HRP20180029T1 - Derivati oktahidro-ciklobuta[1,2-c;3,4-c']dipirola kao inhibitori autotaksina - Google Patents
Derivati oktahidro-ciklobuta[1,2-c;3,4-c']dipirola kao inhibitori autotaksina Download PDFInfo
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- HRP20180029T1 HRP20180029T1 HRP20180029TT HRP20180029T HRP20180029T1 HR P20180029 T1 HRP20180029 T1 HR P20180029T1 HR P20180029T T HRP20180029T T HR P20180029TT HR P20180029 T HRP20180029 T HR P20180029T HR P20180029 T1 HRP20180029 T1 HR P20180029T1
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- Prior art keywords
- carbonyl
- octahydro
- cyclobuta
- substituted
- dipyrrol
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- ULUNQYODBKLBOE-UHFFFAOYSA-N 2-(1h-pyrrol-2-yl)-1h-pyrrole Chemical class C1=CNC(C=2NC=CC=2)=C1 ULUNQYODBKLBOE-UHFFFAOYSA-N 0.000 title 1
- 102100021977 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Human genes 0.000 title 1
- 108050004000 Ectonucleotide pyrophosphatase/phosphodiesterase family member 2 Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 17
- -1 9H-carbazolyl Chemical group 0.000 claims 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 12
- 125000004076 pyridyl group Chemical group 0.000 claims 9
- 229910052736 halogen Inorganic materials 0.000 claims 7
- 150000002367 halogens Chemical class 0.000 claims 7
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 5
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims 4
- 125000004607 1,2,3,4-tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims 4
- 125000003016 chromanyl group Chemical group O1C(CCC2=CC=CC=C12)* 0.000 claims 4
- 125000001041 indolyl group Chemical group 0.000 claims 4
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims 4
- 125000001624 naphthyl group Chemical group 0.000 claims 4
- 125000002971 oxazolyl group Chemical group 0.000 claims 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims 4
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims 4
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims 3
- 125000004122 cyclic group Chemical group 0.000 claims 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- KQGJFNOAZQYCQN-SEXKYXSUSA-N [4-(trifluoromethoxy)phenyl]methyl (1S,2R,6S,7R)-9-(2H-benzotriazole-5-carbonyl)-4,9-diazatricyclo[5.3.0.02,6]decane-4-carboxylate Chemical compound [H][C@]12CN(C[C@@]1([H])[C@]1([H])CN(C[C@]21[H])C(=O)C1=CC=C2NN=NC2=C1)C(=O)OCC1=CC=C(OC(F)(F)F)C=C1 KQGJFNOAZQYCQN-SEXKYXSUSA-N 0.000 claims 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 2
- 230000001684 chronic effect Effects 0.000 claims 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 2
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims 2
- 125000001544 thienyl group Chemical group 0.000 claims 2
- FFRQEGAWOFKEAT-AJCLOXLSSA-N (3,5-dichlorophenyl)methyl (1R,2S,6R,7S)-9-(2,3,3a,4,5,6,7,7a-octahydro-1H-benzotriazole-5-carbonyl)-4,9-diazatricyclo[5.3.0.02,6]decane-4-carboxylate Chemical compound C1CC2C(CC1C(=O)N3C[C@@H]4[C@H](C3)[C@@H]5[C@H]4CN(C5)C(=O)OCC6=CC(=CC(=C6)Cl)Cl)NNN2 FFRQEGAWOFKEAT-AJCLOXLSSA-N 0.000 claims 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 1
- NSHUGUYQKIEWIE-ZDNVTZCJSA-N 2H-benzotriazol-5-yl-[(1R,2S,6R,7S)-9-(6-chloronaphthalen-2-yl)sulfonyl-4,9-diazatricyclo[5.3.0.02,6]decan-4-yl]methanone Chemical compound [H][C@]12CN(C[C@@]1([H])[C@]1([H])CN(C[C@]21[H])S(=O)(=O)C1=CC=C2C=C(Cl)C=CC2=C1)C(=O)C1=CC=C2NN=NC2=C1 NSHUGUYQKIEWIE-ZDNVTZCJSA-N 0.000 claims 1
