DK2280696T5 - Modulatorer af prostacyclin (PG12)-receptoren til anvendelse til behandling af lidelser relateret til denne - Google Patents

Modulatorer af prostacyclin (PG12)-receptoren til anvendelse til behandling af lidelser relateret til denne Download PDF

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DK2280696T5
DK2280696T5 DK09721284.9T DK09721284T DK2280696T5 DK 2280696 T5 DK2280696 T5 DK 2280696T5 DK 09721284 T DK09721284 T DK 09721284T DK 2280696 T5 DK2280696 T5 DK 2280696T5
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compound
methyl
methoxy
cyclohexyl
fluorophenyl
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DK09721284.9T
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DK2280696T3 (da
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Thuy-Anh Tran
Weichao Chen
Bryan A Kramer
Abu J M Sadeque
Hanna L Shyfryna
Young-Jun Shin
Pureza Vallar
Ning Zou
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Arena Pharm Inc
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Claims (51)

1
1. Forbindelse udvalgt blandt forbindelser med formlen (Xllla) og farmaceutisk acceptable salte, solvater og hydrater deraf:
hvor: R1 og R2 hver især uafhængigt er udvalgt blandt: H, CrC6-alkyl, aryl og hete-roaryl; hvor CrC6-alkyl, aryl og heteroaryl hver især er eventuelt substitueret med en eller to substituenter ufadvalgt blandt: CrC6-alkoxy, CrC6-alkyl, aryl, CrC6-haloalkoxy, CrC6-haloalkyl og halogen; X er O eller NR3; R3 er udvalgt blandt H og CrC6-alkyl; og Q er udvalgt blandt: OH, -NHCH2CH2SO3H, 1-carboxyethylamino, 1-carboxy- 4-guanidinobutylamino, 3-amino-1 -carboxy-3-oxopropylamino, 1,2-dicarboxy-ethylamino, 1 -carboxy-2-mercaptoethylamino, 4-amino-1 -carboxy-4-oxobutyl-amino, 3-carboxy-1-carboxylatopropylamino, carboxymethylamino, 1-carb-oxy-2-(1 /-/-imidazol-4-yl)ethylamino, 1-carboxy-2-methylbutylamino, 1-carb-oxy-3-methylbutylamino, 5-amino-1 -carboxypentylamino, 1 -carboxy-3-(me-thylthio)propylamino, 1 -carboxy-2-phenylethylamino, 2-carboxypyrrolidin-1 -yl, 1 -carboxy-2-hydroxyethylamino, 1 -carboxy-2-hydroxypropylamino, 1 -carb-oxy-2-(1 /-/-indol-3-yl)ethylamino, 1 -carboxy-2-(4-hydroxyphenyl)ethylamino og 1 -carboxy-2-methylpropylamino.
2. Forbindelse ifølge krav 1, hvor R1 og R2 hver især uafhængigt er udvalgt blandt: H, CrC6-alkyl, aryl og heteroaryl; hvor CrC6-alkyl, aryl og heteroaryl hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: methoxy, ethoxy, methyl, phenyl, trifluormethyl, trifluormethoxy, fluor og chlor.
3. Forbindelse ifølge krav 1, hvor R1 og R2 hver især uafhængigt er udvalgt blandt: H, methyl, phenyl, pyrazinyl, pyridinyl og thiazolyl; hvor methyl, phe- 2 nyl, pyrazinyl, pyridinyl og thiazolyl hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: methoxy, ethoxy, methyl, phenyl, trifluormethyl, trifluormethoxy, fluor og chlor.
4. Forbindelse ifølge krav 1, hvor R1 og R2 hver især uafhængigt er udvalgt blandt: H, diphenylmethyl, 2,3-difluorphenyl, 2-fluor-3-methoxyphenyl, 2-fluor-phenyl, 2-fluorpyridin-4-yl, 2-methoxyphenyl, 3-(trifluormethoxy)phenyl, 3,4-difluorphenyl, 3,5-difluorphenyl, 3,5-dimethylphenyl, 3-chlor-2-fluorphenyl, 3-chlor-4-fluorphenyl, 3-chlor-5-fluorphenyl, 3-chlorphenyl; 3-fluor-4-methylphe-nyl, 3-fluorphenyl, 3-methoxyphenyl, 3-tolyl, 3-(trifluormethyl)phenyl, 4-(tri-fluormethoxy)phenyl, 4-chlor-3-fluorphenyl, 4-chlorphenyl, 4-ethoxyphenyl, 4-fluorphenyl, 4-methoxy-2-methylphenyl, 4-methoxyphenyl, 4-tolyl, 5-(trifluor-methyl)pyridin-2-yl, 5-chlorpyridin-2-yl, 5-fluorpyridin-2-yl, 5-fluorpyridin-3-yl, 5-methoxypyridin-3-yl, 5-methylpyridin-3-yl, 5-methylthiazol-2-yl, 5-methyl-thiophen-2-yl, 6-fluorpyridin-3-yl, methyl, phenyl, n-propyl, pyrazin-2-yl, pyri-din-2-yl og pyridin-3-yl.
5. Forbindelse ifølge krav 1, hvor: R1 er udvalgt blandt: CrC6-alkyl, aryl og heteroaryl; hvor hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: CrC6-alkoxy, C-i-Ce-alkyl, aryl, CrC6-haloalkoxy, CrC6-haloalkyl og halogen; og R2 er udvalgt blandt: H, CrC6-alkyl og aryl; hvor nævnte aryl er eventuelt substitueret med en eller to substituenter udvalgt blandt: CrC6-alkyl og halogen.
6. Forbindelse ifølge krav 5, hvor: R1 er udvalgt blandt: CrC6-alkyl, aryl og heteroaryl; hvor hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: methoxy, ethoxy, methyl, phenyl, trifluormethyl, trifluormethoxy, fluor og chlor; og R2 er udvalgt blandt: H, CrC6-alkyl og aryl; hvor nævnte aryl er eventuelt substitueret med en eller to substituenter udvalgt blandt: methyl og fluor.
