DK2968297T3 - Multisubstituerede aromatiske forbindelser som serinproteasehæmmere - Google Patents

Multisubstituerede aromatiske forbindelser som serinproteasehæmmere Download PDF

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DK2968297T3
DK2968297T3 DK14764515.4T DK14764515T DK2968297T3 DK 2968297 T3 DK2968297 T3 DK 2968297T3 DK 14764515 T DK14764515 T DK 14764515T DK 2968297 T3 DK2968297 T3 DK 2968297T3
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methyl
amino
pyrazol
unsubstituted
chlorothiophen
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Kevin Michael Short
Son Minh Pham
David Charles Williams
David Ben Kita
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Verseon Inc
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Claims (23)

1. Forbindelse til anvendelse i behandling af en sygdom eller forstyrrelse hos et individ, hvilken forbindelse har formlen (V):
eller farmaceutisk acceptabelt salt, ester, solvat eller prodrug deraf; hvor L1 er-NR7-; L2 er -C(O)-; L5 er en binding, substitueret eller usubstitueret alkylen, substitueret eller usubstitueret heteroalkylen, -S-, -SO-, -SO2-, -O-, -NHSO2- eller-NR7-; R1 er hydrogen, halogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret cycloalkenyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret heterocycloalkenyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, eller substitueret eller usubstitueret heteroaryl; R2 er substitueret eller usubstitueret alkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret cycloalkenyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret heterocycloalkenyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, eller substitueret eller usubstitueret heteroaryl; R5 er hydrogen, halogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret cycloalkenyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret heterocycloalkenyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, eller substitueret eller usubstitueret heteroaryl; og R7 er hydrogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret cycloalkenyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret heterocycloalkenyl, substitueret eller usubstitueret aryl, eller substitueret eller usubstitueret heteroaryl; og
hvor en hvilken som helst substitueret gruppe kan være substitueret med én eller flere substituentgrupper valgt fra følgende dele: (A) -OH, -NH2, -SH, -CN, -CF3, -NO2, oxo, halogen, -COOH, usubstiitueret Ci-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalky, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (B) Ci-C24-alkyl, 2- til 20 leddet heteroalkyl, C3-Cs-cycloalky„ 4- til 8-leddet heterocycloalkyl, aryl, og heteroaryl, substitueret med mindst én substituent valgt fra: (i) oxo, -OH, -NH2, -SH, -CN, -CF3, -NO2, halogen, -COOH, usubstiitueret Ci-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalky, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (ii) C, -C24-alkyl, heteroalkyl, C3-C8-cycloalky, 4- til 8-leddet heterocycloalkyl, aryl, og heteroaryl, substitueret med mindst én substituent valgt fra: (a) oxo, -OH, -NH2, -SH, -CN, -CF3, -N02, halogen, -COOH, usubstiitueret C1-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalkyl, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (b) CrC24-alkyl, 2- til 20- leddet heteroalkyl, cycloalkyl, 4- til 8-leddet heterocycloalkyl, aryl, eller heteroaryl, substitueret med mindst én substituent valgt fra: oxo, -OH, -NH2, -SH, -CN, -CF3, -NO2, halogen, -COOH, usubstitueret Ci-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalky, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, og usubstitueret heteroaryl.