- DEZGHYZZFUJVJV-UJOPUZHASA-N 2H-benzotriazol-5-yl-[(1S,2R,6S,7R)-9-[6-(trifluoromethyl)-3,4-dihydro-1H-isoquinoline-2-carbonyl]-4,9-diazatricyclo[5.3.0.02,6]decan-4-yl]methanone Chemical compound [H][C@]12CN(C[C@@]1([H])[C@]1([H])CN(C[C@]21[H])C(=O)C1=CC=C2NN=NC2=C1)C(=O)N1CCC2=C(C1)C=CC(=C2)C(F)(F)F DEZGHYZZFUJVJV-UJOPUZHASA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 206010028980 Neoplasm Diseases 0.000 claims 1
- 208000003251 Pruritus Diseases 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 201000011510 cancer Diseases 0.000 claims 1
- 230000001587 cholestatic effect Effects 0.000 claims 1
- 208000030533 eye disease Diseases 0.000 claims 1
- 230000003176 fibrotic effect Effects 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 230000004968 inflammatory condition Effects 0.000 claims 1
- 210000003734 kidney Anatomy 0.000 claims 1
- 208000017169 kidney disease Diseases 0.000 claims 1
- 208000019423 liver disease Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 208000030159 metabolic disease Diseases 0.000 claims 1
- CKJNUZNMWOVDFN-UHFFFAOYSA-N methanone Chemical compound O=[CH-] CKJNUZNMWOVDFN-UHFFFAOYSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 claims 1
- 210000000653 nervous system Anatomy 0.000 claims 1
- 229910052757 nitrogen Inorganic materials 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 239000000825 pharmaceutical preparation Substances 0.000 claims 1
- 125000002071 phenylalkoxy group Chemical group 0.000 claims 1
- 238000011321 prophylaxis Methods 0.000 claims 1
- 210000002345 respiratory system Anatomy 0.000 claims 1
- 208000023504 respiratory system disease Diseases 0.000 claims 1
- 125000001424 substituent group Chemical group 0.000 claims 1
- 238000011282 treatment Methods 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 208000019553 vascular disease Diseases 0.000 claims 1
Classifications
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/407—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- 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
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
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- A61P13/00—Drugs for disorders of the urinary system
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
Claims (15)
1. Spojevi, naznačeni time, da imaju formulu (I)
[image]
u kojoj
R1 je supstituirani kinolinil, supstituirani 1,2,3,4-tetrahidrokinolinil, supstituirani izokinolinil, supstituirani 1,2,3,4-tetrahidroizokinolinil, supstituirani 9H-karbazolil, supstituirani kromanil, supstituirani indolil, supstituirani naftil, supstituirani oksazolil, supstituirani fenil, supstituirani fenil-C1-C7-alkil, supstituirani fenil-C3-C8-cikloalkil, supstituirani fenoksi-C1-C7-alkil, supstituirani fenil-C1-C7-alkoksi, supstituirani fenil-C2-C7-alkenil, supstituirani fenilalkinil, supstituirani piridazinil, supstituirani piridazinil-C1-C7-alkil, supstituirani piridazinil-C2-C7-alkinil, supstituirani piridazinlalkinil, supstituirani piridinil, supstituirani piridinil-C1-C7-alkil, supstituirani piridinil-C2-C7-alkenil, supstituirani piridinilalkinil, supstituirani piridinonil, supstituirani piridinonil-C1-C7-alkil, supstituirani piridinonil-C2-C7-alkinil, supstituirani piridinonilalkinil, supstituirani tiofenil, supstituirani tiofenil-C1-C7-alkil supstituirani tiofenil-C2-C7-alkenil, supstituirani tiofenilalkinil, supstituirani tetralinil ili supstituirani tetralinonil,
