DK2940013T3 - Halogen-substitueret heterocyklisk forbindelse - Google Patents

Halogen-substitueret heterocyklisk forbindelse Download PDF

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DK2940013T3
DK2940013T3 DK13868493.1T DK13868493T DK2940013T3 DK 2940013 T3 DK2940013 T3 DK 2940013T3 DK 13868493 T DK13868493 T DK 13868493T DK 2940013 T3 DK2940013 T3 DK 2940013T3
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biphenyl
amino
carbonyl
ethoxy
thiophen
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DK13868493.1T
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Noriaki Iwase
Hiroshi Nishida
Makoto Okudo
Masaaki Ito
Shigeyuki Kono
Masaaki Matoyama
Shigeru Ushiyama
Eiji Okanari
Hirofumi Matsunaga
Kenji Nishikawa
Tomio Kimura
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Ube Industries
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

Claims (28)

1. Forbindelse repræsenteret af den generelle formel (I): [kemisk formel 320]
(I) hvor A repræsenterer, en phenyl-ring, en thiophen-ring, eller en isothiazol-ring; R1 er den samme eller forskellig, og repræsenterer et halogenatom, eller en Ci-C3-alkylgruppe; R2 repræsenterer et hydrogenatom, eller en Ci-C6-alkylgruppe; p repræsenterer et heltal fra 0 til 5; V repræsenterer CR3 hvor R3 repræsenterer et hydrogenatom, en aminogruppe, en nitrogruppe, eller en Ci-C3-alkoxygruppe, eller V repræsenterer et nitrogenatom; X repræsenterer et halogenatom, eller et farmakologisk acceptabelt salt deraf.
2. Forbindelsen ifølge krav 1, hvilken er repræsenteret af den generelle formel (la): [kemisk formel 321]
(la) hvor R1 er den samme eller forskellig, og repræsenterer et halogenatom, eller en Ci-C3-alkylgruppe, R2 repræsenterer et hydrogenatom, eller en C1-C6 -alkylgruppe; p repræsenterer et heltal fra 0 til 5; V repræsenterer CH eller et nitrogenatom; X repræsenterer et halogenatom, eller et farmakologisk acceptabelt salt deraf.
3. Forbindelsen ifølge krav 2 hvor, i den generelle formel (la), gruppen: [kemisk formel 322]
er valgt fra en gruppe bestående af grupperne: [kemisk formel 323]
eller et farmakologisk acceptabelt salt deraf.
4. Forbindelsen ifølge krav 2 hvor, i den generelle formel (la), gruppen: [kemisk formel 324]
er valgt fra en gruppe bestående af grupperne: [kemisk formel 325]
eller et farmakologisk acceptabelt salt deraf.
5. Forbindelsen ifølge krav 2, hvilken er valgt fra en gruppe bestående af: (RS)-l-{4'-[5-brom-3-({[l-(2- chlorphenyl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(2- chlorphenyl)ethoxy]carbonyl>amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2-chlorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-[4'-(5-chlor-3-{[(l-phenylethoxy)carbonyl]amino>thiophen-2-yl)- [l,l'-biphenyl]-4-yl]cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2-fluorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-[l,l,_biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(3-fluorphenyl)ethoxy]carbonyl>amino)thiophen- 2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(4-fluorphenyl)ethoxy]carbonyl>amino)thiophen- 2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(4-chlorphenyl)ethoxy]carbonyl>amino)thiophen- 2-yl]-[l,l,_biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(o-tolyl)ethoxy]carbonyl>amino)thiophen-2-yl]- [l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2,4- difluorphenyl)ethoxy]carbonyl>amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2,5- difluorphenyl)ethoxy]carbonyl>amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(3,4- difluorphenyl)ethoxy]carbonyl>amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2-chlor-4-fluorphenyl)ethoxy]carbonyl}amino)- thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-(5-chlor-3-{[(l-phenylethoxy)carbonyl]amino}thiophen-2-yl)- pyridin-2-yl]phenyl>cyclopropancarboxylsyre, (R)-l-[4'-(5-fluor-3-{[(l-phenylethoxy)carbonyl]amino}thiophen-2-yl)- [l,l'-biphenyl]-4-yl]cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(2-fluorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-[l,l,_biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(4-fluorphenyl)ethoxy]carbonyl>amino)thiophen- 2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(2-chlorphenyl)ethoxy]carbonyl>amino)-5-fluorthiophen- 2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(4-chlorphenyl)ethoxy]carbonyl>annino)-5-fluorthiophen- 2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(o-tolyl)ethoxy]carbonyl>amino)thiophen-2-yl]- [l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[3-({[ 1-(3,4-difluorphenyl)ethoxy]carbonyl}amino)-5-fluorthiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(2,4-difluorphenyl)ethoxy]carbonyl}amino)-5- fluorthiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(2-chlor-4-fluorphenyl)ethoxy]carbonyl}amino)-5- fluorthiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (RS)-l-{4'-[3-({[l-(4-chlor-2-fluorphenyl)ethoxy]carbonyl}amino)-5-fluorthiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, og (RS)-l-{4'-[5-fluor-3-({ [1-(2,4,5-trifluorphenyl)ethoxy]carbonyl>amino)-thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
6. Forbindelsen ifølge krav 1, hvor, i den generelle formel (I), V repræsenterer CR3 i hvilken R3 repræsenterer et hydrogenatom, en aminogruppe, en nitrogruppe, eller en C1-C3 -alkoxygruppe, eller V repræsenterer et nitrogenatom med det forbehold, at i et tilfælde hvor A repræsenterer en phenyl-ring, de er V ikke CH eller et nitrogenatom, eller et farmakologisk acceptabelt salt deraf.
