HRP20171200T1 - Novi derivati benzimidazola kao antagonisti ep4 - Google Patents

Novi derivati benzimidazola kao antagonisti ep4 Download PDF

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HRP20171200T1
HRP20171200T1 HRP20171200TT HRP20171200T HRP20171200T1 HR P20171200 T1 HRP20171200 T1 HR P20171200T1 HR P20171200T T HRP20171200T T HR P20171200TT HR P20171200 T HRP20171200 T HR P20171200T HR P20171200 T1 HRP20171200 T1 HR P20171200T1
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ethyl
carbazol
carboxylic acid
benzimidazole
alkyl
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Olaf Peters
Nico BRÄUER
Thorsten Blume
Antonius Ter Laak
Ludwig Zorn
Jens Nagel
Stefan KAULFUSS
Gernot Langer
Joachim Kuhnke
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Bayer Pharma Aktiengesellschaft
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    • C—CHEMISTRY; METALLURGY
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
    • 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
    • A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • 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
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
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    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings

Claims (13)

1. Spojevi opće formule (I)  [image] naznačeni time da R1a, R1b neovisno jedan od drugoga predstavljaju H, C1-C5-alkil, C2-C5-alkenil, C2-C5-alkinil, C3-C6-cikloalkil-(CH2)m, C3-C6-heterocikloalkil-(CH2)n, C1-C5-alkoksi-C1-C3-alkil, C3-C6-cikloalkoksi-C1-C3-alkil, amino-C1-C3-alkil, C1-C5-alkilamino-C1-C3-alkil, C1-C5-dialkilamino-C1-C3-alkil ili cijano, gdje je proizvoljno prisutna heterociklička jedinica poželjno odabrana iz skupine koju čine oksetan, tetrahidrofuran, tetrahidropiran, 1,4-dioksan, morfolin, azetidin, pirolidin, piperazin i piperidin i gdje proizvoljno prisutni radikali alkil, cikloalkil ili heterocikloalkil mogu biti mono- ili polisupstituirani, identično ili različito s halogenom, C1-C5-alkil, hidroksil, karboksil, karboksi-C1-C5-alkil, C1-C5-alkoksikarbonil-C1-C5-alkil ili C1-C5-alkilsulfonil, R4 predstavlja H, F, Cl, C1-C2-alkil, C3-C5-cikloalkil, C1-C2-alkoksi ili C3-C4-cikloalkilmetil, gdje odgovarajuća alkil ili cikloalkil jedinica može biti mono- ili polisupstituirana, istovjetno ili različito s halogenom ili hidroksilom, A predstavlja RO-CO(CH2)p, gdje R predstavlja H ili C1-C2-alkil, m je 0, 1, 2 ili 3, n je 0, 1, 2 ili 3, p je 0, i B je odabran od slijedećih struktura, [image] [image] R6 , predstavlja H, F, Cl, CH3, CF3 CH3O ili CF3O, R7, R8 svaki puta neovisno jedan od drugoga predstavljaju H, F, Cl, cijano, SF5, C1-C3-alkil, C3-C5-cikloalkil, C1-C2-alkoksi ili C3-C4-cikloalkilmetil, gdje odgovarajuća alkil ili cikloalkil jedinica može biti mono- ili polihalogenirana, i R9 predstavlja C1-C5-alkil, C2-C5-alkenil, C2-C5-alkinil, C3-C6-cikloalkil-(CH2)n, C3-C6-heterocikloalkil-(CH2)n, ili C1-C7-alkoksi-C2-C5-alkil, gdje je proizvoljno prisutna heterociklička jedinica odabrana iz skupine koju čine oksetan, tetrahidrofuran, tetrahidropiran, morfolin, pirolidin i piperidin i gdje proizvoljno prisutne jedinice alkil, cikloalkil ili heterocikloalkil mogu biti mono- ili polisupstituirane, istovjetno ili različito s halogenom, C1-C2-alkilom, C1-C2-alkoksi ili karboksilom, i njihovi izomeri, dijastereomeri, enantiomeri, solvati i soli ili klatrati ciklodekstrina.
