HRP20150159T1 - Novi spojevi koji se vežu za fxr (nr1h4) i moduliraju njegovu aktivnost - Google Patents
Novi spojevi koji se vežu za fxr (nr1h4) i moduliraju njegovu aktivnost Download PDFInfo
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- HRP20150159T1 HRP20150159T1 HRP20150159TT HRP20150159T HRP20150159T1 HR P20150159 T1 HRP20150159 T1 HR P20150159T1 HR P20150159T T HRP20150159T T HR P20150159TT HR P20150159 T HRP20150159 T HR P20150159T HR P20150159 T1 HRP20150159 T1 HR P20150159T1
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- Prior art keywords
- cyclopropyl
- phenyl
- prophylaxis
- treatment
- methoxy
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- 150000001875 compounds Chemical class 0.000 title claims 13
- 230000000694 effects Effects 0.000 title claims 3
- 238000011321 prophylaxis Methods 0.000 claims 30
- 238000011282 treatment Methods 0.000 claims 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 12
- 229910052736 halogen Inorganic materials 0.000 claims 10
- 150000002367 halogens Chemical class 0.000 claims 10
- 230000001684 chronic effect Effects 0.000 claims 9
- 230000001587 cholestatic effect Effects 0.000 claims 8
- 229910052739 hydrogen Inorganic materials 0.000 claims 8
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 208000019425 cirrhosis of liver Diseases 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 6
- 208000035475 disorder Diseases 0.000 claims 6
- 210000004185 liver Anatomy 0.000 claims 6
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 4
- 206010012601 diabetes mellitus Diseases 0.000 claims 4
- 230000003176 fibrotic effect Effects 0.000 claims 4
- 239000001257 hydrogen Substances 0.000 claims 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 4
- 230000003463 hyperproliferative effect Effects 0.000 claims 4
- 150000002632 lipids Chemical class 0.000 claims 4
- 230000003211 malignant effect Effects 0.000 claims 4
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 4
- 230000000414 obstructive effect Effects 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 125000000335 thiazolyl group Chemical group 0.000 claims 4
- 125000001544 thienyl group Chemical group 0.000 claims 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- -1 4-(2-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)cyclopropyl)benzamido Chemical group 0.000 claims 2
- 208000007788 Acute Liver Failure Diseases 0.000 claims 2
- 206010000804 Acute hepatic failure Diseases 0.000 claims 2
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims 2
- 201000001320 Atherosclerosis Diseases 0.000 claims 2
- 208000023514 Barrett esophagus Diseases 0.000 claims 2
- 208000023665 Barrett oesophagus Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- 206010048832 Colon adenoma Diseases 0.000 claims 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 2
- 206010012689 Diabetic retinopathy Diseases 0.000 claims 2
- 208000032928 Dyslipidaemia Diseases 0.000 claims 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 208000004930 Fatty Liver Diseases 0.000 claims 2
- 206010019663 Hepatic failure Diseases 0.000 claims 2
- 206010019708 Hepatic steatosis Diseases 0.000 claims 2
- 206010019799 Hepatitis viral Diseases 0.000 claims 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims 2
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 2
- 102000004895 Lipoproteins Human genes 0.000 claims 2
- 108090001030 Lipoproteins Proteins 0.000 claims 2
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 2
- 208000008589 Obesity Diseases 0.000 claims 2
- 208000006011 Stroke Diseases 0.000 claims 2
- 208000007536 Thrombosis Diseases 0.000 claims 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims 2
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 2
- 238000009825 accumulation Methods 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 230000004913 activation Effects 0.000 claims 2
- 230000001154 acute effect Effects 0.000 claims 2
- 231100000836 acute liver failure Toxicity 0.000 claims 2
- 206010000891 acute myocardial infarction Diseases 0.000 claims 2
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims 2
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims 2
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 claims 2
- 238000002512 chemotherapy Methods 0.000 claims 2
- 201000010897 colon adenocarcinoma Diseases 0.000 claims 2
- 208000029742 colonic neoplasm Diseases 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 230000007850 degeneration Effects 0.000 claims 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 125000002541 furyl group Chemical group 0.000 claims 2
- 210000001035 gastrointestinal tract Anatomy 0.000 claims 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims 2