7. Forbindelse ifølge krav 6, hvor: R1 er udvalgt blandt: diphenylmethyl, 2,3-difluorphenyl, 2-fluor-3-methoxy-phenyl, 2-fluorphenyl, 2-fluorpyridin-4-yl, 2-methoxyphenyl, 3-(trifluormeth-oxy)phenyl, 3,4-difluorphenyl, 3,5-difluorphenyl, 3,5-dimethylphenyl, 3-chlor- 3 2-fluorphenyl, 3-chlor-4-fluorphenyl, 3-chlor-5-fluorphenyl, 3-chlorphenyl, 3-fluor-4-methylphenyl, 3-fluorphenyl, 3-methoxyphenyl, 3-tolyl, 3-(trifluormeth-yl)phenyl, 4-(trifluormethoxy)phenyl, 4-chlor-3-fluorphenyl, 4-chlorphenyl, 4-ethoxyphenyl, 4-fluorphenyl, 4-methoxy-2-methylphenyl, 4-methoxyphenyl, 4-tolyl, 5-(trifluormethyl)pyridin-2-yl, 5-chlorpyridin-2-yl, 5-fluorpyridin-2-yl, 5-fluorpyridin-3-yl, 5-methoxypyridin-3-yl, 5-methylpyridin-3-yl, 5-methylthiazol-2-yl, 5-methylthiophen-2-yl, 6-fluorpyridin-3-yl, phenyl, pyrazin-2-yl, pyridin-2-yl og pyridin-3-yl; og R2 er udvalgt blandt: H, methyl, n-propyl, phenyl, 3-tolyl, 4-tolyl, 3-fluorphenyl og 4-fluorphenyl.
8. Forbindelse ifølge et af kravene 1 til 7, hvor X er O.
9. Forbindelse ifølge et af kravene 1 til 7, hvor X er NR3.
10. Forbindelse ifølge krav 9, hvor R3 er H.
11. Forbindelse ifølge krav 9, hvor R3 er CrC6-alkyl.
12. Forbindelse ifølge krav 9, hvor R3 er methyl.
13. Forbindelse ifølge et af kravene 1 til 12, hvor Q er OFI.
14. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Xlllk) og farmaceutisk acceptable salte, solvater og hydrater deraf:
hvor: R1 og R2 hver især uafhængigt er udvalgt blandt: H, CrC6-alkyl, aryl og hete-roaryl; hvor CrC6-alkyl, aryl og heteroaryl hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: CrC6-alkoxy, CrC6-alkyl, aryl, C-i-Ce-haloalkoxy, CrC6-haloalkyl og halogen; og 4 Q er udvalgt blandt: OH, -NHCH2CH2SO3H, 1-carboxyethylamino, 1-carboxy-4-guanidinobutylamino, 3-amino-1 -carboxy-3-oxopropylamino, 1,2-dicarboxy-ethylamino, 1 -carboxy-2-mercaptoethylamino, 4-amino-1 -carboxy-4-oxobutyl-amino, 3-carboxy-1-carboxylatopropylamino, carboxymethylamino, 1-carb-oxy-2-(1 /-/-imidazol-4-yl)ethylamino, 1 -carboxy-2-methylbutylamino, 1 -carb-oxy-3-methylbutylamino, 5-amino-1 -carboxypentylamino, 1 -carboxy-3-(me-thylthio)propylamino, 1 -carboxy-2-phenylethylamino, 2-carboxypyrrolidin-1 -yl, 1 -carboxy-2-hydroxyethylamino, 1 -carboxy-2-hydroxypropylamino, 1 -carb-oxy-2-(1 /-/-indol-3-yl)ethylamino, 1 -carboxy-2-(4-hydroxyphenyl)ethylamino og 1 -carboxy-2-methylpropylamino.
15. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Xlllk)
alte, solvater og hydrater deraf: (Xnik) hvor: R1 er udvalgt blandt: diphenylmethyl, 2,3-difluorphenyl, 2-fluor-3-methoxy-phenyl, 2-fluorphenyl, 2-fluorpyridin-4-yl, 2-methoxyphenyl, 3-(trifluormeth-oxy)phenyl, 3,4-difluorphenyl, 3,5-difluorphenyl, 3,5-dimethylphenyl, 3-chlor-2-fluorphenyl, 3-chlor-4-fluorphenyl, 3-chlor-5-fluorphenyl, 3-chlorphenyl, 3-fluor-4-methylphenyl, 3-fluorphenyl, 3-methoxyphenyl, 3-tolyl, 3-(trifluorme-thyl)phenyl, 4-(trifluormethoxy)phenyl, 4-chlor-3-fluorphenyl, 4-chlorphenyl, 4-ethoxyphenyl, 4-fluorphenyl, 4-methoxy-2-methylphenyl, 4-methoxyphenyl, 4-tolyl, 5-(trifluormethyl)pyridin-2-yl, 5-chlorpyridin-2-yl, 5-fluorpyridin-2-yl, 5-fluorpyridin-3-yl, 5-methoxypyridin-3-yl, 5-methylpyridin-3-yl, 5-methylthiazol-2-yl, 5-methylthiophen-2-yl, 6-fluorpyridin-3-yl, phenyl, pyrazin-2-yl, pyridin-2-yl og pyridin-3-yl; R2 er udvalgt blandt: H, methyl, n-propyl, phenyl, 3-tolyl, 4-tolyl, 3-fluorphenyl og 4-fluorphenyl; og Q er udvalgt blandt: OH, -NHCH2CH2S03H og carboxymethylamino.
16. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Xlllm) og farmaceutisk acceptable salte, solvater og hydrater deraf: 5
hvor: R1 og R2 hver især uafhængigt er udvalgt blandt: H, Ci-C6-alkyl, aryl og hete-roaryl; hvor CrC6-alkyl, aryl og heteroaryl hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: CrC6-alkoxy, CrC6-alkyl, aryl, CrC6-haloalkoxy, CrC6-haloalkyl og halogen; og Q er udvalgt blandt: OH, -NHCH2CH2S03H, 1-carboxyethylamino, 1-carboxy-4-guanidinobutylamino, 3-amino-1 -carboxy-3-oxopropylamino, 1,2-dicarboxy-ethylamino, 1 -carboxy-2-mercaptoethylamino, 4-amino-1 -carboxy-4-oxobutyl-amino, 3-carboxy-1-carboxylatopropylamino, carboxymethylamino, 1-carb-oxy-2-(1 /-/-imidazol-4-yl)ethylamino, 1-carboxy-2-methylbutylamino, 1-carb-oxy-3-methylbutylamino, 5-amino-1 -carboxypentylamino, 1 -carboxy-3-(me-thylthio)propylamino, 1 -carboxy-2-phenylethylamino, 2-carboxypyrrolidin-1 -yl, 1 -carboxy-2-hydroxyethylamino, 1 -carboxy-2-hydroxypropylamino, 1 -carb-oxy-2-(1 /-/-indol-3-yl)ethylamino, 1 -carboxy-2-(4-hydroxyphenyl)ethylamino og 1 -carboxy-2-methylpropylamino.
17. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Xlllm) og farmaceutisk
acceptable salte, solvater og hydrater deraf: (.Aiiim; hvor: R1 er udvalgt blandt: diphenylmethyl, 2,3-difluorphenyl, 2-fluor-3-methoxy-phenyl, 2-fluorphenyl, 2-fluorpyridin-4-yl, 2-methoxyphenyl, 3-(trifluorme-thoxy)phenyl, 3,4-difluorphenyl, 3,5-difluorphenyl, 3,5-dimethylphenyl, 3-chlor-2-fluorphenyl, 3-chlor-4-fluorphenyl, 3-chlor-5-fluorphenyl, 3-chlorphe-nyl, 3-fluor-4-methylphenyl, 3-fluorphenyl, 3-methoxyphenyl, 3-tolyl, 3-(tri-fluormethyl)phenyl, 4-(trifluormethoxy)phenyl, 4-chlor-3-fluorphenyl, 4-chlor- 6 phenyl, 4-ethoxyphenyl, 4-fluorphenyl, 4-methoxy-2-methylphenyl, 4-meth-oxyphenyl, 4-tolyl, 5-(trifluormethyl)pyridin-2-yl, 5-chlorpyridin-2-yl, 5-fluor-pyridin-2-yl, 5-fluorpyridin-3-yl, 5-methoxypyridin-3-yl, 5-methylpyridin-3-yl, 5-methylthiazol-2-yl, 5-methylthiophen-2-yl, 6-fluorpyridin-3-yl, phenyl, pyrazin-2-yl, pyridin-2-yl og pyridin-3-yl; R2 er udvalgt blandt: H, methyl, n-propyl, phenyl, 3-tolyl, 4-tolyl, 3-fluorphenyl og 4-fluorphenyl; og Q er udvalgt blandt: OH, -NHCH2CH2S03H og carboxymethylamino.
18. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Ik) og farmaceutisk acceptable salte, solvater og hydrater deraf:
hvor: R1 og R2 hver især uafhængigt er udvalgt blandt: H, CrC6-alkyl, aryl og hete-roaryl; hvor CrC6-alkyl, aryl og heteroaryl hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: CrC6-alkoxy, CrC6-alkyl, aryl, C-i-Ce-haloalkoxy, CrC6-haloalkyl og halogen.
19. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Ik) og farmaceutisk acceptable salte, solvater og hydrater deraf:
hvor: R1 er udvalgt blandt: diphenylmethyl, 2,3-difluorphenyl, 2-fluor-3-methoxy-phenyl, 2-fluorphenyl, 2-fluorpyridin-4-yl, 2-methoxyphenyl, 3-(trifluormeth-oxy)phenyl, 3,4-difluorphenyl, 3,5-difluorphenyl, 3,5-dimethylphenyl, 3-chlor-2-fluorphenyl, 3-chlor-4-fluorphenyl, 3-chlor-5-fluorphenyl, 3-chlorphenyl, 3- 7 fluor-4-methylphenyl, 3-fluorphenyl, 3-methoxyphenyl, 3-tolyl, 3-(trifluor-methyl)phenyl, 4-(trifluormethoxy)phenyl, 4-chlor-3-fluorphenyl, 4-chlorphe-nyl, 4-ethoxyphenyl, 4-fluorphenyl, 4-methoxy-2-methylphenyl, 4-methoxy-phenyl, 4-tolyl, 5-(trifluormethyl)pyridin-2-yl, 5-chlorpyridin-2-yl, 5-fluorpyridin-2-yl, 5-fluorpyridin-3-yl, 5-methoxypyridin-3-yl, 5-methylpyridin-3-yl, 5-methyl-thiazol-2-yl, 5-methylthiophen-2-yl, 6-fluorpyridin-3-yl, phenyl, pyrazin-2-yl, pyridin-2-yl og pyridin-3-yl; og R2 er udvalgt blandt: H, methyl, n-propyl, phenyl, 3-tolyl, 4-tolyl, 3-fluorphenyl og 4-fluorphenyl.
20. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Im) og farmaceutisk acceptable salte, solvater og hydrater deraf:
hvor: R1 og R2 hver især uafhængigt er udvalgt blandt: H, CrC6-alkyl, aryl og hete-roaryl; hvor CrC6-alkyl, aryl og heteroaryl hver især er eventuelt substitueret med en eller to substituenter udvalgt blandt: CrC6-alkoxy, CrC6-alkyl, aryl, C-i-Ce-haloalkoxy, CrC6-haloalkyl og halogen.
21. Forbindelse ifølge krav 1, udvalgt blandt forbindelser med formlen (Im) og farmaceutisk acceptable salte, solvater og hydrater deraf: hvor:
R1 er udvalgt blandt: diphenylmethyl, 2,3-difluorphenyl, 2-fluor-3-methoxy-phenyl, 2-fluorphenyl, 2-fluorpyridin-4-yl, 2-methoxyphenyl, 3-(trifluormeth-oxy)phenyl, 3,4-difluorphenyl, 3,5-difluorphenyl, 3,5-dimethylphenyl, 3-chlor- 8 2-fluorphenyl, 3-chlor-4-fluorphenyl, 3-chlor-5-fluorphenyl, 3-chlorphenyl, 3-fluor-4-methylphenyl, 3-fluorphenyl, 3-methoxyphenyl, 3-tolyl, 3-(trifluor-methyl)phenyl, 4-(trifluormethoxy)phenyl, 4-chlor-3-fluorphenyl, 4-chlor-phenyl, 4-ethoxyphenyl, 4-fluorphenyl, 4-methoxy-2-methylphenyl, 4-meth-oxyphenyl, 4-tolyl, 5-(trifluormethyl)pyridin-2-yl, 5-chlorpyridin-2-yl, 5-fluorpy-ridin-2-yl, 5-fluorpyridin-3-yl, 5-methoxypyridin-3-yl, 5-methylpyridin-3-yl, 5-methylthiazol-2-yl, 5-methylthiophen-2-yl, 6-fluorpyridin-3-yl, phenyl, pyrazin-2-yl, pyridin-2-yl og pyridin-3-yl; og R2 er udvalgt blandt: H, methyl, n-propyl, phenyl, 3-tolyl, 4-tolyl, 3-fluorphenyl og 4-fluorphenyl.