2. Spojevi prema zahtjevu 1, naznačeni time da R1a predstavlja H ili C1-C5-alkil, R1b predstavlja H, C1-C5-alkil, C2-C5-alkenil, C3-C6-cikloalkil-(CH2)m, C3-C6-heterocikloalkil-(CH2)n, C1-C5-alkoksi-C1-C3-alkil ili C1-C5-dialkilamino-C1-C3-alkil, gdje proizvoljno prisutna heterociklička jedinica je poželjno odabrana iz skupine koju čine oksetan, tetrahidrofuran, 1,4-dioksan, morfolin i pirolidin i gdje proizvoljno prisutni radikali alkil- ili cikloalkil mogu biti mono- ili polisupstituirani, istovjetno ili različito, s C1-C5-alkilom, hidroksilom, ili C1-C5-alkilsulfonilom, R4 predstavlja H, F, Cl, C1-C2-alkil ili C1-C2-alkoksi, A predstavlja RO-CO(CH2)p, gdje R predstavlja H ili C1-C2-alkil, m je 0 ili 1, n je 0 ili 1, p je 0, i B je odabran od slijedećih struktura, [image] [image] R6 predstavlja H, F, CH3 ili CH3O, R7, R8 svaki puta neovisno jedan od drugoga predstavljaju H, F, Cl, C1-C3-alkil ili C1-C2-alkoksi, i R9 predstavlja C1-C5-alkil, C2-C5-alkenil, C2-C5-alkinil, C3-C6-cikloalkil-(CH2)n ili C1-C7-alkoksi-C2-C5-alkil, i njihovi izomeri, dijastereomeri, enantiomeri, solvati i soli ili klatrati ciklodekstrina.
3. Spojevi prema zahtjevu 1, naznačeni time da R1a predstavlja H ili metil, R1b predstavlja H, C1-C2-alkil, vinil, ciklopropil-(CH2)m, C3-C6-heterocikloalkil-(CH2)n, metoksi-C1-C2-alkil ili (N,N-dimetilamino)-metil, gdje je proizvoljno prisutna heterociklička jedinica poželjno odabrana iz skupine koju čine oksetan, tetrahidrofuran, 1,4-dioksan, morfolin i pirolidin i gdje proizvoljno prisutni radikali alkil ili cikloalkil mogu biti mono- ili polisupstituirani, istovjetno ili različito, s metilom, hidroksilom, ili metilsulfonilom, R4 predstavlja H, F, Cl, metil ili metoksi, A predstavlja RO-CO(CH2)p, gdje R predstavlja H ili C1-C2-alkil, m je 0 ili 1, n je 0 ili 1, p je 0, i B je odabran od slijedećih struktura, [image] [image] R6 predstavlja H, F, CH3 ili CH3O, R7, R8 svaki puta neovisno jedan od drugoga predstavljaju H, F, Cl, metil ili metoksi, i R9 predstavlja C1-C3-alkil, alil, propargil, C3-C4-cikloalkil-(CH2)n ili metoksietil, i njihovi izomeri, dijastereomeri, enantiomeri, solvati i soli ili klatrati ciklodekstrina.
4. Spojevi prema zahtjevu 1, naznačeni time da R1a predstavlja H ili metil, R1b predstavlja H, C1-C2-alkil, vinil, ciklopropil-(CH2)m, C3-C6-heterocikloalkil-(CH2)n, metoksi-C1-C2-alkil ili (N,N-dimetilamino)-metil, gdje je proizvoljno prisutna heterociklička jedinica poželjno odabrana iz skupine koju čine oksetan, tetrahidrofuran, 1,4-dioksan, morfolin i pirolidin i gdje proizvoljno prisutni radikali alkil ili cikloalkil mogu biti mono- ili polisupstituirani, istovjetno ili različito, s metilom, hidroksilom, ili metilsulfonilom, R4 predstavlja H, F, Cl, metil ili metoksi, A predstavlja RO-CO(CH2)p, gdje R predstavlja H, m je 0 ili 1, n je 0 ili 1, p je 0, i B je odabran od slijedećih struktura, [image] [image] R6 predstavlja H, F, CH3 ili CH3O, R7, R8 svaki puta neovisno jedan od drugoga predstavljaju H, F, Cl, metil ili metoksi, i R9 predstavlja C1-C3-alkil, alil, propargil, C3-C4-cikloalkil-(CH2)n ili metoksietil, i njihovi izomeri, dijastereomeri, enantiomeri, solvati i soli ili klatrati ciklodekstrina.