2. Forbindelse til anvendelse i behandling af en sygdom eller forstyrrelse hos et individ, hvilken forbindelse har formlen (VI):
et farmaceutisk acceptabelt salt, ester, solvat eller prodrug deraf; hvor L1 er-NR7-; L5 er en binding, substitueret eller usubstitueret alkylen, substitueret eller usubstitueret heteroalkylen, -S-, -SO-, -SO2-, -O-, -NHSO2-, eller-NR7-; R1 er hydrogen, halogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret cycloalkenyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret
heterocycloalkenyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, eller substitueret eller usubstitueret heteroaryl; R5 er hydrogen, halogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret cycloalkenyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret heterocycloalkenyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, eller substitueret eller usubstitueret heteroaryl; og R7 er hydrogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret cycloalkenyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret heterocycloalkenyl, substitueret eller usubstitueret aryl, eller substitueret eller usubstitueret heteroaryl; og hvor en hvilken som helst substitueret gruppe kan være substitueret med én eller flere substituentgrupper valgt fra følgende dele: (A) -OH, -NH2, -SH, -CN, -CF3, -NO2, oxo, halogen, -COOH, usubstitueret Ci-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalkyl, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (B) C1-C24-alkyl, 2- til 20 leddet heteroalkyl, C3-C8-cycloalkyl, 4- til 8-leddet heterocycloalkyl, aryl, og heteroaryl, substitueret med mindst én substituent valgt fra: (i) oxo, -OH, -NH2, -SH, -CN, -CF3, -NO2, halogen, -COOH, usubstitueret C1-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalkyl, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (ii) C, -C24-alkyl, heteroalkyl, C3-C8-cycloalkyl, 4- til 8-leddet heterocycloalkyl, aryl, og heteroaryl, substitueret med mindst én substituent valgt fra: (a) oxo, -OH, -NH2, -SH, -CN, -CF3, -N02, halogen, -COOH, usubstitueret Ci-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalkyl, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (b) Ci-C24-alkyl, 2- til 20-leddet heteroalkyl, cycloalkyl, 4- til 8-leddet heterocycloalkyl, aryl, eller heteroaryl, substitueret med mindst én substituent valgt fra: oxo, -OH, -NH2, -SH, -CN, -CF3, -NO2, halogen, -COOH, usubstitueret Ci-C24-alkyl, usubstitueret 2- til 20 leddet heteroalkyl, usubstitueret C3-C8-cycloalkyl, usubstitueret 4- til 8-leddet heterocycloalkyl, usubstitueret aryl, og usubstitueret heteroaryl.
3. Forbindelse til anvendelse ifølge krav 1, hvor R2 er substitueret eller usubstitueret aryl eller substitueret eller usubstitueret heteroaryl, eventuelt hvor R2 er heteroaryl valgt fra gruppen bestående af substitueret eller usubstitueret pyridyl, substitueret eller usubstitueret pyridazinyl, substitueret eller usubstitueret pyrimidinyl, substitueret eller usubstitueret thienyl og substitueret eller usubstitueret furyl.
4. Forbindelse til anvendelse ifølge krav 1, hvor R2 er substitueret eller usubstitueret alkyl, substitueret eller usubstitueret cycloalkyl, eller substitueret eller usubstitueret heterocycloalkyl; eventuelt hvor R2 er heterocycloalkyl valgt fra gruppen bestående af substitueret eller usubstitueret oxanyl, substitueret eller usubstitueret oxetanyl og substitueret eller usubstitueret morpholinyl.
5. Forbindelse til anvendelse ifølge krav 1, hvor R2 er substitueret eller usubstitueret kondenseret ringaryl; eventuelt hvor R2 er kondenseret ringaryl valgt fra gruppen bestående af substitueret eller usubstitueret benzodioxinyl og substitueret eller usubstitueret naphthyl.
6. Forbindelse til anvendelse ifølge et hvilket som helst foregående krav, hvor R1 er hydrogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, substitueret eller usubstitueret heteroaryl eller substitueret eller usubstitueret heterocycloalkyl.
