TRIPHENYLPHOSPHINE OXIDE DERIVATIVES AND USES THEREOF
The present invention is directed to the use of a compound having the formula wherein R 1 , R 2 , R 3 , m, n and p are defined herein. The compounds of the present invention are useful as inhibitors of certain taste perceptions and functions. The invention is also directed to compositions comprising a compound according to the above formula.
1 . A method of inhibiting a taste modulating protein, comprising contacting said protein with a compound of Formula I:
or a physiologically acceptable salt thereof, wherein
R 1 , R 2 and R 3 are independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, C 1-6 alkoxy, amino, C 1-6 alkylamino, C 1-6 dialkylamino, and halo; and
m, n, and p are independently an integer from 0 to 5.
2 . The method according to claim 1 , wherein R 1 , R 2 , and R 3 are hydrogen.
3 . The method according to claim 1 , wherein R 1 and R 2 are hydrogen.
4 . The method according to claim 1 , wherein at least one of R 1 , R 2 , and R 3 is hydroxy.
5 . The method according to claim 1 , wherein R 3 is an amino group.
6 . The method according to claim 1 , wherein R 3 is methoxy.
7 . The method according to claim 1 , wherein R 3 is diethylamino.
8 . The method according to claim 1 , wherein the compound of Formula I is
9 . The method according to claim 1 , wherein the compound of Formula I is
10 . The method according to claim 1 , wherein the compound of Formula I is
11 . The method according to claim 1 , wherein the compound of Formula I is
12 . The method according to claim 1 , wherein the compound of Formula I is
13 . The method according to claim 1 , wherein the compound of Formula I is
14 . The method according to claim 1 , wherein the protein is a nonhuman TRPM5 protein.
15 . The method according to claim 1 , wherein the protein is a cow, horse, sheep, pig, cat, dog, rabbit, or monkey TRPM5 protein.
16 . The method according to claim 1 , wherein the protein is a human TRPM5 protein.
17 . The method according to claim 1 , wherein the compound according to Formula I is administered as a pharmaceutical composition.
18 . The method according to claim 1 , wherein the compound according to Formula I is administered as a veterinary composition.
19 . The method according to claim 1 , wherein the compound according to Formula I is administered as a food composition.
20 . The method according to claim 1 , wherein the compound according to Formula I is administered as a dental hygienic composition.
21 . The method according to claim 1 , wherein the compound according to Formula I is administered in a concentration from about 1% to about 10% on a weight percentage basis.
22 . The method according to claim 1 , wherein the compound according to Formula I is administered in an amount of about 0.01 mg to about 10 mg.
23 . The method according to claim 1 , wherein said receptor is in vitro.
24 . A method of inhibiting a taste, comprising administering to a subject in need of said taste inhibiting one or more compounds of Formula I:
or a physiologically acceptable salt thereof, wherein
R 1 , R 2 and R 3 are independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, C 1-6 alkoxy, amino, C 1-6 alkylamino, C 1-6 dialkylamino, and halo; and
m, n, and p are independently an integer from 0 to 5;
wherein said compound is administered in an amount sufficient to inhibit said taste.
25 . A method of inhibiting the depolarization of a taste receptor cell, comprising contacting said taste receptor cell with one or more compounds of Formula I:
or a physiologically acceptable salt thereof, wherein
R 1 , R 2 and R 3 are independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, C 1-6 alkoxy, amino, C 1-6 alkylamino, C 1-6 dialkylamino, and halo; and
m, n, and p are independently an integer from 0 to 5.
26 . A pharmaceutical composition comprising one or more pharmaceutically acceptable carriers and one or more compounds according to Formula I:
or physiologically acceptable salt thereof wherein
R 1 , R 2 and R 3 are independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, C 1-6 alkoxy, amino, C 1-6 alkylamino, C 1-6 dialkylamino, and halo; and
m, n, and p are independently an integer from 0 to 5.
27 . A method of preparing an improved pharmaceutical composition, wherein the improvement comprises adding to a pharmaceutical composition one or more compounds according to Formula I:
or physiologically acceptable salt thereof wherein R 1 , R 2 and R 3 are independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, hydroxy, C 1-6 alkoxy, amino, C 1-6 alkylamino, C 1-6 dialkylamino, and halo; and
m, n, and p are independently an integer from 0 to 5.