pri čemu su supstituirani kinolinil, supstituirani 1,2,3,4-tetrahidrokinolinil, supstituirani izokinolinil, supstituirani 1,2,3,4-tetrahidroizokinolinil, supstituirani 9H-karbazolil, supstituirani kromanil, supstituirani indolil, supstituirani naftil, supstituirani oksazolil, supstituirani fenil, supstituirani fenil-C1-C7-alkil, supstituirani fenil-C3-C8-cikloalkil, supstituirani fenoksi-C1-C7-alkil, supstituirani fenil-C1-C7-alkoksi, supstituirani fenil-C2-C7-alkenil, supstituirani fenilalkinil, supstituirani piridazinil, supstituirani piridazinil-C1-C7-alkil, supstituirani piridazinil-C2-C7-alkenil, supstituirani piridazinilalkinil, supstituirani piridinil, supstituirani piridinil-C1-C7-alkil, supstituirani piridinil-C2-C7-alkenil, supstituirani piridinilalkinil, supstituirani piridinonil, supstituirani piridinonil-C1-C7-alkil, supstituirani piridinonil-C2-C7-alkenil, supstituirani piridinonilalkinil, supstituirani tiofenil, supstituirani tiofenil-C1-C7-alkil, supstituirani tiofenil-C2-C7-alkenil, supstituirani tiofenilalkinil, supstituirani tetralinil i supstituirani tetralinonil zamijenjeni s R6, R7 i R8;
Y je -C(O)- ili-S(O)2-;
R2 je supstituirani piridinil, supstituirani fenil ili je odabran iz prstenastih sustava A, B i C, pri čemu su supstituirani piridinil i supstituirani fenil zamijenjeni s jednim supstituiranim aminosulfonilom, pri čemu je supstituirani aminosulfonil zamijenjen na dušikovom atomu s jednim do dva supstituenta neovisno odabrana između H, C1-C7-alkila, C3-C8-cikloalkila, C3-C8-cikloalkil-C1-C7-alkila, hidroksi-C1-C7-alkila i C1-C7-alkoksi-C1-C7-alkila;
[image]
R3, R4 i R5 su neovisno odabrani između H, C1-C7-alkila, halogena, halo-C1-C7-alkila i C1-C7-alkoksi;
R6, R7 i R8 su neovisno odabrani iz skupine koju čine H, halogen, cijano, cijano-C1-C7-alkil, C1-C7-alkil, hidroksi-C1-C7-alkil, haloalkil, hidroksihalo-C1-C7-alkil, C3-C8-cikloalkil, C3-C8-cikloalkil-C1-C7-alkil, C3-C8-cikloalkil-C1-C7-alkoksi, C3-C8-cikloalkoksi, C3-C8-cikloalkoksi-C1-C7-alkil, C3-C8-cikloalkil-C1-C7-alkoksi-C1-C7-alkil, C1-C7-alkoksi, C1-C7-alkoksi-C1-C7-alkil, halo-C1-C7-alkoksi, C1-C7-alkoksihalo-C1-C7-alkil, C1-C7-alkoksi-C1-C7-alkoksi, C1-C7-alkoksi-C1-C7-alkoksi-C1-C7-alkil, C1-C7-alkilsulfonil, furanil, tetrahidropiranil, fenil, supstituirani fenil, fenil-C1-C7-alkoksi, supstituirani fenil-C1-C7-alkoksi, piridinil, supstituirani piridinil, pirolil, supstituirani pirolil, pirolidinil i supstituirani pirolidinil, pri čemu su supstituirani fenil, supstituirani fenilalkoksi, supstituirani piridinil, supstituirani pirolil i supstituirani pirolidinil zamijenjeni s jednim do tri halogena;
ili farmaceutski prihvatljive soli.
2. Spoj prema zahtjevu 1, naznačen time, da R1 je supstituirani kinolinil, supstituirani 1,2,3,4-tetrahidrokinolinil, supstituirani izokinolinil, supstituirani 1,2,3,4-tetrahidroizokinolinil, supstituirani 9H-karbazolil, supstituirani kromanil, supstituirani indolil, supstituirani naftil, supstituirani oksazolil, supstituirani fenil, supstituirani fenil-C1-C7-alkil, supstituirani fenoksi-C1-C7-alkil, supstituirani fenil-C1-C7-alkoksi, supstituirani fenil-C2-C7-alkenil, supstituirani piridazinil, supstituirani piridinil, supstituirani piridinonil, supstituirani tetralinil ili supstituirani tetralinonil, pri čemu su supstituirani kinolinil, supstituirani 1,2,3,4-tetrahidrokinolinil, supstituirani izokinolinil, supstituirani 1,2,3,4-tetrahidroizokinolinil, supstituirani 9H-karbazolil, supstituirani kromanil, supstituirani indolil, supstituirani naftil, supstituirani oksazolil, supstituirani fenil, supstituirani fenil-C1-C7-alkil, supstituirani fenoksi-C1-C7-alkil, supstituirani fenil-C1-C7-alkoksi, supstituirani fenil-C2-C7-alkenil, supstituirani piridazinil, supstituirani piridinil, supstituirani piridinonil, supstituirani tetralinil i supstituirani tetralinonil zamijenjeni s R6, R7 i R8.
