`
`The method of claim 29, wherein the taste in need of masking is a bitter taste.
`
`The method of claim 29, wherein the compound of Formula I is administered in
`
`an amount of about 0.01 mg to about 100 mg.
`
`The method of claim 29, wherein the compound of Formula I is administered in
`
`an amount sufficient to mask the taste by about 10% to about 95%.
`
`The method of claim 29, further comprising administering a composition having a‘
`
`taste in need of masking to a subject.
`
`The method of claim 45, wherein the composition having a taste in need of
`
`masking is a pharmaceutical, veterinary,
`
`food, cosmetic, or dental hygienic
`
`composition.
`
`The method of claim 46, wherein the compound of Formula I is present in the
`
`pharmaceutical, veterinary, food, cosmetic, or dental hygienic composition having
`
`a taste in need of masking.
`
`The method of claim 47, wherein the compound of Formula I is present in the
`
`pharmaceutical, veterinary, food, cosmetic, or dental hygienic composition having
`
`a taste in need of masking in an amout of about 0.01 mg to about 100 mg.
`
`The method of claim 48, wherein the compound of Formula I is present in the
`
`pharmaceutical, veterinary, food, cosmetic, or dental hygienic composition having
`
`a taste in need of masking in an amount of about 0.01% to about 50%, by weight,
`
`of the pharmaceutical, veterinary, food, cosmetic, or dental hygienic composition.
`
`Atty. Dkt. N0. 2305.0330001/TJS/A-L
`
`
`
`-62-
`
`50.
`
`51.
`
`52.
`
`53.
`
`The method of claim 48, wherein the compound of Formula I is present in the
`
`pharmaceutical, veterinary, food, cosmetic, or dental hygienic composition having
`
`a taste in need of masking in an amount sufficient to mask the taste of the
`
`pharmaceutical, veterinary, food, cosmetic, or dental hygienic composition by
`
`about 10% to about 95%.
`
`The method of claim 46, wherein the composition having a taste in need of
`
`masking is a pharmaceutical composition.
`
`The method of claim 51, wherein the pharmaceutical composition having a taste
`
`in need of masking contains a biologically active agent other than a compound of
`
`Formula I.
`
`The method of claim 52, wherein the biologically active agent is selected from the
`group consisting of analgesics, anesthetics, anorexiants, I appetite depressants,
`
`antacidics,
`
`antiasthmatics,
`
`antidiuretics,
`
`antipyretics,
`
`antihistamines,
`
`anticholinergics,
`
`antidiarrheals,
`
`antitussives,
`
`antinauseants,
`
`antiarrhythmics,
`
`antimicrobials, antibacterials, antifungals, antivirals, anti—inflammatory agents,
`
`agents active against
`
`flatulence, antimigraine agents, beta—receptor blockers,
`
`bronchodilators,
`
`psychopharmacological
`
`agents,
`
`spasmolytics,
`
`sedatives,
`
`antihyperkinetics,
`
`tranquilizers, decongestants, demulcents, agents for alcohol
`
`withdrawal,
`
`antitussives,
`
`fluorine supplements,
`
`laxatives,
`
`local
`
`antibiotics,
`
`corticosteroid supplements, agents against goiter formation, antiepileptics, agents
`
`against dehydration, antiseptics, NSAIDs, Hz—receptor antagonists, nutritional
`
`supplements, gastrointestinal active agents, alkaloids, supplements for
`
`trace
`
`elements,
`
`ion-exchange resins, cholesterol-depressant agents,
`
`lipid—lowering
`
`agents, expectorants, and combinations thereof.
`
`54.
`
`A method of inhibiting the depolarization of a taste receptor cell, comprising
`
`contacting the taste receptor cell with one or more compounds of Formula I:
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-53-
`
`R1
`/
`N
`
`l
`
`/>—Ar3
`N
`
`1
`
`1
`
`Ar
`
`Ar2
`
`or a pharmaceutically acceptable salt-thereof; wherein:
`
`R1 is hydrogen, unsubstituted alkyl, or unsubstituted arylalkyl;
`
`Ar1 and Ar2 are independently phenyl or heteroaryl, either of which is optionally
`
`substituted; and
`
`Ar3 is phenyl or a heteroaryl, either of which is optionally substituted.
`
`55.