7. Forbindelse til anvendelse ifølge krav 6, hvor R1 er substitueret eller usubstitueret heteroaryl; eventuelt hvor R1 er heteroaryl valgt fra gruppen bestående af substitueret eller usubstitueret pyridyl, substitueret eller usubstitueret pyridazinyl, substitueret eller usubstitueret pyrimidinyl, substitueret eller usubstitueret thienyl, og substitueret eller usubstitueret furyl; endvidere eventuelt hvor R1 er chlor-substitueret thienyl; eller hvor R1 er substitueret eller usubstitueret heterocycloalkyl; eventuelt hvor R1 er heterocycloalkyl valgt fra gruppen bestående af substitueret eller usubstitueret morpholinyl, substitueret eller usubstitueret oxanyl, og substitueret eller usubstitueret oxetanyl; eller hvor R1 er substitueret eller usubstitueret kondenseret ringaryl; eventuelt hvor R1 er kondenseret ringaryl valgt fra gruppen bestående af substitueret eller usubstitueret benzodioxinyl og substitueret eller usubstitueret naphthyl.
8. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 1 til 7, hvor L5 er en binding eller substitueret eller usubstitueret alkylen, og R5 er substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl eller substitueret eller usubstitueret heteroaryl.
9. Forbindelse til anvendelse ifølge krav 8, hvor R5 er substitueret eller usubstitueret heteroaryl; eventuelt hvor R5 er heteroaryl valgt fra gruppen bestående af substitueret eller usubstitueret pyridyl, substitueret eller usubstitueret pyridazinyl, substitueret eller usubstitueret pyrimidinyl, substitueret eller usubstitueret thienyl og substitueret eller usubstitueret furyl.
10. Forbindelse til anvendelse ifølge krav 8, hvor R5 er substitueret eller usubstitueret kondenseret ringaryl; eventuelt hvor R5 er kondenseret ringaryl valgt fra gruppen bestående af substitueret eller usubstitueret benzodioxinyl og substitueret eller usubstitueret naphthyl.
11. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 1 til 7, hvor L5 er substitueret eller usubstitueret alkylen, og R5 er substitueret eller usubstitueret heterocycloalkyl; eventuelt hvor R5 er heterocycloalkyl valgt fra gruppen bestående af substitueret eller usubstitueret morpholinyl, substitueret eller usubstitueret oxanyl og substitueret eller usubstitueret oxetanyl.
12. Forbindelse til anvendelse ifølge krav 1, hvor forbindelsen har en struktur med formlen A eller formlen B:
hvor Rx og Rz er uafhængigt valgt fra hydrogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, og substitueret eller usubstitueret heteroaryl; og Ry er uafhængigt valgt fra substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl og substitueret eller usubstitueret heteroaryl; hvor en hvilken som helst Rx, RY eller Rz substitueret gruppe er substitueret med mindst én substituent valgt fra: (i) oxo, -OH, -NH2, -SH, -CN, -CF3, -N02, halogen, -COOH, usubstitueret alkyl, usubstitueret heteroalkyl, usubstitueret cycloalkyl, usubstitueret heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og
(ii) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl og heteroaryl, substitueret med mindst én substituent valgt fra: (a) oxo, -OH, -NH2, -SH, -CN, -CF3, -N02, halogen, -COOH, usubstitueret alkyl, usubstitueret heteroalkyl, usubstitueret cycloalkyl, usubstitueret heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (b) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, eller heteroaryl, substitueret med mindst én substituent valgt fra: oxo, -OH, -NH2, -SH, -CN, -CF3, -N02„ halogen, -COOH, usubstitueret alkyl, usubstitueret heteroalkyl, usubstitueret cycloalkyl, usubstitueret heterocycloalkyl, usubstitueret aryl og usubstitueret heteroaryl.