3. Spoj prema bilo kojem od zahtjeva 1 do 2, naznačen time, da je R2 odabran iz prstenastih sustava A i C.
4. Spoj prema bilo kojem od zahtjeva 1 do 3, naznačen time, da R2 predstavlja prstenasti sustav A.
5. Spoj prema bilo kojem od zahtjeva 1 do 4, naznačen time, da Y je -C(O)-.
6. Spoj prema bilo kojem od zahtjeva 1 do 5, naznačen time, da su R3, R4 i R5 neovisno odabrani od H i halogena.
7. Spoj prema bilo kojem od zahtjeva 1 do 6, naznačen time, da R6 je H, halogen, cijano, cijano-C1-C7-alkil, C1-C7-alkil, halo-C1-C7-alkil, C3-C8-cikloalkil-C1-C7-alkoksi, C1-C7-alkoksi, C1-C7-alkoksi-C1-C7-alkil, halo-C1-C7-alkoksi, C1-C7-alkoksi-C1-C7-alkoksi, fenil,
fenil-C1-C7-alkoksi ili fenil zamijenjen s jednim do tri halogena.
8. Spoj prema bilo kojem od zahtjeva 1 do 7, naznačen time, da R7 je H, halogen, C1-C7-alkil, C3-C8-cikloalkil, C1-C7-alkoksi, halo-C1-C7-alkoksi, C1-C7-alkilsulfonil, furanil ili tetrahidropiranil.
9. Spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time, da R8 je H ili C1-C7-alkil.
10. Spoj prema bilo kojem od zahtjeva 1 do 9, naznačen time, da je odabran iz skupine koju čine:
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-kloro-naftalen-2-il)-metanon;
1-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-3-(4-trifluorometoksi-fenil)-propan-1-on;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4'-fluoro-bifenil-4-il)-metanon;
(E)-1-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-3-(4-trifluorometoksi-fenil)-propenon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-bromo-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-metoksi-naftalen-2-il)-metanon;
(E)-1-[(3aS,3bS,6aR,6bR)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-3-(4-trifluorometoksi-fenil)-propenon;
6-[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-naftalen-2-karbonitril;
1-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-2-(4-trifluorometoksi-fenoksi)-etanon;
1-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-2-(2-izopropil-fenoksi)-etanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(5-trifluorometoksi-1H-indol-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-trifluorometoksi-1H-indol-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-naftalen-2-il-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-metil-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(7-metil-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-fenil-naftalen-2-il)-metanon;
(6-bromo-naftalen-2-il)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4'-kloro-bifenil-4-il)-metanon;
(4'-kloro-bifenil-4-il)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(5-trifluorometoksi-1H-indol-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-trifluorometoksi-1H-indol-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(3-metoksi-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-metoksi-naftalen-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1H-indol-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-metil-1H-indol-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-ciklopropilmetoksi-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-metoksi-naftalen-2-il)-metanon;
2-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-1H-indol-5-karbonitril;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(3-metoksi-fenil)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-metoksi-kinolin-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[2-(4-kloro-fenil)-5-metil-oksazol-4-il]-metanon;
[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1,2,3,4-tetrahidro-naftalen-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-metil-5-trifluorometoksi-1H-indol-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-kloro-1H-indol-2-il)-methanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-kloro-1-metil-1H-indol-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-metil-1H-indol-2-il)-metanon;
{2-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-indol-1-il}-acetonitril;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-izobutil-1H-indol-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-kinolin-2-il-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-izokinolin-3-il-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1H-indol-6-il)-metanon;
3-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-3,4-dihidro-2H-naftalen-1-on;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-kroman-2-il-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1H-indol-5-il)-metanon;