22. Forbindelse ifølge krav 1 udvalgt blandt de følgende forbindelser og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-((3-benzhydrylureido)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 1); 2-(((1 r,4r)-4-((3,3-diphenylureido)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 2); 2-(((1 r,4r)-4-((3-(3-fluorphenyl)-3-phenylureido)methyl)cyclohexyl)methoxy) eddikesyre (Forbindelse 3); 2-(((1 r,4r)-4-((1-methyl-3,3-diphenylureido)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 4); 2-(((1 r,4r)-4-((diphenylcarbamoyloxy)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 5); 2-(((1 r,4r)-4-((3-(3-chlorphenyl)-3-phenylureido)methyl)cyclohexyl)methoxy) eddikesyre (Forbindelse 6); 2-(((1 s,4s)-4-((diphenylcarbamoyloxy)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 7); 9 2-(((1 r,4r)-4-((3-(4-fluorphenyl)-3-phenylureido)methyl)cyclohexyl)methoxy) eddikesyre (Forbindelse 8); 2-(((1 s,4s)-4-((3,3-diphenylureido)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 9); 2-(((1 r,4r)-4-((3-(2-fluorphenyl)-3-phenylureido)methyl)cyclohexyl)methoxy) eddikesyre (Forbindelse 10); 2-(((1 r,4r)-4-((3-(4-chlorphenyl)-3-phenylureido)methyl)cyclohexyl)methoxy) eddikesyre (Forbindelse 11); 2-(((1 r,4r)-4-((3-phenyl-3-m-tolylureido)methyl)cyclohexyl)methoxy)eddike-syre (Forbindelse 12); 2-(((1 r,4r)-4-((3-phenyl-3-p-tolylureido)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 13); 2-(((1 r,4r)-4-(((3-methoxyphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 14); 2-(((1 r,4/)-4-((3,3-di p-tolylureido)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 15); 2-(((1 r,4/)-4-((3,3-di m-tolylureido)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 16); 2-(((1 r,4/)-4-((3-(3-methoxyphenyl)-3-phenylureido)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 17); 2-(((1 r,4/)-4-((3-(4-methoxyphenyl)-3-phenylureido)methyl)cyclohexyl)me-thoxy)eddikesyre (Forbindelse 18); 2-(((1 r,4/)-4-((3-(4-methoxy-2-methylphenyl)-3-phenylureido)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 19); 10 2-(((1 r,4r)-4-((3-phenyl-3-(3-(trifluormethyl)phenyl)ureido)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 20); 2-(((1 r,4r)-4-(((4-methoxyphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 21); 2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)me-thoxy)eddikesyre (Forbindelse 22); 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)me-thoxy)eddikesyre (Forbindelse 23); 2-(((1 s,4s)-4-(((4-methoxphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 24); 2-(((1 s,4s)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 25); 2-(((1 s,4s)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 26); 2-(((1 r,4r)-4-((phenyl(/r?-tolyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 27); 2-(((1 r,4r)-4-(((3-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 28); 2-(((1 r,4r)-4-((phenylcarbamoyloxy)methyl)cyclohexyl)methoxy)eddikesyre (Forbindelse 29); 2-(((1 s,4s)-4-(((3-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 30); 2-(((1 s,4s)-4-((phenyl(m-tolyl)carbamoyloxy)methyl)cyclohexyl)methoxy) eddikesyre (Forbindelse 31); 11 2-((((1 s,4s)-4-(((2-methoxyphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 32); 2-(((1 s,4s)-4-(((3-methoxyphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 33); 2-(((1 s,4s)-4-((phenyl(p-tolyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 34); 2-(((1 s,4s)-4-(((4-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 35); 2-(((1 r,4r)-4-(((4-chlor-3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 36); 2-(((1 r,4r)-4-(((3-chlor-4-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 37); 2-(((1 r,4r)-4-(((3-fluor-4-methylphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 38); 2-(((1 r, 4/)-4-(((3,5-difluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 39); 2-(((1 r,4r)-4-(((3,4-difluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 40); 2-(((1 r,4r)-4-(((4-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)me-thoxy)eddikesyre (Forbindelse 41); 2-(((1 r,4r)-4-((phenyl(p-tolyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 42); 2-(((1 r,4r)-4-((3-(2,3-difluorphenyl)-3-phenylureido)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 43); 12 2-(((1 r,4/)-4-((3-(3,5-difluorphenyl)-3-phenylureido)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 44); 2-(((1 r,4/)-4-((3-(3-chlor-2-fluorphenyl)-3-phenylureido)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 45); 2-(((1 /',4/)-4-(((3-chlor-5-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 46); 2-(((1 r,4/)-4-((3-(3-chlor-5-fluorphenyl)-3-phenylureido)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 47); 2-(((1/',4/)-4-((3-benzhydryl-3-methylureido)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 48); 2-(((1/',4/)-4-((phenyl(pyridin-3-yl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 49); 2-(((1 /',4/)-4-(((5-methylthiophen-2-yl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 50); 2-(((1 r,4/)-4-(((2,3-difluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 51); 2-(((1 r,4r)-4-((3-(4-chlor-3-fluorphenyl)-3-phenylureido)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 52); 2-(((1 r,4r)-4-((3-(2-fluor-3-methoxyphenyl)-3-phenylureido)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 53); 2-(((1 r,4/)-4-((3-(3,4-difluorphenyl)-3-phenylureido)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 54); 2-(((1 r,4/)-4-(((3-fluorphenyl)(4-methoxyphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 55); 13 2-(((1 r,4r)-4-(((4-chlorphenyl)(3-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 56); 2-(((1 r,4r)-4-(((3-fluorphenyl)(4-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 57); 2-(((1 r,4r)-4-(((3-chlorphenyl)(3-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 58); 2-(((1 r,4r)-4-(((3-fluorphenyl)(/77-tolyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 59); 2-(((1 r,4r)-4-(((4-chlor-3-fluorphenyl)(3-fluorphenyl)carbamoyloxy)methyl) cyclohexyl)methoxy)eddikesyre (Forbindelse 60); 2-(((1 r,4r)-4-(((3-chlor-4-fluorphenyl)(3-fluorphenyl)carbamoyloxy)methyl) cyclohexyl)methoxy)eddikesyre (Forbindelse 61); 2-(((1 /',4r)-4-(((3-fluor-4-methylphenyl)(3-fluorphenyl)carbamoyloxy)methyl) cyclohexyl)methoxy)eddikesyre (Forbindelse 62); 2-(((1 /',4f)-4-((phenyl(pyridin-2-yl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 63); 2-(((1 /',4r)-4-(((3,5-difluorphenyl)(3-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 64); 2-(((1 r,4r)-4-(((3,4-difluorphenyl)(3-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 65); 2-(((1 r,4r)-4-((bis(3-fluorphenyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 66); 2-(((1 r,4r)-4-(((3-fluorphenyl)(3-methoxyphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 67); 14 2-(((1 r,4r)-4-(((3,5-dimethylphenyl)(3-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 68); 2-(((1 r,4r)-4-(((3-fluorphenyl)(p-tolyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 69); 2-(((1 r,4r)-4-(((3-fluorphenyl)(6-fluorpyridin-3-yl)carbamoyloxy)methyl) cyclo-hexyl)methoxy)eddikesyre (Forbindelse 70); 2-(((1 r,4r)-4-(((3-fluorphenyl)(5-methylthiophen-2-yl)carbamoyloxy)methyl) cyclohexyl)methoxy)eddikesyre (Forbindelse 71); 2-(((1 r,4r)-4-(((4-ethoxyphenyl)(3-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 72); 2-(((1 r,4r)-4-(((3-fluorphenyl)(3-(trifluormethoxy)phenyl)carbamoyloxy)meth-yl)cyclohexyl)methoxy)eddikesyre (Forbindelse 73); 2-(((1 /',4r)-4-(((3-fluorphenyl)(pyridin-3-yl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 74); 2-(((1 /',4r)-4-(((3-fluorphenyl)(pyrazin-2-yl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 75); 2-(((1 /',4r)-4-(((4-chlorphenyl)(4-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 76); 2-(((1 r,4r)-4-(((4-fluorphenyl)(5-methylthiophen-2-yl)carbamoyloxy)methyl) cyclohexyl)methoxy)eddikesyre (Forbindelse 77); 2-(((1 r,4/)-4-(((3-chlorphenyl)(4-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 78); 2-(((1 r,4/)-4-(((4-fluorphenyl)(pyridin-3-yl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 79); 15 2-(((1 /',4r)-4-(((4-ethoxyphenyl)(4-fluorphenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 80); 2-(((1 r,4r)-4-(((4-fluorphenyl)(4-(trifluormethoxy)phenyl)carbamoyloxy)meth-yl)cyclohexyl)methoxy)eddikesyre (Forbindelse 81); 2-(((1 /',4r)-4-(((4-fluorphenyl)(/77-tolyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 82); 2-(((1 /',4r)-4-((bis(4-fluorphenyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 83); 2-(((1 /',4r)-4-(((6-fluorpyridin-3-yl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 84); 2-(((1 r,4r)-4-((phenyl(pyrazin-2-yl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 85); 2-(((1 /',4r)-4-((benzhydryl(methyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 86); 2-(((1 r,4/)-4-((3-benzhydryl-1,3-dimethylureido)methyl)cyclohexyl)methoxy) eddikesyre (Forbindelse 87); 2-(((1 r,4/)-4-(((4-ethoxyphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 88); 2-(((1 r,4/)-4-(((2-fluorpyridin-4-yl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 89); 2-(((1 r,4/)-4-(((5-methoxypyridin-3-yl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 90); 2-(((1 r,4/)-4-(((5-fluorpyridin-2-yl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 91); 16 2-(((1 r,4r)-4-((phenyl(5-(trifluormethyl)pyridin-2-yl)carbamoyloxy)meth-yl)cyclohexyl)methoxy)eddikesyre (Forbindelse 92); 2-(((1 r,4r)-4-(((5-methylpyridin-3-yl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 93); 2-(((1 r,4r)-4-(((5-chlorpyridin-2-yl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 94); 2-(((1 r,4r)-4-(((5-fluorpyridin-3-yl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 95); 2-(((1 r,4r)-4-((benzhydryl(propyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 96); og 2-(((1 r,4r)-4-(((5-methylthiazol-2-yl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 97).
23. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-((3-(3-methoxyphenyl)-3-phenylureido)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 17).
24. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 22).
25. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 23).
26. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 17 2-(((1 r,4r)-4-((phenyl(m-tolyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 27).
27. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-(((4-chlor-3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 36).
28. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-(((3,5-difluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 39).
29. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-(((4-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl)meth-oxy)eddikesyre (Forbindelse 41).
30. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-(((5-chlorpyridin-2-yl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 94).
31. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(((1 r,4r)-4-(((5-fluorpyridin-3-yl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)eddikesyre (Forbindelse 95).
32. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 2-(2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetamido)ethansulfonsyre (Forbindelse 99).
33. Forbindelse ifølge krav 1 udvalgt blandt den følgende forbindelse og farmaceutisk acceptable salte, solvater og hydrater deraf: 18 2-(2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetamido)eddikesyre (Forbindelse 100).
34. Salt ifølge krav 1 udvalgt blandt de følgende salte og farmaceutisk acceptable solvater og hydrater deraf: natrium 2-(((1 r,4r)-4-((diphenylcarbamoyloxy)methyl)cyclohexyl)meth-oxy)acetat; natrium 2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetat; natrium 2-(((1 r,4r)-4-(((4-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetat; natrium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetat; magnesium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetat; kalium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetat; og calcium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetat.
35. Salt ifølge krav 1 udvalgt blandt det følgende salt og farmaceutisk acceptable solvater og hydrater deraf: natrium 2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl) cyclohe-xyl)methoxy)acetat.