`
`The method of claim 54, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl,
`
`pyrazinyl, and triazinyl, any of which is optionally substituted.
`
`56.
`
`The method of claim 54, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of unsubstituted phenyl, methylphenyl, methoxyphenyl,
`
`halophenyl, cyanophenyl, carboxyphenyl, aminophenyl, and hydroxyphenyl.
`
`57.
`
`58.
`
`The method of claim 54, wherein Ar1 and Ar2 are both unsubstituted phenyl.
`
`The method of claim 54, wherein Ar1 and Ar2 are both unubstituted: C-attached
`
`pyridyl, C—attached pyridazinyl, C—attached pyrimidinyl, C-attached pyrazinyl,
`
`C-attached triazinyl, or an N-oxide thereof.
`
`59.
`
`The method of claim 54, wherein AI3 is selected from the group consisting of
`
`phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl,
`
`any of which is optionally substituted.
`
`60.
`
`The method of claim 54, wherein Ar3 is phenyl, pyrid—2—yl, pyrid—3-yl, pyrid-4—yl,
`
`pyridazin-3-yl, pyridazin-4-yl, pyrimidin—Z-yl, pyrimidin-4-yl, pyrimidin-S-yl,
`
`pyrazin-Z-yl, 1,2,3—triazin-4-yl, 1,2,3-triazin-5-yl, or 1,3,5-triazin-2-yl,
`
`any of
`
`which is optionally substituted.
`
`Atty. Dkt. N0. 2305.0330001/TJS/A-L
`
`
`
`-64—
`
`61.
`
`The method of claim 54, wherein Ar3 is an unubstituted: C-attached pyridyl,
`
`C—attached pyridazinyl, C-attached pyrimidinyl,_ C—attached pyrazinyl, C—attached
`
`triazinyl, or an N—oxide thereof.
`
`62.
`
`The method of claim 54, wherein Ar3 is selected from the group consisting of
`
`phenyl, C-attached pyridyl, C-attached pyrimidyl, and C attached pyridazinyl, any
`
`of which is optionally substituted with one or more nitro, halo, cyano, carboxyl,
`
`amino, hydroxyl, alkyl, and cyanoalkyl substituents in any one or more of the
`
`ortho-, meta-, and para-positions.
`
`63.
`
`The method of claim 54, wherein:
`
`R1 is hydrogen, unsubstituted C14 alkyl, or unsubstituted aryl(CM)alkyl;
`
`Ar1 and Ar2 are both unsubstituted phenyl;
`
`Ar3 is phenyl, substituted by one to three substituents independently selected from
`
`the group consisting of carboxy, alkoxycarbonyl, hydroxy, hydroxyalkyl, amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, and nitro.
`
`64.
`
`The method of claim 63, wherein AI3 is phenyl, substituted in the para—position
`
`by
`
`one
`
`carboxy,
`
`alkoxycarbonyl,
`
`hydroxyalkyl,
`
`hydroxy,
`
`amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, or nitro.
`
`65.
`
`The method of claim 54, wherein the compound of Formula I is one of:
`
`methy14-(4,5-diphenyl-1H—imidazol-2-yl)benzoate;
`
`[4-(4,5-dipheny1-IH-imidazol-Z-y1)pheny1]methanol;
`
`4-(4,5-dipheny1-1H—imidazol-2-yl)aniline;
`
`4-(4,5-diphenyl-IH—imidazol-Z-y1)phenol;
`
`methy14-(4,5-diphenyl-1H-imidazo1-2—yl)phenylcarbamate;
`
`N-[4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl]acetamide;
`
`4-(4,5-diphenyl-IH—imidazol-2-y1)benzonitrile;
`
`N—[4-(4,5—diphenyl-IH-imidazol-Z-yl)benzy1]methanesulfonamide;
`
`4-(4,5-dipheny1-1H-imidazol-2-yl)benzoic acid; and
`
`Atty. Dkt. No. 2305.033 0001/TJS/A—L
`
`
`
`-65—
`
`2—(4-nitro—phenyl)-4,5-dipheny1—1H—imidazole;
`
`or a pharmaceutically acceptable salt thereof.
`
`66.
`
`67.
`
`68.
`
`69.
`
`70.
`
`71.
`
`72.
`
`The method of claim 54, wherein the taste receptor cell is human.