7. Forbindelsen ifølge krav 6, hvilken er repræsenteret af den generelle formel (Ib): [kemisk formel 326]
(Ib) hvor R1 er den samme eller forskellig, og repræsenterer et halogenatom, eller en Ci-C3-alkylgruppe; R2 repræsenterer et hydrogenatom eller en C1-C6 -alkylgruppe; p repræsenterer et heltal fra 0 til 5; X repræsenterer et halogenatom, eller et farmakologisk acceptabelt salt deraf.
8. Forbindelsen ifølge krav 7 hvor, i den generelle formel (Ib), gruppen: [kemisk formel 327]
er valgt fra en gruppe bestående af grupperne: [kemisk formel 328]
eller et farmakologisk acceptabelt salt deraf.
9. Forbindelsen ifølge krav 7 hvor, i den generelle formel (Ib), gruppen: [kemisk formel 329]
er valgt fra en gruppe bestående af grupperne: [kemisk formel 330]
eller et farmakologisk acceptabelt salt deraf.
10. Forbindelsen ifølge krav 7, hvilken er valgt fra en gruppe bestående af: (R)-l-[4'-(5-chlor-3-{[(l-phenylethoxy)carbonyl]amino}thiophen-2-yl)-2'- methoxy-[l,l'-biphenyl]-4-yl]cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2-fluorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(3-fluorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(4-fluorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2-chlorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(4-chlorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(o-tolyl)ethoxy]carbonyl}amino)thiophen-2-yl]- 2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(3,4- difluorphenyl)ethoxy]carbonyl>amino)thiophen-2-yl]-2'-methoxy-[l,l'- biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2,5- difluorphenyl)ethoxy]carbonyl}amino)thiophen-2-yl]-2'-methoxy-[l,l'- biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2,4- difluorphenyl)ethoxy]carbonyl}amino)thiophen-2-yl]-2'-methoxy-[l,l'- biphenyl]-4-yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(2-chlor-5-fluorphenyl)ethoxy]carbonyl}- amino)thiophen-2-yl]-2'-methoxy-[l,r-biphenyl]-4- yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(2-chlor-4-fluorphenyl)ethoxy]carbonyl>amino)- thiophen-2-yl]-2'-methoxy-[l,l,-biphenyl]-4-yl>cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(5-fluor-2-methylphenyl)ethoxy]carbonyl>- amino)thiophen-2-yl]-2,-methoxy-[l,l,_biphenyl]-4- yl>cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(4-fluor-2-methylphenyl)ethoxy]carbonyl>- amino)thiophen-2-yl]-2,-methoxy-[l,l,_biphenyl]-4- yl>cyclopropancarboxylsyre, (R)-l-[4'-(5-fluor-3-{[(l-phenylethoxy)carbonyl]amino>thiophen-2-yl)-2'- methoxy-[l,l'-biphenyl]-4-yl]cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(2-fluorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(3-fluorphenyl)ethoxy]carbonyl}amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(4-fluorphenyl)ethoxy]carbonyl>amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(2-chlorphenyl)ethoxy]carbonyl}amino)-5-fluorthiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(4-chlorphenyl)ethoxy]carbonyl}amino)-5-fluorthiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(o-tolyl)ethoxy]carbonyl}amino)thiophen-2-yl]- 2'-methoxy-[l,r-biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(3,4-difluorphenyl)ethoxy]carbonyl}amino)-5- fluorthiophen-2-yl]-2'-methoxy-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(2,5-difluorphenyl)ethoxy]carbonyl}amino)-5- fluorthiophen-2-yl]-2'-methoxy-[l,r-biphenyl]-4- yl>cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(2,4-difluorphenyl)ethoxy]carbonyl}amino)-5- fluorthiophen-2-yl]-2'-methoxy-[l,l'-biphenyl]-4- yl>cyclopropancarboxylsyre, (RS)-l-{4'-[3-({[l-(2-chlor-5-fluorphenyl)ethoxy]carbonyl>amino)-5- fluorthiophen-2-yl]-2'-methoxy-[l,l,_biphenyl]-4- yl}cyclopropancarboxylsyre, (R)-l-{4'-[3-({[l-(2-chlor-4-fluorphenyl)ethoxy]carbonyl>amino)-5- fluorthiophen-2-yl]-2,-methoxy-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-fluor-3-({[l-(5-fluor-2-methylphenyl)ethoxy]carbonyl>-amino)thiophen-2-yl]-2,-methoxy-[l,l,_biphenyl]-4-yl>cyclopropancarboxylsyre, og (RS)-l-{4'-[5-fluor-3-({[l-(4-fluor-2-methylphenyl)ethoxy]carbonyl>- amino)thiophen-2-yl]-2,-methoxy-[l,l,_biphenyl]-4- yl>cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