36. Solvat eller hydrat ifølge krav 1 udvalgt blandt de følgende solvater og hydrater: natrium 2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-h exyl) m et h oxy) acetat hyd rat; 19 natrium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl) cyclohexyl) methoxy)acetat hydrat; magnesium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl)cyclo-hexyl)methoxy)acetat isopropanolsolvat; kalium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl) cyclohexyl) methoxy)acetat isopropanolsolvat; og calcium 2-(((1 r,4r)-4-(((3-fluorphenyl)(phenyl)carbamoyloxy)methyl) cyclohexyl) methoxy)acetat isopropanolsolvat.
37. Krystallinsk form af forbindelsen ifølge krav 1, udvalgt blandt: natrium 2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl) cyclohe-xyl)methoxy)acetat.
38. Krystallinsk form af forbindelsen ifølge krav 1, udvalgt blandt: 2-(((1 r,4r)-4-(((4-chlorphenyl)(phenyl)carbamoyloxy)methyl)cyclohexyl) methoxy)eddikesyre (Forbindelse 22).
39. Farmaceutisk sammensætning omfattende: en forbindelse ifølge et af krav 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, eller en krystallinsk form ifølge krav 37 eller 38; og en farmaceutisk acceptabel bærer.
40. Fremgangsmåde til fremstilling af en sammensætning omfattende at blande: en forbindelse ifølge et af kravene 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, eller en krystallinsk form ifølge krav 37 eller 38; og en farmaceutisk acceptabel bærer.
41. Forbindelse ifølge et af kravene 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, en krystallinsk form ifølge krav 37 eller 38, til anvendelse ved en fremgangsmåde til behandling af en menneske- eller dyrekrop ved hjælp af terapi. 20
42. Forbindelse ifølge et af kravene 1 til 33, salt ifølge krav 34 eller 35, hydrat eller solvat ifølge krav 36, krystallinsk form ifølge krav 37 eller 38, til anvendelse ved en fremgangsmåde til modulering af aktiviteten af en PGI2-receptor.
43. Forbindelse ifølge et af kravene 1 til 33, salt ifølge krav 34 eller 35, hydrat eller solvat ifølge krav 36, krystallinsk form ifølge krav 37 eller 38, til anvendelse ved en fremgangsmåde til agonisering af en PGI2-receptor.
44. Forbindelse ifølge et af kravene 1 til 33, salt ifølge krav 34 eller 35, hydrat eller solvat ifølge krav 36, krystallinsk form ifølge krav 37 eller 38, til anvendelse ved en fremgangsmåde til behandling af PAFI.
45. Forbindelse ifølge et af kravene 1 til 33, salt ifølge krav 34 eller 35, hydrat eller solvat ifølge krav 36, krystallinsk form ifølge krav 37 eller 38, til anvendelse ved behandling af: idiopatisk PAFI; familiær PAFI; PAFI associeret med kollagen vaskulær sygdom udvalgt blandt: sklerodermi, CREST-syndrom, systemisk lupus erythematosus (SLE), reumatoid artritis, Takayasus arteritis, polymyositis og dermatomyositis; PAH associeret med en medfødt hjertesygdom udvalgt blandt: atrieseptum-defekt (ASD), ventrikelseptumdefekt (VSD) og patent ductus arteriosus i et individ; PAH associeret med portal hypertension; PAFI associeret med HlV-infektion; PAFI associeret med indtagelse af et medikament eller toxin; PAFI associeret med hereditær hæmoragisk teleangietaksi; PAH associeret med splenektomi; PAH associeret med væsentlig venøs eller kapillær indblanden; PAH associeret med pulmonal veno-okklusiv sygdom (PVOD); eller PAH associeret med pulmonal kapillær hemangiomatosis (PCH).
46. Forbindelse ifølge et af kravene 1 til 33, salt ifølge krav 34 eller 35, hydrat eller solvat ifølge krav 36, krystallinsk form ifølge krav 37 eller 38, til anvendelse ved behandling af en lidelse udvalgt blandt: pladeaggregation, koronar 21 arteriesygdom, myokardieinfarkt, transient iskæmisk anfald, angina, slagtilfælde, iskæmi-reperfusionsskade, restenose, atrieflimren, blodkoageldannel-se, aterosklerose, aterotrombose, astma, symptom på astma, en diabetes-relateret lidelse, diabetisk perifer neuropati, diabetisk nefropati, diabetisk re-tinopati, glaukom eller en anden øjensygdom med abnormt intraokkulært tryk, hypertension, inflammation, psoriasis, psoriasis artritis, reumatoid artri-tis, Crohns sygdom, afstødelse af transplantat, multipel sklerose, systemisk lupus erythematosus (SLE), colitis ulcerosa, iskæmi-reperfusionsskade, restenose, aterosklerose, acne, type 1-diabetes, type 2-diabetes, sepsis og kronisk obstruktiv lungesygdom (KOL).
47. Anvendelse af en forbindelse ifølge et af kravene 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, eller en krystallinsk form ifølge krav 37 eller 38, ved fremstilling af et medikament til modulering af aktiviteten af en PGI2-receptor.
48. Anvendelse af en forbindelse ifølge et af kravene 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, eller en krystallinsk form ifølge krav 37 eller 38, ved fremstilling af et medikament til agonisering af en PGI2-receptor.
49. Anvendelse af en forbindelse ifølge et af kravene 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, eller en krystallinsk form ifølge krav 37 eller 38, ved fremstilling af et medikament til behandling af PAH.
50. Anvendelse af en forbindelse ifølge et af kravene 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, eller en krystallinsk form ifølge krav 37 eller 38, ved fremstilling af et medikament til behandling af: idiopatisk PAH; familiær PAH; PAH associeret med en kollagen vaskulær sygdom udvalgt blandt: sklero-dermi, CREST-syndrom, systemisk lupus erythematosus (SLE), reumatoid artritis, Takayasus arteritis, polymyositis og dermatomyositis; 22 PAH associeret med en medfødt hjertesygdom udvalgt blandt: atrieseptum-defekt (ASD), ventrikelseptumdefekt (VSD) og patent ductus arteriosus i et individ; PAH associeret med portal hypertension; PAH associeret med HIV-infektion; PAH associeret med indtagelse af et medikament eller toxin; PAH associeret med hereditær hæmoragisk teleangietaksi; PAH associeret med splenektomi; PAH associeret med væsentlig venøs eller kapillær indblanden; PAH associeret med pulmonal veno-okklusiv sygdom (PVOD); eller PAH associeret med pulmonal kapillær hemangiomatosis (PCH) i et individ.