(4-metoksi-naftalen-2-il)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[6-(4-kloro-fenil)-piridin-3-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-metoksi-izokinolin-3-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-metil-kinolin-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(5-kloro-1H-indol-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[4-(2-metoksi-etoksi)-naftalen-2-il]-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(7-fenil-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-etoksi-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-izopropoksi-naftalen-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-benziloksi-1H-indol-6-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(5,6,7,8-tetrahidro-naftalen-2-il)-metanon;
[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4,4-dimetil-1,2,3,4-tetrahidro-naftalen-2-il)-metanon;
[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[1-(3-metoksi-propil)-1,2,3,4-tetrahidro-kinolin-3-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[1-(2-metoksi-etoksi)-izokinolin-3-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-ciklopropilmetoksi-izokinolin-3-il)-metanon;
(4-izopropoksi-naftalen-2-il)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[1-(2,2,2-trifluoro-etoksi)-izokinolin-3-il]-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-izopropoksi-1H-indol-6-il)-metanon;
4-[(3aS,3bS,6aR,6bR)-5-(4-izopropoksi-naftalen-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-benzen-sulfonamid;
[6-(4-kloro-fenil)-piridin-3-il]-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
(1-ciklopropilmetoksi-izokinolin-3-il)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-izopropoksi-1-metil-1H-indol-6-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-etoksi-kinolin-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-izopropoksi-kinolin-2-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-kloro-9H-karbazol-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[4-(2-metoksi-etoksi)-kinolin-2-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-izopropoksi-7-trifluorometil-kinolin-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-ciklopropilmetoksi-kinolin-2-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[5-(4-kloro-fenil)-piridin-2-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-etoksi-izokinolin-3-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1-etil-4-izopropoksi-1H-indol-6-il)-metanon;
6-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-3-(4-kloro-fenil)-1H-piridin-2-on;
1-[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(7-kloro-4-etoksi-kinolin-2-il)-metanon;
(7-kloro-4-etoksi-kinolin-2-il)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-izopropoksi-5,6,7,8-tetrahidro-naftalen-2-il)-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bR,6aS,6bR)-5-[4-(2-metoksi-etoksi)-7-trifluorometil-kinolin-2-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-[(3aS,3bR,6aS,6bR)-5-(4-etoksi-6-trifluorometil-kinolin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-etoksi-1-etil-1H-indol-5-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[1-etil-4-(2,2,2-trifluoro-etoksi)-1H-indol-5-il]-metanon;
5-[(3aS,3bR,6aS,6bR)-5-(4-etoksi-kinolin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-piridin-2-amid-sulfonska kiselina;
(1H-benzotriazol-5-il)-{(3aS,3bR,6aS,6bR)-5-[4-(2,2,2-trifluoro-etoksi)-kinolin-2-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[4-etoksi-1-(2,2,2-trifluoro-etil)-1H-indol-6-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-[(3aS,3bR,6aS,6bR)-5-(5-kloro-4-ciklopropilmetoksi-piridin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
(1H-benzotriazol-5-il)-[(3aS,3bR,6aS,6bR)-5-(5-ciklopropil-6-ciklopropilmetoksi-piridin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
(3,4-dimetil-fenil)-[(3aS,3bR,6aS,6bR)-5-(4-etoksi-5,6,7,8-tetrahidro-kinolin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
(1H-benzotriazol-5-il)-[(3aS,3bS,6aR,6bR)-5-(4'-kloro-bifenil-3-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
(1H-benzotriazol-5-il)-[(3aS,3bR,6aS,6bR)-5-(4-etoksi-7-metoksi-kinolin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aS,3bS,6aR,6bR)-5-(4-etoksi-6-trifluorometil-kinolin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1H-[1,2,3]triazolo[4,5-b]piridin-5-il)-metanon;
[(3aS,3bS,6aR,6bR)-5-(1-etoksi-izokinolin-3-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(1H-[1,2,3]triazolo[4,5-b]piridin-5-il)-metanon;