5. Spojevi prema zahtjevu 1, naznačeni time da R1a predstavlja H, R1b predstavlja metoksimetil, R4 predstavlja H, F, Cl, metil ili metoksi, A predstavlja RO-CO(CH2)p, gdje R predstavlja H, n je 0 ili 1, p je 0, i B je odabran od slijedećih struktura, [image] R6 , predstavlja H, F, CH3 ili CH3O, R7, R8 svaki puta neovisno jedan od drugoga predstavljaju H, F, Cl, metil ili metoksi, i R9 predstavlja C1-C3-alkil, alil, propargil, C3-C4-cikloalkil-(CH2)n ili metoksietil, i njihovi izomeri, dijastereomeri, enantiomeri, solvati i soli ili klatrati ciklodekstrina.
6. Spoj prema zahtjevu 1 naznačen time da je odabran iz skupine koja sadrži slijedeće spojeve: 1. metil 1-alil-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilat 2. 1-alil-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 3. metil 2-(9-etil-9H-karbazol-3-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilat 4.2-(9-etil-9H-karbazol-3-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 5. metil 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilat 6. 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 7. metil 4-chloro-1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimid-azole-5-karboksilat 8. 4-kloro-1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 9. 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-4-metil-1H-benzimidazol-5-karboksilna kiselina 10. 2-(9-etil-7-fluoro-9H-karbazol-3-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 11. 2-(9-etil-5-fluoro-9H-karbazol-3-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 12. 2-(9-etil-8-fluoro-9H-karbazol-3-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 13. 1-(ciklopropilmetil)-2-[9-(2-metoksietil)-9H-karbazol-3-il]-1H-benzimidazol-5-karboksilna kiselina 14. 1-(ciklopropilmetil)-2-(9-etil-9H-pirido[2,3-b]indol-3-il)-1H-benzimidazol-5-karboksilna kiselina 15. 2-(9-etil-6-metoksi-9H-karbazol-3-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 16. 2-(9-alil-9H-karbazol-3-il)-1-(ciklopropilmetil)-1H-benzimidazol-5-karboksilna kiselina 17. 1-(ciklopropilmetil)-2-(9-metil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 18. 1-(ciklopropilmetil)-2-[9-(ciklopropilmetil)-9H-karbazol-3-il]-1H-benzimidazol-5-karboksilna kiselina 19. 2-[9-(ciklopropilmetil)-9H-karbazol-3-il]-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 20. etil-2-(9-etil-9H-karbazol-3-il)-1-[2-(pirolidin-1-il)etil]-1H-benzimidazol-5-karboksilat 21. 2-(9-etil-9H-karbazol-3-il)-1-[2-(pirolidin-1-il)etil]-1H-benzimidazol-5-karboksilna kiselina 22. 2-(5-etil-5H-pirido[3,2-b]indol-2-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 23. 1-(ciklopropilmetil)-2-(9-etil-6-metoksi-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 24. 2-(9-etil-9H-karbazol-3-il)-1-[2-(morfolin-4-il)etil]-1H-benzimidazol-5-karboksilna kiselina 25. etil-1-[2-(dimetilamino)etil]-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilat 26. 1-[2-(dimetilamino)etil]-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 27. 2-(9-etil-9H-karbazol-3-il)-1-(2-hidroksietil)-1H-benzimidazol-5-karboksilna kiselina 28. etil-2-(9-etil-9H-karbazol-3-il)-1-izopropil-1H-benzimidazol-5-karboksilat 29. 2-(9-etil-9H-karbazol-3-il)-1-izopropil-1H-benzimidazol-5-karboksilna kiselina 30. 2-(9-etil-9H-karbazol-3-il)-1-metil-1H-benzimidazol-5-karboksilna kiselina 31. metil 1-etil-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilat 32. 2-(9-alil-9H-karbazol-3-il)-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 33. etil 1-(2-metoksietil)-2-[9-(2-metoksietil)-9H-karbazol-3-il]-1H-benzimidazol-5-karboksilat 34. 1-(2-metoksietil)-2-[9-(2-metoksietil)-9H-karbazol-3-il]-1H-benzimidazol-5-karboksilna kiselina 35. etil 2-(9-etil-9H-karbazol-3-il)-1-(3-metoksipropil)-1H-benzimidazol-5-karboksilat 36. 2-(9-etil-9H-karbazol-3-il)-1-(3-metoksipropil)-1H-benzimidazol-5-karboksilna kiselina 37. 