51. Anvendelse af en forbindelse ifølge et af kravene 1 til 33, et salt ifølge krav 34 eller 35, et hydrat eller solvat ifølge krav 36, eller en krystallinsk form ifølge krav 37 eller 38, til fremstilling af et medikament til behandling af en lidelse udvalgt blandt: pladeaggregation, koronar arteriesygdom, myokardie-infarkt, transient iskæmisk anfald, angina, slagtilfælde, iskæmi-reperfusions-skade, restenose, atrieflimren, blodkoageldannelse, aterosklerose, atero-trombose, astma, symptom på astma, en diabetes-relateret lidelse, diabetisk perifer neuropati, diabetisk nefropati, diabetisk retinopati, glaukom eller en anden øjensygdom med abnormt intraokkulært tryk, hypertension, inflammation, psoriasis, psoriasis artritis, reumatoid artritis, Crohns sygdom, afstødel-se af transplantat, multipel sklerose, systemisk lupus erythematosus (SLE), colitis ulcerosa, iskæmi-reperfusionsskade, restenose, aterosklerose, acne, type 1-diabetes, type 2-diabetes, sepsis og kronisk obstruktiv lungesygdom (KOL).
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Families Citing this family (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101898407B1 (ko) 2007-12-17 2018-09-12 유나이티드 세러퓨틱스 코오포레이션 레모둘린®의 활성 성분인 트레프로스티닐의 개선된 제조 방법
KR20220031743A (ko) * 2008-03-18 2022-03-11 아레나 파마슈티칼스, 인크. 프로스타시클린 （ｐｇｉ２） 수용체와 관련된 장애의 치료에 유용한 상기 수용체의 조절제
CA2744124C (en) 2008-11-26 2018-05-01 Arena Pharmaceuticals, Inc. Pyrazolyl substituted carbonic acid derivatives as modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto
PT2370413E (pt) 2008-12-08 2015-10-23 Arena Pharm Inc Moduladores do recetor da prostaciclina (pgi2) úteis para o tratamento de distúrbios relacionados com o mesmo
US20120225937A1 (en) * 2009-09-23 2012-09-06 Arena Pharmaceuticals, Inc. Crystalline forms and processes for the preparation of pg12 receptor agonists
JP6046034B2 (ja) 2010-06-03 2016-12-14 ユナイテッド セラピューティクス コーポレイション トレプロスチニルの製造
US8461393B2 (en) 2011-03-02 2013-06-11 United Therapeutics Corporation Synthesis of intermediate for treprostinil production
US10987322B2 (en) 2014-06-06 2021-04-27 Flexus Biosciences, Inc. Immunoregulatory agents
KR101890080B1 (ko) 2014-10-20 2018-09-20 유나이티드 쎄러퓨틱스 코포레이션 프로스타시클린 유도체 제조를 위한 중간체의 합성
JP6768646B2 (ja) 2014-10-23 2020-10-14 アリーナ ファーマシューティカルズ， インコーポレイテッド Ｐｇｉ２受容体に関連した状態の治療法
EP3215141A4 (en) 2014-11-05 2018-06-06 Flexus Biosciences, Inc. Immunoregulatory agents
UY36391A (es) 2014-11-05 2016-06-01 Flexus Biosciences Inc Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido1), sus métodos de síntesis y composiciones farmacèuticas que las contienen
UY36390A (es) 2014-11-05 2016-06-01 Flexus Biosciences Inc Compuestos moduladores de la enzima indolamina 2,3-dioxigenasa (ido), sus métodos de síntesis y composiciones farmacéuticas que los contienen
RU2632449C1 (ru) * 2016-04-26 2017-10-04 Государственное бюджетное образовательное учреждение высшего профессионального образования "Уральский государственный медицинский университет Министерства здравоохранения Российской Федерации" (ГБОУ ВПО УГМУ Минздрава России) Способ оптимизации лечения мужчин кардиотропной терапией и заместительной гормональной терапией при андрогенодефиците с артериальной гипертензией
EP3538154A1 (en) 2016-11-10 2019-09-18 Arena Pharmaceuticals, Inc. Methods of treating pah with combinations of ralinepag and other agents
RU2019121646A (ru) 2016-12-14 2021-01-15 Респира Терапьютикс, Инк. Способы и композиции для лечения легочной гипертензии и других заболеваний легких
KR102432505B1 (ko) * 2017-03-01 2022-08-12 아레나 파마슈티칼스, 인크. Pgi2-수용체 효능제를 포함하는 조성물 및 그의 제조 방법
MX2020000999A (es) * 2017-07-27 2020-07-22 Allergan Inc Agonistas del receptor de prostacyclin para reducir la grasa corporal.