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims 2
- 125000001041 indolyl group Chemical group 0.000 claims 2
- 230000002757 inflammatory effect Effects 0.000 claims 2
- 208000028867 ischemia Diseases 0.000 claims 2
- 208000019423 liver disease Diseases 0.000 claims 2
- 231100000835 liver failure Toxicity 0.000 claims 2
- 208000007903 liver failure Diseases 0.000 claims 2
- 230000007774 longterm Effects 0.000 claims 2
- 230000001404 mediated effect Effects 0.000 claims 2
- 230000001613 neoplastic effect Effects 0.000 claims 2
- 235000020824 obesity Nutrition 0.000 claims 2
- 210000000056 organ Anatomy 0.000 claims 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims 2
- 230000037361 pathway Effects 0.000 claims 2
- 208000015768 polyposis Diseases 0.000 claims 2
- 230000002206 pro-fibrotic effect Effects 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- 238000001356 surgical procedure Methods 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 125000003831 tetrazolyl group Chemical group 0.000 claims 2
- 150000003626 triacylglycerols Chemical class 0.000 claims 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 2
- 201000001862 viral hepatitis Diseases 0.000 claims 2
- 125000006677 (C1-C3) haloalkoxy group Chemical group 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims 1
- KCIHDFUMQGXFFF-UHFFFAOYSA-N 2-[[4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]cyclopropyl]benzoyl]amino]ethanesulfonic acid Chemical compound C1=CC(C(=O)NCCS(=O)(=O)O)=CC=C1C1C(C=2C(=CC(OCC3=C(ON=C3C=3C(=CC=CC=3Cl)Cl)C3CC3)=CC=2)Cl)C1 KCIHDFUMQGXFFF-UHFFFAOYSA-N 0.000 claims 1
- HWOXGSYLOCRIMO-UHFFFAOYSA-N 3-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]cyclopropyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(C2C(C2)C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)Cl)=C1 HWOXGSYLOCRIMO-UHFFFAOYSA-N 0.000 claims 1
- XBUXXJUEBFDQHD-UHFFFAOYSA-N 4-[2-[2-chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]cyclopropyl]benzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1C(C=2C(=CC(OCC=3C(=NOC=3C3CC3)C=3C(=CC=CC=3Cl)Cl)=CC=2)Cl)C1 XBUXXJUEBFDQHD-UHFFFAOYSA-N 0.000 claims 1
- 229910006069 SO3H Inorganic materials 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
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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
- A61K31/41—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
- A61K31/4192—1,2,3-Triazoles
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- 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
- A61K31/42—Oxazoles
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- 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
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
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- 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
- A61K31/42—Oxazoles
- A61K31/423—Oxazoles condensed with carbocyclic rings
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- 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
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- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
- C07D261/08—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
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- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Claims (15)
1. Spoj prema slijedećoj formuli (1), njegov enantiomer, diastereomer, tautomer ili farmaceutski prihvatljiva sol
[image]
gdje
R je izabran iz grupe koju čini COOR6, CONR7R8, tetrazolil ili H, gdje je R6 nezavisno izabran iz grupe koju čini H, ili C1-6 alkil, i R7 i R8 međusobno nezavisno izabrani iz grupe koju čine H, C1-6 alkil, C1-6 haloalkil, C1-6 alkilen-R9, SO2-C1-6 alkil gdje je R9 izabran iz grupe koju čine COOH, OH, ili SO3H;
A je izabran iz grupe koju čine fenil, piridil, pirazolil, indolil, tienil, benzotienil, indazolil, benzizoksazolil, benzofuranil, benzotriazolil, furanil, benzotiazolil, tiazolil, svaki izborno supstituiran sa jednom ili dvije grupe nezavisno izabrane iz grupe koju čine OH, C1-6 alkil,
C3-6 cikloalkil, ili halogen;
Q je izabran iz grupe koju čine fenil, piridil, tiazolil, tiofenil, pirimidil, svaki izborno supstituiran sa jednom ili dvije grupe nezavisno izabrane iz grupe koju čini C1-6 alkil, halogen ili CF3;
[image]
gdje
X= CH, N, NO;
R1 je izabran iz grupe koju čine vodik, C1-C3 alkil, C3-C6 cikloalkil, C4-C5 alkilcikloalkil, gdje C1-3 alkil je izborno supstituiran sa 1 do 3 supstituenta nezavisno izabrana od halogena, hidroksi ili C1-6 alkoksi;
R2 i R3 su nezavisno izabrani iz grupe koju čini vodik, C1-C3 alkil, C1-C3 haloalkil, C1-C3 alkoksi, C1-C3 haloalkoksi i halogen.
