N-formamidopyrazoline derivative as P2X3 receptor antagonist and use thereof

1 . An N-formamidopyrazoline compound of General Formula (I), or an enantiomer, a diastereomer, a racemate thereof, or a pharmaceutically acceptable salt thereof:

wherein

Ar is selected from 1,3-benzodioxole; or Ar is selected from the following substituted phenyls, substitute five-membered or six-membered heteroaromatic ring groups:

R 5 and R 6 are independently selected from the group consisting of H, halogen, nitryl, cyano group, methyl, trifluoromethyl, trifluoromethoxy, and C1 to C3 straight or branched chain alkoxy; and

R 7 is selected from methyl, ethyl, isopropyl, and cyclopropyl;

R 1 is selected from substituted or unsubstituted phenyl or substituted or unsubstituted pyridyl, wherein R 1 is substituted with a group selected from halogen, C1 to C3 straight or branched chain alkyl, C1 to C3 straight or branched chain alkoxy, trifluoromethyl and trifluoromethoxy; and R 2 is selected from a methyl, an ethyl, an isopropyl and a cyclopropyl; and

wherein the R 3 and the R 4 are each independently selected from H, methyl, ethyl, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl, formyl, acetyl, and N,N-dialkylaminoacetyl; or the R 3 and the R 4 together with the N to which they both are connected form substituted or unsubstituted morpholinone, substituted or unsubstituted morpholinyl, substituted or unsubstituted piperidinyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted piperazinone, substituted or unsubstituted pyrrolidone, substituted or unsubstituted oxazolidinone, substituted or unsubstituted imidazolidinone, substituted or unsubstituted imidazolyl, substituted or unsubstituted pyrazolyl, 1,2,3-triazolyl, and 1,2,4-triazolyl; and

wherein substituted groups on morpholinone, morpholinyl, piperidinyl, piperazinyl, piperazinone, pyrrolidone, oxazolidinone, imidazolidinone, imidazolyl and pyrazolyl are selected from C1 to C3 straight or branched chain alkyl, formyl, acetyl, and C1 to C5 straight or branched chain alkoxy.

2 . The N-formamidopyrazoline compound according to claim 1 having General Formulas (Ia), (Ib), (Ic) and (Id):

3 . The N-formamidopyrazoline compound according to claim 2 , wherein the Ar is selected from phenyl, p-trifluoromethylphenyl, dimethoxyphenyl, dioxolane phenyl, p-cyanophenyl, chlorophenyl, methoxypyridyl, trifluoromethyl pyridyl, chloropyridyl, difluoropyridyl, trifluoromethyloxypyridyl, trifluoromethylpyrazinyl, methylpyrazinyl, chloropyrazinyl, methoxypyridazinyl, trifluoromethylpyridazinyl, chloropyridazinyl, trifluoromethylpyrimidinyl, methylpyrimidinyl, chloropyrimidinyl, and methyl-1,2,4-oxadiazolyl;

the R 1 is selected from p-methylphenyl, p-methoxyphenyl, p-fluorophenyl, p-chlorophenyl, and methylpyridyl; and

the R 2 is selected from methyl; and the R 3 and the R 4 are each independently selected from H, methyl, ethyl, methoxycarbonyl, ethoxycarbonyl, acetyl, and N,N-dialkylaminoacetyl; or the R 3 and the R 4 together with the N to which they both are connected form morpholinone, piperazinone, methylpiperazinone, pyrrolidone, oxazolidinone, imidazolidinone, acetyl imidazolidinone, morpholinyl, piperazinyl, N-acetylpiperazinyl, and pyrazolyl.

4 . The N-formamidopyrazoline compound according to claim 1 , wherein the compound in General Formula (I) is one of the following compounds:

(S)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (1)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (1a) (S)-4-(4-methyl-2-oxopiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(4-chlorophenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (2)

(R)-4-(4-methyl-2-oxopiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(4-chlorophenyl))ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (2a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (3)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (3a)

(S)-4-(N-methyl-N-ethoxycarbonylamino)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (4)

(R)-4-(N-methyl-N-ethoxycarbonylamino)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (4c)

(S)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (5)

(R)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (5a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(3,4-dimethoxyphenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (6)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(3,4-dimethoxyphenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (6a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(3,4-(methylenedioxy)phenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (7)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(3,4-(methylenedioxy)phenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (7a)

(S)-4-(3-acetyl-2-oxoimidazolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(4-cyanophenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (8)

(R)-4-(3-acetyl-2-oxoimidazolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(4-cyanophenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (8a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(5-methoxypyridin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (9)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(5-methoxypyridin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (9a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(5-(trifluoromethyl) pyridin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (10)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(5-(trifluoromethyl) pyridin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (10a)

(S)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(6-chloropyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (11)

(R)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(6-chloropyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (11a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(5,6-difluoropyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (12)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(5,6-difluoropyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (12a) (S)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethoxy)pyridin)-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (13)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethoxy)pyridin)-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (13a)

(S)-4-(morpholin-4-yl)-3-(4-fluorophenyl)-N—((R)-1-(6-methoxypyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (14)

(R)-4-(morpholin-4-yl)-3-(4-fluorophenyl)-N—((R)-1-(6-methoxypyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (14a)