`
`The method of claim 54, wherein the compound of Formula I is administered as a
`
`pharmaceutical, veterinary, food, cosmetic, or dental hygienic composition.
`
`The method of claim 67, wherein the compound of Fonnula I is administered in a
`
`concentration of about 0.01% to about 50%, by weight, of the pharmaceutical,
`
`veterinary, food, cosmetic, or dental hygienic composition.
`
`The method of claim 54, wherein the compound of Formula I is administered in
`
`an amount of about 0.01 mg to about 100 mg.
`
`The method of claim 54, wherein the compound of Formula I is administered in
`
`an amount sufficient to inhibit the depolarization of the taste-receptor cell by
`
`about 10% to about 95%.
`
`The method of claim 54, wherein the taste receptor cell can sense a taste produced
`
`by a biologically active agent.
`
`The method of claim 71, wherein the taste receptor cell can sense a taste produced
`
`by a biologically active agent selected from the group consisting of analgesics,
`
`anesthetics,
`
`anorexiants,
`
`appetite depressants,
`
`antacidics,
`
`antiasthmatics,
`
`antidiuretics,
`
`antipyretics,
`
`antihistamines,
`
`anticholinergics,
`
`antidiarrheals,
`
`antitussives,
`
`antinauseants,
`
`antiarrhythmics,
`
`antimicrobials,
`
`antibacterials,
`
`antifungals, antivirals, anti-inflammatory agents, agents active against flatulence,
`
`antimigraine
`agents,
`psychopharmacological
`
`beta-receptor
`agents,
`spasmolytics,‘
`
`blockers,
`sedatives,
`
`bronchodilators,
`antihyperkinetics,
`
`tranquilizers,
`
`decongestants,
`
`demulcents,
`
`agents
`
`for
`
`alcohol withdrawal,
`
`antitussives,
`
`fluorine supplements,
`
`laxatives,
`
`local antibiotics, corticosteroid
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-66-
`
`supplements, agents against goiter
`
`formation, antiepileptics, agents against
`
`dehydration,
`
`antiseptics, NSAIDs, Hz-receptor
`
`antagonists,
`
`nutritional
`
`supplements, gastrointestinal active agents, alkaloids, supplements for
`
`trace .
`
`elements,
`
`ion—exchange
`
`resins,
`
`cholesterol—depressant agents,
`
`lipid-lowering
`
`agents, expectorants, and combinations thereof.
`
`73.
`
`74.
`
`The method of claim 54, wherein the taste receptor cell can sense a bitter taste.
`
`A method of decreasing the palatability of food in a subject,
`
`the method
`
`comprising administering to a subject in need of such treatment one or more
`
`compounds of Fonnula I:
`
`R1
`/
`N
`
`l
`
`/>'Ar3
`N
`
`1
`
`1
`
`Ar
`
`Ar2
`
`or a pharmaceutically acceptable salt thereof; wherein:
`
`R1 is hydrogen, unsubstituted alkyl, or unsubstituted arylalkyl;
`
`Ar1 and Ar2 are independently phenyl or heteroaryl, either of which is optionally
`
`substituted; and
`
`Ar3 is phenyl or a heteroaryl, either of which is optionally substituted.
`
`‘75.
`
`The method of claim 74, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl,
`
`pyrazinyl, and triazinyl, any of which is optionally substituted.
`
`76.
`
`The method of claim 74, wherein Ar1 and Ar2 are independently selected from the
`
`group consisting of unsubstituted phenyl, methylphenyl, methoxyphenyl,
`
`halophenyl, cyanophenyl, carboxyphenyl, aminophenyl, and hydroxyphenyl.
`
`77.
`
`The method of claim 74, wherein Ar1 and Ar2 are both unsubstituted phenyl.
`
`Atty. Dkt. No. 2305.0330001/TJS/A—L
`
`
`
`-67..
`
`78.
`
`The method of claim 74, wherein Ar1 and Ar2 are both unubstituted: C-attached
`
`pyridyl, C-attached pyridazinyl, C-attached pyrimidinyl, C-attached pyrazinyl, C-
`
`attached triazinyl, or an N-oxide thereof.
`
`79.
`
`The method of claim 74, wherein Ar3 is selected from the group consisting of
`
`phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl,
`
`any of which is optionally substituted.