13. Forbindelse til anvendelse ifølge krav 2, hvor forbindelsen har en struktur med formlen C:
hvor Rx er uafhængigt valgt fra hydrogen, substitueret eller usubstitueret alkyl, substitueret eller usubstitueret heteroalkyl, substitueret eller usubstitueret cycloalkyl, substitueret eller usubstitueret heterocycloalkyl, substitueret eller usubstitueret aryl, substitueret eller usubstitueret kondenseret ringaryl, og substitueret eller usubstitueret heteroaryl; hvor en hvilken som helst Rx substitueret gruppe er substitueret med miindst én substituent valgt fra: (i) oxo, -OH, -NH2, -SH, -CN, -CF3, -N02, halogen, -COOH, usubstitueret alkyl, usubstitueret heteroalkyl, usubstitueret cycloalkyl, usubstitueret heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (ii) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, og heteroaryl, substitueret med mindst én substituent valgt fra: (a) oxo, -OH, -NH2, -SH, -CN, -CF3, -N02, halogen, -COOH, usubstitueret alkyl, usubstitueret heteroalkyl, usubstitueret cycloalkyl, usubstitueret heterocycloalkyl, usubstitueret aryl, usubstitueret heteroaryl, og (b) alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, eller heteroaryl, substitueret med mindst én substituent valgt fra: oxo, -OH, -NH2, -SH, -CN, -CF3, -N02„ halogen, -COOH, usubstitueret alkyl, usubstitueret heteroalkyl, usubstitueret cycloalkyl, usubstitueret heterocycloalkyl, usubstitueret aryl og usubstitueret heteroaryl.
14. Forbindelse til anvendelse ifølge krav 1 eller krav 2, hvor forbindelsen er valgt fra:
3-(5-amino-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 -(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -methyl-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 1 -[(2-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-[(2-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-[(2-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1 -[(2-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3H-pyrazol-3-yl)- 1,2-dihydropyridin-2-on; 1-[(3-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino- 1- (2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1 -[(3- chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-[(3-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen- 2- yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1 -[(3- chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-[(4-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1 -[(4-chlorphenyl)methyl]- 3- (5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1H-pyrazol-3-yl)- 1,2-dihydropyridin-2-on; 1-[(4-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1 -[(4-chlorphenyl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-[(5-chlorthiophen-2-yl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-[(5-chlorthiophen-2-yl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-[(5-chlorthiophen-2-yl)methyl]-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)- 1,2-dihydropyridin-2-on; 1 -[(5-chlorthiophen-2-yl)methyl]-3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1- benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1 -benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1 -benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-2- yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-3- yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 1-benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[4-(morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1,2-d i hyd ropy ri d i n-2-on; 1 -benzyl-3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1,2-d i hyd ropyrid i n-2-on; 1-benzyl-3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol- 3-y I-1,2-dihydropyridin-2-on; 2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(2,2- dimethylpropanoyl)-1H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridin-1-yl]acetonitril; 2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridin-1 -yljacetonitril; 2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3- yl)carbonyl]-1 H-pyrazol-3-yl)-2-oxo-1,2-d ihyd ropyrid in-1 -yljacetonitril; 2-[3-(5-[(5- chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridin-1-yl]eddikesyre; 2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-2-oxo-1,2-d i hyd ropy rid i n-1 -y Ijaceton itri I; 3-(1 -benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1,2- dihydropyridin-2-on; 3-(1 -benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(1-benzoyl-5-[(5-chlorthiophen-2- yl)methyl]amino-1 H-pyrazol-3-yl)-1-(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(1-benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(1-benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(1-benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(1-benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(pyrid i n-3-y I methy I)-1,2-dihydropyridin-2-on; 3-(1 -benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on; 3-(1-benzoyl-5-[(5-chlorthiophen-2- yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(1 -benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(1 -benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 - (th i ophen-3-y I methy I)-1,2-dihydropyridin-2-on; 3-(1 -benzoyl-5-[(5-chlorthiophen-2- yl)methyl]amino-1 H-pyrazol-3-yl)-1-benzyl-1,2-dihydropyridin-2-on; 3-(1-benzoyl-5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl)-1 -methyl-1,2-dihydropyridin-2-on; 3- (5-[(4-fluorphenyl)methyl]amino-1-[(furan-2-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1-(2-phenylethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(2,2- dimethylpropanoyl)-1H-pyrazol-3-yl)-1-(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1-(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2- dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(naphthalen-1 -ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl )-1 H-pyrazol-3-yl)-1-(naphthalen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2- dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(py rid i n-3-y I m ethy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1H-pyrazol-3-yl)-1-(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2- dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl )-1 H-pyrazol-3-yl)-1-(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl )-1 H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)-2-oxoethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 -(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -methyl-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino- 1-(3-hydroxy-2,2-dimethylpropanoyl)-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-hydroxy-2,2-dimethylpropanoyl)-1H-pyrazol-3-yl)-1-(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(3- hydroxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(furan-2-ylmethyl)-1,2-d i hyd ropy ri d i n-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(3-hydroxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(pyrid i n-3-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(3-hydroxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy- 2.2- dimethylpropanoyl)-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(3-methoxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)- 1.2- dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2- dimethylpropanoyl)-1H-pyrazol-3-yl)-1-(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2-dimethylpropanoyl)~,1H-pyrazol-3-yl)-1-(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(3-methoxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(pyridazin-3-ylmethyl)-1,2- dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2-dimethylpropanoyl)-1H-pyrazol-3-yl)-1-(pyridin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(py rid i n-4-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2-dimethylpropanoyl)-1H-pyrazol-3-yl)-1-(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy-2,2-dimethylpropanoyl)-1H-pyrazol-3-yl)-1-(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 -(3-methoxy-2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-1 -(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(3-methoxy- 2.2- dimethylpropanoyl)-1 H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol -3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2,3-dihydro-1,4- benzodioxin-5-yl)carbonyl]-1 H-pyrazol -3-yI)-1 -(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol -3-y I)-1 -(furan-3-yl-methyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyrid i n-3-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyrid i n-4-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 -[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3H-pyrazol-3-yl)- 1- (pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(thiophen- 2- ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2,3- dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol -3-y I)-1 -(thiophen-3-ylmethyl)-1,2- dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol -3-y I)-1 -[2(morpholin-4-yl)ethyl]-1,2-d i hyd ropy rid i n-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2,3-dihydro-1,4-benzodioxin-5-yl)carbonyl]-1 H-pyrazol -3-yI)-1 -methyl-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1 H-pyrazol -3-yl)-1,2-di hydropyridi n-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4- dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-3-ylmethyl)- 1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(py rid i n-4-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-(thiophen-2-ylmethyl)- 1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2,4-dimethoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1,2-dihydropyridin-2-on;3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2- methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-(2-phenylethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-(naphthalen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyridazin-3-ylmethyl)-1,2-d i hyd ropyrid i n-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2- methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on;3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1 -(thiophen-2-ylmethyl)-1,2-d i hyd ropy rid i n-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino- 1-[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)-2-oxoethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2- methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-1-methyl-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(3-methyloxetan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1-methyl-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(furan-2-yl methyl )-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol -3-y I)-1 -(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(4-methyloxan-4-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(4-methyloxan-4-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(py rid i n-3-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino- 1-[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-pyrazol-3-yl)-1-(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5- chlorthiophen-2-yl)methyl]amino-1 -[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(4-methyloxan-4-yl)carbonyl]-1 H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)ethyl]- 1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-2-yl)carbonyl]-1H-pyrazol-3-yl)-1-(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(furan-2-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on;3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyridin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyrid i n-4-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-2-yl)carbonyl]-1H-pyrazol-3-yl)-1-(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(2-phenylethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(naphthalen-1 -ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(naphthalen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -[2-(morpholin-4-yl)-2-oxoethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5- chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(furan-2 -ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5- chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(py rid i n-2-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5- chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(pyridin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen- 