In humans, bitter taste is mediated by 25 TAS2Rs. Many compounds, including certain active pharmaceutical ingredients, excipients, and nutraceuticals, impart their bitter taste (or in part) through TAS2R8 activation. However, effective TAS2R8 blockers that can either suppress or reduce the bitterness of these compounds have not been described. We are hereby reporting a series of novel 3-(pyrazol-4-yl) imidazolidine-2,4-diones as potent and selective TAS2R8 antagonists. In human sensory tests, S6821 and S7958, two of the most potent analogues from the series, demonstrated efficacy in blocking TAS2R8-mediated bitterness and were selected for development. Following data evaluation by expert panels of a number of national and multinational regulatory bodies, including the US, the EU, and Japan, S6821 and S7958 were approved as safe under conditions of intended use as bitter taste blockers.

A compound having structural Formula (I): ** ** Formula or a salt or solvate thereof, wherein R1 and R2 are independently hydrogen or C1 to C6 alkyl; L is C1 to C12 alkylene or C1 to C12 alkyl; M is -NR4-C (O) - or -C (O) -NR4-; R4 is hydrogen or C1 to C6 alkyl; or alternatively, when M is -NR4-C (O) -, R4 and one or more atoms of L, together with the nitrogen to which they are attached form a heterocyclic ring of 5 to 8-membered is optionally substituted; and R3 is C1 to C12 alkyl, C1 to C12 alkyl, 5- to 8-membered or 5- to 8-membered substituted; wherein, when it indicates that a group is substituted, the one or more substituents selected from the group consisting of halo, amino, N-alkylamino, N, N-dialkylamino, hydroxyl, alkoxy, alkyl, aryl, heteroaryl, heterocyclyl, carbocyclyl,> = O,> = S,> = NR> = NORA, -CN, -C (O) Rb, -C (O) ORa, -C (O) NR a R, -OC (O) OH, - OC (O) ORa, -NRaC (O) Rb, -NRaC (O) ORa and -NRaC (O) NR a R, wherein each R is independently hydrogen or alkyl including linear, branched and cyclic; or, alternatively, two R, taken together with the nitrogen to which they are attached form a heterocyclic ring; and each Rb is alkyl including linear, branched and cyclic alkyl; with the proviso that the compound is not 4-amino-5- (2,2-dimethyl-3-oxo-3- (propylamino) propoxy) -2-methyl-quinolin-3-carboxylic acid.

A compound of the formula: ** ** Formula or a salt or N-oxide thereof, wherein Alk is an alkyl group; M1 is N or CR49, wherein R49 is H or substituted alkyl or unsubstituted; M2 is N or CR50, wherein R50 is H or substituted alkyl or unsubstituted; R36 and R37, together with the atoms to which they are attached form a five- or six-membered optionally substituted; and R38 is H, substituted or unsubstituted cycloalkylalkyl substituted or unsubstituted, substituted heterocycloalkyl or unsubstituted aryl, substituted or unsubstituted, substituted arylamidoalkyl or unsubstituted, substituted heteroarilamidoalquilo or unsubstituted, substituted aryl or unsubstituted aryl substituted or unsubstituted, heteroaryl substituted or unsubstituted heteroarylalkyl substituted or unsubstituted, or haloalkyl, R47 is H, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted, substituted arylalkyl or unsubstituted or halo; and R48 is H, substituted or unsubstituted alkoxy, substituted or unsubstituted aryl, substituted or unsubstituted, substituted or unsubstituted arylalkyl, or halo.

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