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-6-metoksi-1H-benzimidazol-5-karboksilna kiselina 38. 2-(9-etil-9H-karbazol-3-il)-6-metoksi-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 39. 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-4-metoksi-1H-benzimidazol-5-karboksilna kiselina 40. 2-(9-etil-9H-karbazol-3-il)-1-(2-metoksietil)-4-metil-1H-benzimidazol-5-karboksilna kiselina 41. 1-(ciklopropilmetil)-2-(9-etil-9H-pirido[2,3-b]indol-3-il)-4-metil-1H-benzimidazol-5-karboksilna kiselina 42. 1-(ciklopropilmetil)-2-(9-etil-9H-beta-karbolin-6-il)-1H-benzimidazol-5-karboksilna kiselina 43. 1-(ciklopropilmetil)-2-(5-etil-5H-pirido[4,3-b]indol-8-il)-1H-benzimidazol-5-karboksilna kiselina 44. 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-6-metil-1H-benzimidazol-5-karboksilna kiselina 45. 2-(9-etil-9H-karbazol-3-il)-1-(2-metoksietil)-6-metil-1H-benzimidazol-5-karboksilna kiselina 46. 2-(9-etil-9H-karbazol-3-il)-6-fluoro-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 47. 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-6-fluoro-1H-benzimidazol-5-karboksilna kiselina 48. 2-(9-etil-9H-karbazol-3-il)-4-fluoro-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 49. 1-(ciklopropilmetil)-2-(9-etil-9H-karbazol-3-il)-4-fluoro-1H-benzimidazol-5-karboksilna kiselina 50. 1-(ciklopropilmetil)-2-(9-etil-9H-pirido[2,3-b]indol-6-il)-1H-benzimidazol-5-karboksilna kiselina 51. 1-(2-ciklopropiletil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 52. 1-(2-metoksietil)-2-(9-propil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 53. 1-(2-metoksietil)-2-[9-(prop-2-in-1-il)-9H-karbazol-3-il]-1H-benzimidazol-5-karboksilna kiselina 54. 1-(ciklopropilmetil)-2-(9-propil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 55. 1-[(2,2-Dimetilciklopropil)metil]-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 56. etil 2-(9-etil-9H-karbazol-3-il)-1-(oksetan-3-ilmetil)-1H-benzimidazol-5-karboksilat 57. 2-(9-etil-9H-karbazol-3-il)-1-(oksetan-3-ilmetil)-1H-benzimidazol-5-karboksilna kiselina 58. 2-[9-(ciklobutilmetil)-9H-karbazol-3-il]-1-(2-metoksietil)-1H-benzimidazol-5-karboksilna kiselina 59. 2-[9-(ciklobutilmetil)-9H-karbazol-3-il]-1-(ciklopropilmetil)-1H-benzimidazol-5-karboksilna kiselina 60. 2-(9-etil-9H-karbazol-3-il)-1-[2-(trifluorometoksi)etil]-1H-benzimidazol-5-karboksilna kiselina 61. 1-(ciklopropilmetil)-2-(9-etil-1-metil-9H-beta-karbolin-3-il)-1H-benzimidazol-5-karboksilna kiselina 62. 2-(9-etil-9H-karbazol-3-il)-1-(oksetan-2-ilmetil)-1H-benzimidazol-5-karboksilna kiselina 63. 2-(9-etil-9H-karbazol-3-il)-1-(tetrahidrofuran-2-ilmetil)-1H-benzimidazol-5-karboksilna kiselina 64. 2-(9-etil-9H-karbazol-3-il)-1-[(2R)-2-hidroksi-3-metoksipropil]-1H-benzimidazol-5-karboksilna kiselina 65. 2-(9-etil-9H-karbazol-3-il)-1-[(2S)-2-hidroksi-3-metoksipropil]-1H-benzimidazol-5-karboksilna kiselina 66. 2-(9-etil-9H-karbazol-3-il)-1-[2-(metilsulfonil)etil]-1H-benzimidazol-5-karboksilna kiselina 67. 1-(2-ciklopropil-2-hidroksietil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 68. 1-[(2S)-2,3-dihidroksipropil]-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 69. 1-(1,4-dioksan-2-ilmetil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 70. 1-(1,4-dioksan-2-ilmetil)-2-(9-etil-9H-karbazol-3-il)-1H-benzimidazol-5-karboksilna kiselina 71. 2-(9-etil-6-metil-9H-karbazol-3-il)-1-(2-metoksietil)-4-metil-1H-benzimidazol-5-karboksilna kiselina 72. 2-(6-kloro-9-etil-9H-karbazol-3-il)-1-(2-metoksietil)-4-metil-1H-benzimidazol-5-karboksilna kiselina 73. 2-(8-kloro-9-etil-9H-karbazol-3-il)-1-(2-metoksietil)-4-metil-1H-benzimidazol-5-karboksilna kiselina
7. Spoj s formulom (I), kako je definirano u jednom od zahtjeva 1 do 6, naznačen time da je za liječenje i/ili profilaksu bolesti.