US20200368190A1 (en) * 2017-08-07 2020-11-26 Arena Pharmaceuticals, Inc. Methods of treatment
EP3750879A4 (en) * 2018-02-07 2020-12-16 Medshine Discovery Inc. PROSTACYCLIN RECEPTOR AGONIST
JP7519909B2 (ja) * 2018-05-16 2024-07-22 アレーナ ファーマシューティカルズ，インク． Ｐｇｉ２－受容体アゴニストを含む組成物、およびその調製のためのプロセス
WO2020048299A1 (zh) * 2018-09-06 2020-03-12 广东东阳光药业有限公司 药物共晶体及其制备方法
CN110903219A (zh) * 2018-09-18 2020-03-24 广东东阳光药业有限公司 酰胺衍生物的盐及其制备方法
CN114213256A (zh) * 2021-12-27 2022-03-22 苏州久显新材料有限公司 一种二(4-联苯基)胺的制备方法
AU2023222747A1 (en) * 2022-02-15 2024-08-22 United Therapeutics Corporation Crystalline prostacyclin (ip) receptor agonist and uses thereof
US20240002334A1 (en) * 2022-03-17 2024-01-04 United Therapeutics Corporation Ralinepag prodrugs and uses thereof

Family Cites Families (39)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2945530A1 (de) * 1979-11-10 1981-06-04 Chemische Werke Hüls AG, 4370 Marl Harnstoffe mit cyclischen substituenten, ihre herstellung und verwendung als herbizide
JPS5686417A (en) * 1979-12-17 1981-07-14 Nissan Motor Contact discriminating circuit
JPH03160438A (ja) 1989-11-20 1991-07-10 Konica Corp ハロゲン化銀カラー写真感光材料
EP0442448A3 (en) 1990-02-13 1992-08-12 Bristol-Myers Squibb Company Heterocyclic carboxylic acids and esters
CA2085844A1 (en) 1991-12-27 1993-06-28 Nobuyuki Hamanaka Fused benzeneoxyacetic acid derivatives
JPH06329598A (ja) 1993-05-19 1994-11-29 Daicel Chem Ind Ltd エステルの製造方法
DE4318889A1 (de) 1993-06-07 1994-12-08 Bayer Ag Verfahren zur Herstellung von organischen Carbamaten
JP3160438B2 (ja) 1993-09-29 2001-04-25 株式会社東芝 交通流予測装置
WO1995024393A1 (en) 1994-03-10 1995-09-14 Fujisawa Pharmaceutical Co., Ltd. Naphthalene derivatives as prostaglandin i2 agonists
JPH11269138A (ja) 1998-03-20 1999-10-05 Mitsubishi Paper Mills Ltd 有機塩基発生剤
US6335459B1 (en) 1998-12-23 2002-01-01 Syntex (U.S.A.) Llc Aryl carboxylic acid and aryl tetrazole derivatives as IP receptor modulators
GB9908934D0 (en) 1999-04-19 1999-06-16 Rolic Ag Liquid crystalline compounds
EP1046631A1 (en) 1999-04-19 2000-10-25 Rolic AG Liquid crystalline compounds
US20040048844A1 (en) 1999-10-20 2004-03-11 Bristol-Myers Squibb Pharma Company Acylsemicarbazides as cyclin dependent kinase inhibitors useful as anti-cancer and anti-proliferative agents
AU5216801A (en) * 2000-03-16 2001-09-24 Hoffmann La Roche Carboxylic acid derivatives as ip antagonists
WO2002055484A1 (fr) 2001-01-12 2002-07-18 Takeda Chemical Industries, Ltd. Compose biaryle, procede de production de ce compose, et principe actif
AU2002240235B2 (en) * 2001-01-30 2006-07-06 Merck & Co., Inc. Acyl sulfamides for treatment of obesity, diabetes and lipid disorders
TWI316055B (da) * 2001-04-26 2009-10-21 Nippon Shinyaku Co Ltd
US20030144350A1 (en) 2001-07-20 2003-07-31 Adipogenix, Inc. Fat accumulation-modulation compounds
KR20040022238A (ko) 2001-08-09 2004-03-11 오노 야꾸힝 고교 가부시키가이샤 카르복실산 유도체 화합물 및 그 화합물을 유효성분으로서 함유하는 약제
TW200307539A (en) 2002-02-01 2003-12-16 Bristol Myers Squibb Co Cycloalkyl inhibitors of potassium channel function
TWI293715B (en) 2002-10-10 2008-02-21 Sipix Imaging Inc A method for inducing or enhancing the threshold of an electrophoretic display, an electrophoretic fluid and an electrophoretic display
CN1735598A (zh) * 2002-11-11 2006-02-15 拜耳医药保健股份公司 作为ip受体拮抗剂的苯基或杂芳基氨基烷烃衍生物
KR20050101200A (ko) 2003-02-10 2005-10-20 버텍스 파마슈티칼스 인코포레이티드 Ｎ-아릴 카밤산 에스테르를 할로-헤테로아릴과반응시킴으로써 ｎ-헤테로아릴-ｎ-아릴-아민을 제조하는방법 및 유사 방법
GB0317498D0 (en) * 2003-07-25 2003-08-27 Pfizer Ltd Compounds
BRPI0414630A (pt) * 2003-09-22 2006-11-07 Hoffmann La Roche derivados ciclohexìlicos substituìdos com aminoalquilamida
JP4402413B2 (ja) 2003-09-29 2010-01-20 財団法人２１あおもり産業総合支援センター Ｕ字型化合物およびこれを含む液晶組成物
US20060063930A1 (en) 2004-08-20 2006-03-23 Agoston Gregory E Compositions and methods comprising proteinase activated receptor antagonists
JP2006083085A (ja) 2004-09-15 2006-03-30 Kyowa Hakko Kogyo Co Ltd 二環性ピリミジン誘導体の製造法およびその合成中間体
JP4792731B2 (ja) 2004-11-12 2011-10-12 Ｄｉｃ株式会社 重合性液晶組成物及び当該組成物の硬化物
WO2007051255A1 (en) 2005-11-04 2007-05-10 The University Of Sydney Process for the preparation of compounds containing an azacyclic ring system
JP2007161867A (ja) 2005-12-14 2007-06-28 Toyo Ink Mfg Co Ltd インキ組成物
AU2007226673A1 (en) * 2006-03-10 2007-09-20 Jenrin Discovery Cannabinoid receptor antagonists/inverse agonists useful for treating obesity
JP2009536659A (ja) 2006-05-09 2009-10-15 ヘマクエスト・ファーマシューティカルズ，インコーポレーテッド 血液疾患の治療法
KR20220031743A (ko) * 2008-03-18 2022-03-11 아레나 파마슈티칼스, 인크. 프로스타시클린 （ｐｇｉ２） 수용체와 관련된 장애의 치료에 유용한 상기 수용체의 조절제
CA2744124C (en) 2008-11-26 2018-05-01 Arena Pharmaceuticals, Inc. Pyrazolyl substituted carbonic acid derivatives as modulators of the prostacyclin (pgi2) receptor useful for the treatment of disorders related thereto
PT2370413E (pt) 2008-12-08 2015-10-23 Arena Pharm Inc Moduladores do recetor da prostaciclina (pgi2) úteis para o tratamento de distúrbios relacionados com o mesmo
US20120225937A1 (en) 2009-09-23 2012-09-06 Arena Pharmaceuticals, Inc. Crystalline forms and processes for the preparation of pg12 receptor agonists
JP3160438U (ja) 2010-04-14 2010-06-24 孝枝 袴田 弦楽器演奏練習補助具

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