2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(py rid i n-4-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5- chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1- (pyrimidin-2- ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen- 2-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-2-yl)carbonyl]-1 H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyrid i n-2-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(py rid i n-3-y I m ethy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(thiophen-3-yl)carbonyl]-1H-pyrazol-3-yl)-1-(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(thiophen-3-yl)carbonyl]-1 H-pyrazol-3-yl)-1 -[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[2-(morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1,2-d i hyd ropy ri d i n-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(2-methoxyethoxy)phenyl]carbonyl-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4- (morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[4-(morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4- (morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1 -(furan-2-ylmethyl)-1,2-d i hyd ropy rid i n-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[4-(morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1 -(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1 H- pyrazol-3-yl)-1 -(py rid i n-3-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 -[4-(morpholin-4-yl)pheny1 ]carbony1 -1 H-pyrazol-3-yl)-1 -(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1 H-pyrazo1 -3-y I)-1 -(pyrimidin-2-ylmethy1 )-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1 H-pyrazol-3-yl)-1-(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1H-pyrazol-3-yl)-1-(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[4-(morpholin-4-yl)phenyl]carbonyl-1 H-pgrazo1 -3-y I)-1 -[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(1 H-1,2,3,4-tetrazol-5-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(2-methoxyethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-(2-phenylethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-(furan-2 -ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2- yl)methyl]amino-1 H-pyrazol-3-yl)-1-(naphthalen-1-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(naphthalen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-(pyridazin- 3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl)-1-(pyridin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(py rid i n-4-y I methy I)-1,2-dihydropyridin-2-on; 3-(5-[(5- chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-(thiophen- 2- ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -[2-(morpholin-4-yl)-2-oxoethyl]-1,2-dihydropyridin-2-on; 3- (5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-[2-(morpholin-4-yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1 -[2-(py rid i n- 2- yl)ethyl]-1,2-dihydropyridin-2-on; 3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl)-1-methyl-1,2-dihydropyridin-2-on; 3-[5-(benzylamino)-1-[(furan-2-yl)carbonyl]-1 H-pyrazol- 3- yl]-1,2-dihydropyridin-2-on; 3-[5-(benzylamino)-1 -[(furan-2-yl)carbonyl]-1H-pyrazol-3-yl]-1- (py rid i n-2-y I methy I)-1,2-dihydropyridin-2-on; 3-[5-(dimethylamino)-1 -[(furan-2-yl)carbonyl]-1H-pyrazol-3-yl]-1,2-dihydropyridin-2-on; 3-[5-(dimethylamino)-1-[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl]-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-aminophenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl-1,2-dihydropyridin-2-on; 3-1-[(2- chlorphenyl)carbonyl]_,5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-(2- methoxyethyl)-1,2-dihydropyridin-2-on; 3-1 -[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-(furan-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-(furan-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-(pyridazin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-(pyridin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl-1-(pyridin-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-(pyridin-4-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2- yl)methyl]amino-1H-pyrazol-3-yl-1-(pyrimidin-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-(thiophen-2-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl-1-(thiophen-3-ylmethyl)-1,2-dihydropyridin-2-on; 3-1-[(2-chlorphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-[2-(morpholin- 4- yl)ethyl]-1,2-dihydropyridin-2-on; 3-1-[(4-tert-butylphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl-1,2-dihydropyridin-2-on; 3-1-[(4-tert-butylphenyl)carbonyl]-5-[(5-chlorthiophen-2-yl)methyl]amino-1 H-pyrazol-3-yl-1-methyl-1,2-dihydropyridin-2-on; 3- 5- amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl-1,2-dihydropyridin-2-on; 3-5-amino-1 -[(furan-2-yl)carbonyl]-1 H-pyrazol-3-yl-1 -(py rid i n-2-y I methy I)-1,2-dihydropyridin-2-on; ethyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-(2,2-dimethylpropanoyl)-1H-pyrazol-3-yl)-2-oxo- 1,2-d i hyd ropy rid i n-1 -yljacetat; ethyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -[(2- methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridin-1-yl]acetat; ethyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(furan-3-yl)carbonyl]-1H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridin-1 -yljacetat; ethyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl)-2-oxo-1,2-d i hyd ropy ri d i n-1 -yljacetat; tert-butyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 -(2,2-dimethylpropanoyl)-1 H-pyrazol-3-yl)-2-oxo-l,2-dihydropyiidin-1-yl]acetat; tert-butyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1-[(2-methoxyphenyl)carbonyl]-1 H-pyrazol-3-yl)-2-oxo-1,2-d i hyd ropyrid i n-1 -yljacetat; tert-butyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1 - [(furan-3-yl)carbonyl]-1 H-pyrazol-3-yl)-2-oxo-1,2-[hydropyridin-1-yl]acetat; tert-butyl-2-[3-(5-[(5-chlorthiophen-2-yl)methyl]amino-1H-pyrazol-3-yl)-2-oxo-1,2-dihydropyridin-1-yl]acetat og 1-[(5-[(5-chlorthiophen-2-yl)methyl]amino-3-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)-1 H-pyrazol-1-yl)carbonyl]cyclopropylmethyl 1-(hydroxymethyl)cyclopropan-1-carboxylat.