`
`80.
`
`The method of claim 74, wherein Ar3 is phenyl, pyrid-2-yl, pyrid-3—yl, pyrid-4-yl,
`
`pyridazin-3—yl, pyridazin-4—yl, pyrimidin—Z-yl, pyrimidin—4-y1, pyrin’iidin-S-yl,
`
`pyrazin-Z—yl, 1,2,3—triazin—4—yl, 1,2,3-triazin-5-yl, or 1,3,5-triazin-2-yl, any of
`
`which is optionally substituted.
`
`81.
`
`The method of claim 74, wherein Ar3 is an unubstituted: C—attached pyridyl,
`
`C—attached pyridazinyl, C-attached pyrimidinyl, C-attached pyrazinyl, C-attached
`
`triazinyl, or an N—oxide thereof.
`
`82.
`
`The method of claim 74, wherein Ar3 is selected from the group consisting of
`
`phenyl, C-attached pyridyl, C-attached pyrimidyl, and C-attached pyridazinyl, any
`
`of which is optionally substituted with one or more nitro, halo, cyano, carboxyl,
`
`amino, hydroxyl, alkyl, and cyanoalkyl substituents in any one or more of the
`
`ortho-, meta-, and para-positions.
`
`83.
`
`The method of claim 74, wherein:
`
`R1 is hydrogen, unsubstituted C14 alkyl, or unsubstituted ary1(C1-4)alkyl;
`
`ArI and Ar2 are both unsubstituted phenyl;
`
`Ar3 is phenyl, substituted by one to three substituents independently selected from
`
`the group consisting of carboxy, alkoxycarbonyl, hydroxy, hydroxyalkyl, amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, and nitro.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-68-
`
`84.
`
`The method of claim 83, wherein Ar3 is phenyl, substituted in the para—position
`
`by
`a
`carboxy,
`alkoxycarbonyl,
`hydroxyalkyl,
`hydroxy,
`5
`alkoxycarbonylamino, cyano, alkylsulfonylaminoallcyl, or nitro.
`
`amino,
`
`85.
`
`The method of claim 74, wherein the compound of Formula I is one of:
`
`methyl4-(4,5-diphenyl-1H-imidazol-2-y1)benzoate;
`
`[4-(4,5-dipheny1-1H—imidazol—Z—yl)pheny1]methanol;
`
`4-(4,5-diphenyl-IH-imidazol-2-yl)aniline;
`
`4-(4,5-dipheny1-1H—imidazol-2—yl)phenol;
`
`methy14—(4,5—diphenyl—IH—imidazol—Z—y1)phenylcarbamate;
`
`N—[4-(4,5—diphenyl-IH—imidazol-2-y1)phenyl]acetamide;
`
`4-(4,5-diphenyl-1H-imidazol-2-yl)benzonitrile;
`
`N-[4-(4,5-dipheny1-IH-imidazol-Z-yl)benzyl]methanesulfonamide;
`
`4—(4,5-diphenyl-1H—imidazol-2—yl)benzoic acid; and
`
`2-(4-nitro-phenyl)-4,5-diphenyl-lH-imidazole;
`
`or a pharmaceutically acceptable salt thereof.
`
`86.
`
`87.
`
`88.
`
`89.
`
`The method of claim 74, wherein the compound of Formula I is administered to
`
`the subject immediately prior to a meal.
`
`The method of claim 74, wherein the compound of Formula I is administered to a
`
`subject by way of a solid dosage form, orally disintegrating dosage form, liquid,
`
`aerosol, buccal patch, surgical implant, depot injection, or intravenous dosage
`
`form.
`
`The method of claim 74, wherein the subject in need of such treatment suffers
`
`from compulsive overeating disorder, bulimia, binge eating disorder, obesity,
`
`over-eating, or eating without care for stopping.
`
`The method of claim 74, wherein the reduced palatabiltiy of food results in a
`
`reduced caloric intake by the subject.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`90.
`
`91.
`
`92.
`
`93.
`
`94.
`
`95.
`
`96.
`
`-69-
`
`The method of claim 81, wherein the subject in need of such treatment suffers
`
`from type-II diabetes, or other diabetes related disorders.
`
`The method of claim 90, wherein the subject in need of such treatment has a body
`
`mass index of at least 30.