11. Forbindelsen ifølge krav 6, hvor, i den generelle formel (I), V repræsenterer CR3 i hvilken R3 repræsenterer et hydrogenatom eller en methoxygruppe, eller V repræsenterer et nitrogenatom; og gruppen: [kemisk formel 331]
er valgt fra en gruppe bestående af grupperne: [kemisk formel 332]
eller et farmakologisk acceptabelt salt deraf.
12. Forbindelsen ifølge krav 6 hvor, i den generelle formel (I), gruppen: [kemisk formel 333]
er valgt fra en gruppe bestående af grupperne: [kemisk formel 334]
eller et farmakologisk acceptabelt salt deraf.
13. Forbindelsen ifølge krav 11, hvilken er valgt fra en gruppe bestående af: (RS)-l-{4'-[5-chlor-3-({[l-(thiophen-3- yl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,r-biphenyl]-4- yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(thiophen-3-yl)ethoxy]carbonyl>amino)thiophen- 2-yl]-[l,l,_biphenyl]-4-yl>cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(thiophen-3- yl)ethoxy]carbonyl>amino)thiophen-2-yl]-2'-methoxy-[l,l'-biphenyl]-4- yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(thiophen-3-yl)ethoxy]carbonyl>amino)thiophen- 2-yl]-2'-methoxy-[l,l,-biphenyl]-4-yl>cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(4-methylthiophen-3- yl)ethoxy]carbonyl>amino)-thiophen-2-yl]-[l,l'-biphenyl]-4- yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(4-methylthiophen-3- yl)ethoxy]carbonyl>amino)-thiophen-2-yl]-[l,l'-biphenyl]-4- yl>cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(4-methylthiophen-3- yl)ethoxy]carbonyl>amino)-thiophen-2-yl]-2,-methoxy-[l,l,_biphenyl]-4- yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(4-chlorthiophen-3-yl)ethoxy]carbonyl}amino)- thiophen-2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[(l-(isothiazol-3- yl)ethoxy]carbonyl>amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-chlor-3-({[l-(isothiazol-4- yl)ethoxy]carbonyl>amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (RS)-l-(4-{5-[5-chlor-3-({[l-(thiophen-3- yl)ethoxy]carbonyl}amino)thiophen-2-yl]pyridin-2- yl>phenyl)cyclopropancarboxylsyre, (RS)-l-(4-{5-[5-chlor-3-({[l-(4-methylthiophen-3-yl)ethoxy]carbonyl}- amino)thiophen-2-yl]pyridin-2-yl>phenyl)cyclopropancarboxylsyre, (RS)-l-{4'-[5-fluor-3-({[l-(thiophen-3- yl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,l'-biphenyl]-4- yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(thiophen-3-yl)ethoxy]carbonyl>amino)thiophen- 2-yl]-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-fluor-3-({[l-(thiophen-3- yl)ethoxy]carbonyl>amino)thiophen-2-yl]-2'-methoxy-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-fluor-3-({[l-(4-methylthiophen-3- yl)ethoxy]carbonyl}amino)-thiophen-2-yl]-[l,r-biphenyl]-4- yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(4-methylthiophen-3-yl)ethoxy]carbonyl>amino)- thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, (RS)-l-{4'-[5-fluor-3-({[l-(2-methylthiophen-3- yl)ethoxy]carbonyl>amino)-thiophen-2-yl]-[l,l'-biphenyl]-4- yl}cyclopropancarboxylsyre, (RS)-l-{4'-[5-fluor-3-({[l-(4-methylthiophen-3- yl)ethoxy]carbonyl}amino)-thiophen-2-yl]-2'-methoxy-[l,l,_biphenyl]-4- yl>cyclopropancarboxylsyre, (RS)-l-{4'-[3-({[l-(4-chlorthiophen-3-yl)ethoxy]carbonyl>amino)-5-fluor- thiophen-2-yl]-[l,r-biphenyl]-4-yl}cyclopropancarboxylsyre, (RS)-l-{4'-[3-({[l-(4-chlorthiophen-3-yl)ethoxy]carbonyl>amino)-5-fluor- thiophen-2-yl]-2'-methoxy-[l,l,-biphenyl]-4-yl>cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(thiophen-2-yl)ethoxy]carbonyl>amino)thiophen- 