2. Spoj prema patentnom zahtjevu 1
gdje
R je izabran iz grupe koju čini COOR6, CONR7R8, tetrazolil ili H, sa R6, R7 i R8 nezavisno izabran iz grupe koju čini H i C1-6 alkil;
A je izabran iz grupe koju čini fenil, piridil, indolil, tienil, benzotienil, indazolil, benzizoksazolil, benzofuranil, benzotriazolil, furanil, benzotiazolil, tiazolil, svaki izborno supstituiran sa jednom ili dvije grupe nezavisno izabran iz grupe koju čini OH, C1-6 alkil i C3-6 cikloalkil;
Q je izabrani iz grupe koju čini fenil, piridil, tiazolil, tiofenil, pirimidil, svaki izborno supstituiran sa jednom ili dvije grupe nezavisno izabran iz grupe koju čini C1-6 alkil, halogen i CF3;
[image]
gdje
X= CH, N, NO;
R1 je izabran iz grupe koju čini vodik, C1-C3 alkil, C1-C3 haloalkil, C3-C6 cikloalkil i C4-C5 alkilcikloalkil;
R2 i R3 su nezavisno izabrani iz grupe koju čini vodik, C1-C3 alkil, C1-C3 haloalkil, C1-C3 alkoksi, C1-C3 haloalkoksi i halogen.
3. Spoj prema patentnom zahtjevu 1 ili 2, sa slijedećom strukturom
[image]
gdje
X1 je CH ili N;
R4 i R5 su nezavisno izabrani iz grupe koju čini H, C1-6 alkil, halogen i CF3;
R-A je izabran od
[image]
ili
R1 je izabran iz grupe koju čini izopropil, t-butil i ciklopropil;
R2 i R3 su nezavisno izabrani iz grupe koju čini halogen, C1-C3 alkil, metoksi i trifluorometoksi.
4. Spoj prema bilo kojem od patentnih zahtjeva 1 do 3, gdje
A je fenil;
Q je izborno supstituiran fenil, poželjno supstituiran sa jednim supstituentom, poželjno halogenom;
X je CH;
R1 je cikloalkil; i
R2 i R3 svaki su halogen.
5. Spoj prema bilo kojem od patentnih zahtjeva 1 do 4 izabran od:
3-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
(-)-3-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
(+)-3-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
3-((2-(2-kloro-4-((3-(2,6-diklorofenil)-5-izopropilizoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
3-((2-(2-kloro-4-((5-ciklopropil-3-(3,5-dikloropiridin-4-il)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
4-((4-((4-(2-(3-carboksifenil)ciklopropil)-3-klorofenoksi)metil)-5-ciklopropilizoksazol-3-il)-3,5-dikloropiridin 1-oksida
3-((2-(2-kloro-4-((1-(2,6-diklorofenil)-4-izopropil-1H-1,2,3-triazol-5-il)metoksi)fenil)ciklopropil)benzojeve kiseline
4-(((4-(2-(6-(1H-tetrazol-5-il)piridin-3-il)ciklopropil)-3-klorofenoksi)metil)-5-ciklopropil-3-(2,6-diklorofenil)izoksazola
5-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)pikolinske kiseline.