`
`The method of claim 74, wherein administering a compound of Formula I to a
`
`subject in need thereof decreases the caloric intake of the subject by at least about
`
`10%.
`
`The method of claim 74, wherein the compound of Formula I is administered as a
`
`pharmaceutical or food composition.
`
`The method of claim 93, wherein the compound of Formula I is present in the
`
`pharmaceutical or food composition in a concentration of about 0.01% to about
`
`50%, by weight, of the pharmaceutical or food composition.
`
`The method of claim 93, wherein the compound of Formula I is present in the
`
`pharmaceutical or food composition in an amount of about 0.01 mg to about 100
`
`mg.
`
`A pharmaceutical composition comprising one or more phamiaceutically
`
`acceptable carriers and one or more compounds of Formula 1:
`
`1
`
`Ar
`
`R1
`/
`N
`
`I
`
`/>iAr3
`
`A?
`
`N
`
`1
`
`or a pharmaceutically acceptable salt thereof; wherein:
`
`R1 is hydrogen, unsubstituted alkyl, or unsubstituted arylalkyl;
`
`Ar1 and Ar2 are independently phenyl or heteroaryl, either of which is optionally
`
`substituted; and
`
`Ar3 is phenyl or a heteroaryl, either of which is Optionally substituted.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-70-
`
`97.
`
`The pharmaceutical composition of claim 96, wherein Ar1
`
`and Ar2 are
`
`independently selected from the group consisting of phenyl, pyridyl, pyrimidinyl,
`
`pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl, any of which is optionally
`
`substituted.
`
`98.
`
`The pharmaceutical composition of claim 96, wherein Ar1
`
`and Ar2 are
`
`independently selected from the group consisting of unsubstituted phenyl,
`
`methylphenyl, methoxyphenyl,
`
`halophenyl,
`
`cyanophenyl,
`
`carboxyphenyl,
`
`aminophenyl, and hydroxyphenyl.
`
`99.
`
`The pharmaceutical composition of claim 96, wherein Ar1 and Ar2 are both
`
`unsubstituted phenyl.
`
`100.
`
`The pharmaceutical composition of claim 96, wherein Ar1 and Ar2 are both
`
`unubstituted: C—attached pyridyl, C—attached pyridazinyl, C-attached pyrimidinyl,
`
`C-attached pyrazinyl, C-attached triazinyl, or an N—oxide thereof.
`
`101.
`
`The pharmaceutical composition of claim 96, wherein Ar3 is selected from the
`
`group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl,
`
`pyrazinyl, and triazinyl, any of which is optionally substituted.
`
`102.
`
`The pharmaceutical composition of claim 96, wherein Ar3 is phenyl, pyrid-Z-yl,
`
`pyrid-3-yl,
`
`pyrid-4-yl,
`
`pyridazin-3-yl,
`
`pyridazin-4-y1,
`
`pyrimidin-Z-y],
`
`pyrimidin—4-yl, pyrimidin-S—yl, pyrazin-Z-yl, 1,2,3-triazin-4-yl, 1,2,3-triazin-5—yl,
`
`or 1,3,5-triazin-2-yl, any of which is optionally substituted.
`
`103.
`
`The pharmaceutical composition of claim 96, wherein AI3 is an unubstituted:
`
`C-attached pyridyl, C—attached pyridazinyl, C—attached pyrimidinyl, C-attached
`
`pyrazinyl, C-attached triazinyl, or an N—oxide thereof.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`-71-
`
`104.
`
`The pharmaceutical composition of claim 96, wherein Ar3 is selected from the
`
`group consisting of phenyl, C-attached pyridyl, C-attached pyrimidyl, and
`
`C-attached pyridazinyl, any of which is optionally substituted with one or more
`nitro, halo, cyano, carboxyl, amino, hydroxyl, alkyl, and cyanoalkyl substituents
`
`in any one of the ortho—, meta-, and para—positions.
`
`105.
`
`The pharmaceutical composition of claim 96, wherein:
`
`R1 is hydrogen, unsubstituted C1-4 alkyl, or unsubstituted aryl(C14)alkyl;
`
`Ar1 and Ar2 are both unsubstituted phenyl;
`
`Ar3 is phenyl, substituted by one to three substituents independently selected from
`
`the group consisting of carboxy, alkoxycarbonyl, hydroxy, hydroxyalkyl, amino,
`
`alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, and nitro.