(S)-4-(2-(dimethylamino)-N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (15)

(R)-4-(2-(dimethylamino)-N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (15a)

(S)-4-(N-methyl-N-methoxycarbonylamino)-3-(4-methoxyphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (16)

(R)-4-(N-methyl-N-methoxycarbonylamino)-3-(4-methoxyphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (16a)

(S)-4-(4-methyl-2-oxopiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (17)

(R)-4-(4-methyl-2-oxopiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (17a)

(S)-4-(3-acetyl-2-oxoimidazolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (18)

(R)-4-(3-acetyl-2-oxoimidazolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (18a)

(S)-4-(4-acetylpiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (19)

(R)-4-(4-acetylpiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (19a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (20)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(4-(trifluoromethyl)phenyl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (20a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (21)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (21a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (22)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (22a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(5-methylpyridin-2-yl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (23)

(R)-4-(2-oxooxazolidin-3-yl)-3-(5-methylpyridin-2-yl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (23a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-fluorophenyl)-N—((R)-1-(2-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (24)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-fluorophenyl)-N—((R)-1-(2-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (24a)

(S)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (25)

(R)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (25a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(5-(trifluoromethyl) pyrazin)-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (26)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(5-(trifluoromethyl) pyrazin)-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (26a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(5-methylpyrazin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (27)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(5-methylpyrazin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (27a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-fluorophenyl)-N—((R)-1-(5-methylpyrazin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (28)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-fluorophenyl)-N—((R)-1-(5-methylpyrazin-2-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (28a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-chlorophenyl)-N—((R)-1-(6-(methoxy)pyridazin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (29)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-chlorophenyl)-N—((R)-1-(6-(methoxy)pyridazin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (29a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl)pyridazin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (30)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(6-(trifluoromethyl)pyridazin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (30a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(6-chloropyridazin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (31)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(6-chloropyridazin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (31a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (32)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (32a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-fluorophenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (33)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-fluorophenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (33a)

(S)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (34)

(R)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (34a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-chlorophenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (35)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-chlorophenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (35a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-methoxyphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (36)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-methoxyphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (36a)

(S)-4-(4-acetylpiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (37)

(R)-4-(4-acetylpiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (37a)

(S)-4-(4-methylpiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (38)

(R)-4-(4-methylpiperazin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (38a)

(S)-4-(morpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (39)

(R)-4-(morpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (39a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (40)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-methylphenyl)-N—((R)-1-(2-(trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (40a)

(S)-4-(3-methyl-2-oxoimidazolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (41)

(R)-4-(3-methyl-2-oxoimidazolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (41a)

(S)-4-(pyrazol-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (42)

(R)-4-(pyrazol-1-yl)-3-(4-methylphenyl)-N—((R)-1-(2-trifluoromethyl)pyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (42a)

(S)-4-(2-oxooxazolidin-3-yl)-3-(4-chlorophenyl)-N—((R)-1-(2-methylpyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (43)

(R)-4-(2-oxooxazolidin-3-yl)-3-(4-chlorophenyl)-N—((R)-1-(2-methylpyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (43a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-fluorophenyl)-N—((R)-1-(2-chloropyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (44)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-fluorophenyl)-N—((R)-1-(2-chloropyrimidin-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (44a)

(S)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (45)

(R)-4-(2-oxopyrrolidin-1-yl)-3-(4-methylphenyl)-N—((R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (45a)

(S)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (46)

(R)-4-(3-oxomorpholin-4-yl)-3-(4-methylphenyl)-N—((R)-1-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (46a) (S)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((S)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (47)

(R)-4-(N-methylacetamido)-3-(4-methylphenyl)-N—((S)-1-(6-(trifluoromethyl) pyridin-3-yl)ethyl)-4,5-dihydro-1H-pyrazol-1-carboxamide (47a).

5 . The N-formamidopyrazoline compound according to claim 1 , wherein the pharmaceutically acceptable salt is selected from pharmaceutically acceptable inorganic acid salts and organic acid salts; the inorganic acid salts comprise salts formed with haloid acid, nitric acid, carbonic acid, sulfuric acid or phosphoric acid; and the organic acid salts comprise salts formed with malic acid, citric acid, fumaric acid, oxalic acid, lactic acid, camphorsulfonic acid, p-toluenesulfonic acid, methanesulfonic acid and benzoic acid.

6 . A method of treating diseases comprising administering a compound of claim 1 , wherein the diseases comprise cough.

7 . A pharmaceutical composition comprising the N-formamidopyrazoline compound of claim 1 and one or more pharmaceutically acceptable carriers or excipients.

8 . The pharmaceutical composition according to claim 7 , wherein the carriers or excipients comprise one or more of filler, diluent, wetting agent, lubricant, binder, disintegrant, absorption enhancer, surfactant, adsorption carrier, antioxidant, metal chelating agent, pH conditioning agent, flavouring agent, and sweetening agent.

9 . The pharmaceutical composition of claim 7 wherein the composition is in the form of tablets, capsules, inhalants, emulsions, suspensions, gels, powders, granules, oral liquids and injections.

10 . A method of treating cough mediated by P2X3 comprising the step of administering the N-formamidopyrazoline compound of claim 1 to a subject.