6. Spoj prema bilo kojem od patentnih zahtjeva 1 do 4 izabran od
3-((2-(6-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)-2-(trifluorometil)piridin-3-il)ciklopropil)benzojeve kiseline
4-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
1,3-dihidroksi-2-(hidroksimetil)propan-2-aminij 4-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzoata
(+)-4-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
(-)-4-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
6-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)-1-metil-1H-indazol-3-karboksilne kiseline
(+)-6-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)-1-metil-1H-indazol-3-karboksilne kiseline
(-)-6-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)-1-metil-1H-indazol-3-karboksilne kiseline
4-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)-N-(metilsulfonil)benzamida
2-((4-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzamido)etansulfo kiseline
4-(((4-(2-(4-(1H-tetrazol-5-il)fenil)ciklopropil)-3-kloropenoksi)metil)-5-ciklopropil-3-(2,6-diklorofenil)izoksazola
4-((2-(2-kloro-4-((3-(2,6-diklorofenil)-5-(2-hidroksipropan-2-il)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
5-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)-1-izopropil-1H-pirazol-3-karboksilne kiseline
6-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)-1-izopropil-1H-indazol-3-karboksilne kiseline
4-((2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)-2,6-dimetilbenzojeve kiseline
4-((2-(2-kloro-4-((5-ciklopropil-3-(2-(trifluorometoksi)fenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzojeve kiseline
(+)-2-(4-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzamido)etansulfo kiseline
(-)-2-((4-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzamido)etansulfo kiseline
2-((4-(2-(2-kloro-4-((5-ciklopropil-3-(2,6-diklorofenil)izoksazol-4-il)metoksi)fenil)ciklopropil)benzamido)octene kiseline
4-((2-(2-kloro-4-((4-(2,6-diklorofenil)-1-izopropil-1H-1,2,3-triazol-5-il)metoksi)fenil)ciklopropil)benzojeve kiseline.
7. Spoj prema bilo kojem od patentnih zahtjeva 1 do 6 za korištenje u profilaksi i/ili tretmanu bolesti posredovanih sa FXR.
8. Spoj prema patentnom zahtjevu 7 za uporabu u profilaksi i/ili tretmanu intrahepatičkog ili nekih drugih oblika ekstrahepatičkih holestatičnih stanja, ili fibroze jetre koja je rezultat kroničnih holestatičnih stanja ili akutnih intrahepatičkih holestatičnih stanja; i/ili
za uporabu u profilaksi i/ili tretmanu opstruktivnih ili kroničnih inflamatornih bolesti jetre; i/ili
za uporabu u profilaksi i/ili tretmanu ciroze jetre; i/ili
za uporabu u profilaksi i/ili tretmanu steatoze jetre i povezanih sindroma, holestatičnih ili fibrotičkih efekata koji su povezani sa cirozom jetre izazvane alkoholom ili virusnim oblikom hepatitisa; i/ili
za uporabu u profilaksi i/ili liječenju otkazivanja jetre ili ishemije jetre nakon velike kirurške intervencije na jetre; i/ili
za uporabu u profilaksi i/ili tretmanu steatohepatitisa povezanog sa kemoterapijom (CASH); i/ili
za uporabu u profilaksi i/ili tretmanu akutnog otkazivanja jetre; i/ili
za uporabu u profilaksi i/ili tretmanu inflamatorne bolesti crijeva.
9. Spoj prema patentnom zahtjevu 7 za uporabu u profilaksi i/ili tretmanu poremećaja lipida i lipoproteina; i/ili
za uporabu u profilaksi i/ili tretmanu dijabetesa tipa II i kliničkih komplikacija tipa I i tipa II dijabetesa, uključujući dijabetičku nefropatiju, dijabetičku neuropatiju, dijabetičku retinopatiju i druge uočene efekte klinički manifestirane kod dugotrajnog dijabetesa; i/ili
za uporabu u profilaksi i/ili tretmanu stanja i bolesti koji rezultiraju iz kronične masne i fibrotičke degeneracije organa uslijed akumulacije lipida i specifično triglicerida i naknadne aktivacije profibrotičkih puteva, kao što je bolest ne-alkoholna masna jetra (NAFLD), ili ne-alkoholni steatohepatitis (NASH); i/ili
za uporabu u profilaksi i/ili tretmanu debljine ili metaboličkog sindroma (kombinirana stanja dislipidemije, dijabetesa ili abnormalno visokog indeksa tjelesne mase); i/ili
za uporabu u profilaksi i/ili tretmanu akutnog infarkta miokarda, akutnog moždanog udara, ili tromboze koja se dešava kao krajnji ishod kronične opstruktivne ateroskleroze.