`
`106.
`
`The pharmaceutical composition of claim 105, wherein Ar3 is phenyl, substituted
`
`in the para-position by one carboxy, alkoxycarbonyl, hydroxyalkyl, hydroxy,
`
`amino, alkoxycarbonylamino, cyano, alkylsulfonylaminoalkyl, or nitro.
`
`107.
`
`The pharmaceutical composition of claim 96, wherein the compound of Fomiula I
`
`is one of:
`
`methyl4-(4,5-diphenyl-1H-imidazol-2-yl)benzoate;
`
`[4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl]methanol;
`
`4-(4,5-dipheny1—1H-imidazol—2—yl)aniline;
`
`4—(4,5—dipheny1—IH—imidazol—Z-yl)phenol;
`
`methyl4-(4,5-diphenyl-1H—imidazol-2-y1)phenylcarbamate;
`
`N—[4-(4,5-diphenyl—1H-imidazol-2-yl)phenyl]acetamide;
`
`4-(4,5-diphenyl-IH-imidazol—Z-yl)benzonitrile; -
`
`N—[4-(4,5-diphenyl-1H—imidazol-Z-y1)benzyl]methanesulfonamide;
`
`4-(4,5—diphenyl-1H~imidazol-2—yl)benzoic acid; and
`
`2—(4-nitro-phenyl)-4,5-diphenyl-lH-imidazole;
`
`or a pharmaceutically acceptable salt thereof.
`
`Atty. Dkt. No. 2305.0330001/TJS/A—L
`
`
`
`108.
`
`109.
`
`110.
`
`111.
`
`112.
`
`113.
`
`114.
`
`115.
`
`-72-
`
`The pharmaceutical composition of claim 96, wherein the pharmaceutical
`
`composition is a solid dosage form.
`
`The pharmaceutical composition of claim 96, wherein the pharmaceutical
`
`composition is an orally disintegrating dosage form.
`
`The pharmaceutical composition of claim 96, wherein the pharmaceutical
`
`composition is a liquid dosage form.
`
`The pharmaceutical composition of claim 96, wherein the pharmaceutical
`
`composition is a suspension.
`
`The pharmaceutical composition of claim 96, wherein the pharmaceutical
`
`composition is an aerosol composition.
`
`The pharmaceutical composition of claim 96, wherein the compound of Formula I
`
`is present
`
`in an amount of about 0.01% to about 50%, by weight, of the
`
`pharmaceutical composition.
`
`The pharmaceutical composition of claim 96, further comprising an biologically
`
`active agent that is other than a compound of Formula I.
`
`The pharmaceutical composition of claim 114, wherein the biologically active
`
`agent is selected from the group consisting of analgesics, anesthetics, anorexiants,
`
`appetite depressants,
`
`antacidics,
`
`antiasthmatics,
`
`antidiuretics,
`
`antipyretics,
`
`antihistamines,
`
`anticholinergics,
`
`antidiarrheals,
`
`antitussives,
`
`antinauseants,
`
`antiarrhythmics,
`
`antimicrobials,
`
`antibacterials,
`
`antifungals,
`
`antivirals,
`
`anti-
`
`inflammatory agents, agents active against flatulence, antimigraine agents, beta-
`
`receptor blockers, bronchodilators, psychopharrnacological agents, spasmolytics,
`
`sedatives, antihyperkinetics, tranquilizers, decongestants, demulcents, agents for
`
`alcohol withdrawal, antitussives, fluorine supplements, laxatives, local antibiotics,
`
`corticosteroid supplements, agents against goiter formation, antiepileptics, agents
`
`Atty. Dkt. No. 2305.0330001/TJS/A—L
`
`
`
`-73-
`
`against dehydration, antiseptics, NSAIDs, Hz—receptor antagonists, nutritional
`
`supplements, gastrointestinal active agents, alkaloids, supplements for
`
`trace
`
`elements,
`
`ion-exchange resins, cholesterol-depressant agents,
`
`lipid-lowering
`
`agents, expectorants, and combinations thereof.
`
`116.