15. Farmaceutisk sammensætning, der omfatter en forbindelse ifølge et hvilket som helst af kravene 1 til 14, og en farmaceutisk acceptabel excipiens.
16. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 1-14, hvor forbindelsen er til anvendelse i behandling af en thrombotisk forstyrrelse; eventuelt hvor den thrombotiske forstyrrelser er eller flere valgt fra gruppen bestående af akut koronart syndrom, venethromboembolisme, arteriel thromboembolisme, kardiogen thromboembolisme, dissemineret intravaskulær koagulation og en tilstand, der involverer en blodpropthrombe.
17. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 1-14, hvor sygdommen eller forstyrrelsen er én eller flere valgt fra gruppen bestående af fibrose, Alzheimers sygdom, multipel sklerose, smerte og cancer.
18. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 1-14, hvor forbindelsen virker ved hæmning af thrombin.
19. Forbindelse til anvendelse ifølge et hvilket som helst af kravene 1-14, hvor sygdommen eller forstyrrelsen er en kallikrein-relateret forstyrrelse, hvor den kallikrein-relaterede forstyrrelse er én eller flere valgt fra gruppen bestående af en thrombotisk sygdom, en fibrinotytisk sygdom, en cancertype, en inflammatorisk tilstand, en dermatologisk tilstand og en ophthalmisk sygdom.
20. Forbindelse til anvendelse ifølge krav 19, hvor de ophthalmiske sygdom er en eller flere valgt fra gruppen bestående af diabetisk makulaødem, aldersrelateret makuladegeneration, og diabetisk retinopati; eller hvor cancertypen er én eller flere valgt fra gruppen bestående af cervical-, testis og ikke-småcellet lungeadenokarcinom; eller hvor den inflammatoriske tilstand er én eller flere valgt fra gruppen bestående af sepsis, inflammatorisk tarmsygdom, systemisk inflammatorisk responssyndrom, arveligt angioødem og rheumatoid arthritis; eller hvor den dermatologisk tilstand er én eller flere valgt fra gruppen bestående af atopisk dermatitis, psoriasis og Netherton syndrom.
21. Forbindelse til anvendelse ifølge krav 19, hvor forbindelsen virker ved hæmning af kallikrein, fortrinsvis hvor forbindelsen virker ved hæmning af vævskallikrein og/eller plasmakallikrein.
22. Forbindelse til anvendelse ifølge krav 20, hvor den kallikrein-relaterede forstyrrelse er en ophthalmisk sygdom, og hvor forbindelsen eller den farmaceutiske sammensætning administreres oralt, i form af en ophthalmisk sammesætning anvendt topisk i øjet eller via intravitreal injektion, fortrinsvis hvor den ophthalmiske sammensætning er i form af øjendråber.
23. Forbindelse til anvendelse ifølge et hvilket som helst foregående krav, hvor behandlingen haren profylaktisk virkning.
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