8. Spoj s formulom (I), kako je definirano u jednom od zahtjeva 1 do 6, naznačen time da je za uporabu u postupku liječenja i/ili profilaksu endometrioze, leiomioma maternice, poremećaja krvarenja maternice, gdje poremećaji krvarenja mogu biti teško i dugotrajno krvarenje, privremeno nepravilno krvarenje i bol, dismenoreje, raka, gdje rak može biti rak pluća, crijeva, dojke, kože, rak prostate, jednjaka i leukemija, za liječenje arterioskleroze i policističnih bolesti bubrega.
9. Uporaba spoja prema zahtjevu 1, 2, 3, 4, 5 ili 6 naznačena time da je za proizvodnju lijeka za liječenje i/ili profilaksu bolesti.
10. Uporaba spoja, kako je definirano u jednom od zahtjeva 1 do 6, naznačena time da je za proizvodnju lijeka za liječenje i/ili profilaksu endometrioze, leiomioma maternice, poremećaja krvarenja maternice, gdje poremećaji krvarenja mogu biti teško i dugotrajno krvarenje, privremeno nepravilno krvarenje i bol, dismenoreje, raka, gdje rak može biti rak pluća, crijeva, dojke, kože, rak prostate, jednjaka i leukemija, za liječenje arterioskleroze i policističnih bolesti bubrega.
11. Lijek naznačen time da sadrži spoj, kako je definirano u jednom od zahtjeva 1 do 6, u kombinaciji s jednom ili više dodatnih aktivnih tvari, naročito sa selektivnim modulatorima estrogenskih receptora (SERM), antagonistima receptora estrogena (ER), inhibitorima aromataze, inhibitorima 17β-HSD1, inhibitorima steroidne sulfataze (STS), agonistima i antagonistima GnRH, antagonistima kisspeptin receptora (KISSR), selektivnim modulatorima androgenskih receptora (SARM), androgenima, inhibitorima 5α-reduktaze, selektivnima modulatorima receptora progesterona (SPRM), gestagenima, antigestagenima, oralnim kontracepcijskim sredstvima, inhibitorima mitogenom aktiviranih protein (MAP) kinaza i inhibitorima MAP kinaza (Mkk3/6, Mek1/2, Erk1/2), inhibitorima protein kinaza B (PKBα/β/γ; Akt1/2/3), inhibitorima fosfoinositid-3 kinaze (PI3K), inhibitorima kinaze ovisne o ciklinima (CDK1/2), inhibitorima puta inducibilnog signala hipoksije (HIF1alfa inhibitori, aktivatori prolilhidroksilaza), inhibitorima histonske deacetilaze (HDAC), antagonistima receptora prostaglandina F (FP) (PTGFR), antagonistima neurokinin 1 receptora, paracetamolom, selektivnim inhibitorima COX2 i/ili ne-selektivnim inhibitorima COX1/COX2.
12. Lijek naznačen time da sadrži spoj s formulom (I) kako je definirano u jednom od zahtjeva 1 do 6, u kombinaciji s inertnim, netoksičnim farmaceutskim pogodnim pomoćnim sredstvom.
13. Lijek prema zahtjevu 11 ili 12 naznačen time da je za liječenje i/ili profilaksu endometrioze, leiomioma maternice, poremećaja krvarenja maternice, gdje poremećaji krvarenja mogu biti teško i dugotrajno krvarenje, privremeno nepravilno krvarenje i bol, dismenoreje, raka, gdje rak može biti rak pluća, crijeva, dojke, kože, rak prostate, jednjaka i leukemija, za liječenje arterioskleroze i policističnih bolesti bubrega.
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