2-yl]-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-chlor-3-({[l-(thiophen-2-yl)ethoxy]carbonyl>amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, (R)-l-{4'-[5-fluor-3-({[l-(thiophen-2-yl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, og (R)-l-{4'-[5-fluor-3-({[l-(thiophen-2-yl)ethoxy]carbonyl>amino)thiophen- 2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
14. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-chlor-3-({[l-(2-chlorphenyl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
15. Forbindelsen ifølge krav i, hvilken er: (R)-l-{4'-[5-chlor-3-({[l-(3-fluorphenyl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
16. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[3-({[l-(2-chlorphenyl)ethoxy]carbonyl}amino)-5-fluorthiophen-2-yl]-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
17. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-fluor-3-({[l-(o-tolyl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
18. Forbindelsen ifølge krav 1, hvilken er: (R)-l-[4,-(5-chlor-3-{[(l-phenylethoxy)carbonyl]amino>thiophen-2-yl)-2'-methoxy-[l,l,_biphenyl]-4-yl]cyclopropancarboxylsyre, eller et farmakologisk acceptabelt salt deraf.
19. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-chlor-3-({[l-(2,5-difluorphenyl)ethoxy]carbonyl>-amino)thiophen-2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl}cyclopropancarboxylsyre, eller farmakologisk acceptabelt salt deraf.
20. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[3-({[l-(2-chlorphenyl)ethoxy]carbonyl}amino)-5-fluorthio-phen-2-yl]-2'-methoxy-[l,r-biphenyl]-4-yl}cyclopropancarboxylsyre, eller farmakologisk acceptabelt salt deraf.
21. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-chlor-3-({[l-(thiophen-3-yl)ethoxy]carbonyl}amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller farmakologisk acceptabelt salt deraf.
22. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-chlor-3-([l-(thiophen-3-yl)ethoxy]carbonyl}amino)thiophen-2-yl]-2'-methoxy-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller farmakologisk acceptabelt salt deraf.
23. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-chlor-3-([l-(4-methylthiophen-3-yl)ethoxy]carbonyl>-amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller farmakologisk acceptabelt salt deraf.
24. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-fluor-3-({[l-(thiophen-3-yl)ethoxy]carbonyl>amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller farmakologisk acceptabelt salt deraf.
25. Forbindelsen ifølge krav 1, hvilken er: (R)-l-{4'-[5-fluor-3-({[l-(4-methylthiophen-3-yl)ethoxy]carbonyl>-amino)thiophen-2-yl]-[l,l'-biphenyl]-4-yl>cyclopropancarboxylsyre, eller farmakologisk acceptabelt salt deraf.
26. LPA-receptor-antagonist omfattende forbindelsen eller et farmakologisk acceptabelt salt deraf ifølge et hvilket som helst af kravene 1 til 25 som en aktiv ingrediens.
27. Farmaceutisk sammensætning omfattende forbindelsen eller et farmakologisk acceptabelt salt deraf ifølge et hvilket som helst af kravene 1 til 25 som en aktiv ingrediens.
28. Den farmaceutiske sammensætning ifølge krav 27 til anvendelse i behandlingen eller forebyggelsen af en sygdom ledsagende fibrose, en immunologisk eller inflammatorisk sygdom, en sygdom i det centrale eller perifere nervesystem, en urologisk sygdom eller en kræft-relateret sygdom.
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