(1H-benzotriazol-5-il)-[(3aS,3bR,6aS,6bR)-5-(6-ciklopropilmetoksi-5-trifluorometil-piridin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bR,6a S,6bR)-5-[5-ciklopropil-4-(2,2,2-trifluoro-etoksi)-piridin-2-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bR,6aS,6bR)-5-[6-ciklopropil-5-(2,2,2-trifluoro-etoksi)-piridazin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon']dipirol-2-il}-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-kloro-4-etoksi-kinolin-2-il)-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bR,6a S,6bR)-5-[6-(2,2,2-trifluoro-etoksi)-5-trifluorometil-piridin-2-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bR,6aS,6bR)-5-[6-(2,2,2-trifluoro-etoksi)-piridin-2-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[5-bromo-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bR,6aS,6bR)-5-[5-(2,2,2-trifluoro-etoksi)-piridin-2-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
[(3aS,3bR,6aS,6bR)-5-(6-ciklopropilmetoksi-piridazin-3-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(3,4-dimetil-fenil)-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[5-bromo-2-metil-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[5-ciklopropil-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[6-(2,2,2-trifluoro-etoksi)-5-trifluorometil-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[5-(tetrahidropiran-4-il)-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bR,6aS,6bR)-5-[4-(4-kloro-fenil)-5-(2,2,2-trifluoro-etoksi)-piridin-2-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[5-furan-2-il-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[5-kloro-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
[(3aS,3bR,6aS,6bR)-5-(4-etoksi-kinolin-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-fluoro-1H-benzotriazol-5-il)-metanon;
{(3aS,3bS,6aR,6bR)-5-[5-metansulfonil-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-fenil-metanon;
(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karboksilna kiselina-4-trifluorometoksi-benzilester;
(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karboksilna kiselina-3,5-dikloro-benzilester;
(1H-benzotriazol-5-il)-[(3aS,3bR,6aS,6bR)-5-(4'-fluoro-bifenil-4-sulfonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
(1H-benzotriazol-5-il)-[(3aS,3bR,6aS,6bR)-5-(6-kloro-naftalen-2-sulfonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(6-trifluorometil-3,4-dihidro-1H-izokinolin-2-il)-metanon;
i njihove farmaceutski prihvatljive soli.
11. Spoj prema bilo kojem od zahtjeva 1 do 10, naznačen time, da je odabran iz skupine koju čine:
(E)-1-[(3aS,3bR,6aS,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-3-(4-trifluorometoksi-fenil)-propenon;
(4-izopropoksi-naftalen-2-il)-[(3aR,3bS,6aR,6bS)-5-((R)-4,5,6,7-tetrahidro-1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-metanon;
4-[(3aS,3bS,6aR,6bR)-5-(4-izopropoksi-naftalen-2-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karbonil]-benzensulfonamid;
[(3aS,3bS,6aR,6bR)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-(4-izopropoksi-1-metil-1H-indol-6-il)-metanon;
[(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il]-[4-(2-metoksi-etoksi)-kinolin-2-il]-metanon;
(1H-benzotriazol-5-il)-{(3aS,3bS,6aR,6bR)-5-[5-bromo-6-(2,2,2-trifluoro-etoksi)-piridin-3-karbonil]-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-il}-metanon;
(3aR,3bS,6aR,6bS)-5-(1H-benzotriazol-5-karbonil)-oktahidro-ciklobuta[1,2-c;3,4-c']dipirol-2-karboksilna kiselina-4-trifluorometoksi-benzilester;
i njihove farmaceutski prihvatljive soli.
12. Postupak za proizvodnju spoja prema bilo kojem od zahtjeva 1 do 11, naznačen time, da obuhvaća reakciju spoja formule (II) u prisutnosti spoja formule (III), pri čemu R1, R2, A i Y imaju gore definirano značenje.
[image]
13. Spoj prema bilo kojem od zahtjeva 1 do 11, naznačen time, da se upotrebljava kao terapeutski djelatna tvar.
14. Farmaceutski pripravak, naznačen time, da obuhvaća spoj prema bilo kojem od zahtjeva 1 do 11 i terapeutski inertni nosač.
15. Spoj prema bilo kojem od zahtjeva 1 do 11, naznačen time, da se upotrebljava u liječenju ili profilaksi bubrežnih i jetrenih bolesnih stanja, upalnih stanja, poremećaja živčanog sustava, bolesti dišnog sustava, vaskularnih i kardiovaskularnih bolesnih stanja, fibrotičkih bolesti, raka, očnih bolesti, metaboličkih bolesti, kolestatskog i drugih oblika kroničnog pruritusa te akutnog i kroničnog odbacivanja transplantiranog organa.
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