`
`A method of preparing an improved pharmaceutical composition, wherein the
`
`improvement comprises adding to a pharmaceutical composition one or more
`
`compounds of Formula I:
`
`R1
`/
`N
`
`I
`
`/>7Ar3
`N
`
`1
`
`1
`
`Ar
`
`Ar2
`
`or a pharmaceutically acceptable salt thereof; wherein:
`
`RI is hydrogen, unsubstituted alkyl, or unsubstituted arylalkyl;
`Ar1 and Ar2 are independently phenyl or heteroaryl, either of which is optionally
`
`substituted; and
`
`Ar3 is phenyl or a heteroaryl, either of which is optionally substituted.
`
`117.
`
`The method of claim 116, wherein Ar1 and A12 are independently selected from
`
`the group consisting of phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl,
`
`pyrazinyl, and triazinyl, any of which is optionally substituted.
`
`118.
`
`The method of claim 116, wherein Arl and Ar2 are independently selected from
`
`the group consisting of unsubstituted phenyl, methylphenyl, methoxyphenyl,
`
`halophenyl, cyanophenyl, carboxyphenyl, aminophenyl, and hydroxyphenyl.
`
`119.
`
`120.
`
`The method of claim 116, wherein Ar1 and Ar2 are both unsubstituted phenyl.
`
`The method of claim 116, wherein Ar1 and Ar2 are both unubstituted C-attached
`
`pyridyl, C-attached pyridazinyl, C-attached pyrimidinyl, C—attached pyrazinyl, C-
`
`attached triazinyl, or an N—oxide thereof.
`
`Atty. Dkt. No. 2305.0330001/TJS/A-L
`
`
`
`121.
`
`The method of claim 116, wherein AI3 is selected from the group consisting of
`
`-74-
`
`phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrimidinyl, pyrazinyl, and triazinyl,
`
`any of which is optionally substituted by one to three groups independently
`
`selected from the group consisting of amino, hydroxy, nitro, nitroso, halogen,
`
`cyano,
`
`isocyano,
`
`azido,
`
`thiol,
`
`carboxy,
`
`(C1-1o)alkyl,
`
`amino(C1-.o)alkyl,
`
`hydroxy(C I -10) alkyl,
`
`halo(C1_1o)alkyl,
`
`cyano(C1-1o)alkyl,
`
`thio(C1-10)alkyl,
`
`carboxy(C1_10)a1kyl,
`
`ary1(C1_10)alkyl,
`
`(C1-10)alkoxy(C1-1o)alkyl,
`
`(C2-10)alkenyl,
`
`amino(C3-10)alkenyl,
`
`hydroxy(C3-1o)alkenyl,
`
`halo(C2-io)alkeny1,
`
`cyano(C2.
`
`10)alkeny1,
`
`thio(C3_1o)alkenyl,
`
`carboxy(C3_1o)alkenyl,
`
`aryl(C2.1o)alkenyl,
`
`(C2-
`
`10)a1kynyl,
`
`(Cl—10)heteroalkyl,
`
`(C2-1o)heteroa1kenyl,
`
`(C2-1o)heteroalkynyl,
`
`(C1-
`
`10)alkoxy,
`
`(C3_10)alkenyloxy,
`
`(C1-10)alkylenedioxy,
`
`amino(C2-10)a]koxy,
`
`,hydroxy(C2_10)alkoxy, halo(C1_10)alkoxy, cyano(C1_1o)alkoxy,
`
`thio(C1-m)alkoxy,
`
`carboxy(C2-1 0)a1koxy,
`
`aryl(C1-1o)alk0xy,
`
`(C 1 -1 o)alkoxy(C2-1 o)alkoxy,
`
`mono(C1 -1o)a1kylamino,
`
`di(C1-10)alky1amino,
`
`(C1-10)a1kylcarbonylamino,
`
`(C24o)alkenylcarbonylamino,
`
`(C6-14)arylcarbonylamino,
`
`(C1 -10)alkoxycarbonylamino,
`
`(C6-10)aryloxycarbonylamino,
`
`(C1_1o)alkylcarbonyl,
`
`(C2-1o)alkenylcarbonyl,
`
`(C6-lo)arylcarbonyl,
`
`(C1-lo)alkoxycarbonyl,
`
`(C6_14)aryloxycarbonyl,
`
`(C 1-1o)alkylsulfonylamino,
`
`(C2
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