10. Spoj prema patentnom zahtjevu 7 za uporabu u profilaksi i/ili tretmanu ne-malignih hiperproliferativnih poremećaja i malignih hiperproliferativnih poremećaja, specifično hepatocelularnog karcinoma, adenoma debelog crijeva i polipoze, adenokarcinoma debelog crijeva, raka dojke, adenokarcinoma pankreasa, Barrett-ovog ezofagusa i drugih oblika neoplastičnih bolesti gastrointestinalnog trakta i jetre.
11. Uporaba spoja prema bilo kojem od patentnih zahtjeva 1 do 6 za pripremu medikamenta za profilaksu i/ili tretman bolesti posredovanih sa FXR.
12. Uporaba prema patentnom zahtjevu 11 za profilaksu i/ili tretman kroničnih intrahepatičkih ili nekih drugih ekstrahepatičkih holestatičnih stanja, ili fibroze jetre koja je rezultat kroničnih holestatičnih stanja ili akutnih holestatičnih stanja; i/ili
za uporabu u profilaksi i/ili tretmanu opstruktivnih ili kroničnih inflamatornih bolesti jetre; i/ili
za uporabu u profilaksi i/ili tretmanu ciroze jetre; i/ili
za uporabu u profilaksi i/ili tretmanu steatoze jetre i povezanih sindroma, holestatičnih ili fibrotičkih efekata koji su povezani sa cirozom jetre izazvane alkoholom ili virusnim oblikom hepatitisa; i/ili
za uporabu u profilaksi i/ili liječenju otkazivanja jetre ili ishemije jetre nakon velike kirurške intervencije na jetre; i/ili
za uporabu u profilaksi i/ili tretmanu steatohepatitisa povezanog sa kemoterapijom (CASH); i/ili
za uporabu u profilaksi i/ili tretmanu akutnog otkazivanja jetre; i/ili
za uporabu u profilaksi i/ili tretmanu inflamatorne bolesti crijeva.
13. Uporaba prema patentnom zahtjevu 11 za profilaksu i/ili tretman poremećaja lipida ili lipoproteina; i/ili
za uporabu u profilaksi i/ili tretmanu dijabetesa tipa II i kliničkih komplikacija tipa I i tipa II dijabetesa, uključujući dijabetičku nefropatiju, dijabetičku neuropatiju, dijabetičku retinopatiju i druge uočene efekte klinički manifestirane kod dugotrajnog dijabetesa; i/ili
za uporabu u profilaksi i/ili tretmanu stanja i bolesti koji rezultiraju iz kronične masne i fibrotičke degeneracije organa uslijed akumulacije lipida i specifično triglicerida i naknadne aktivacije profibrotičkih puteva, kao što je bolest ne-alkoholna masna jetra (NAFLD), ili ne-alkoholni steatohepatitis (NASH); i/ili
za uporabu u profilaksi i/ili tretmanu debljine ili metaboličkog sindroma (kombinirana stanja dislipidemije, dijabetesa ili abnormalno visokog indeksa tjelesnemase); i/ili
za uporabu u profilaksi i/ili tretmanu akutnog infarkta miokarda, akutnog moždanog udara, ili tromboze koja se dešava kao krajnji ishod kronične opstruktivne ateroskleroze.
14. Uporaba prema patentnom zahtjevu 11 za profilaksu i/ili tretman ne-malignih hiperproliferativnih poremećaja i malignih hiperproliferativnih poremećaja, specifično hepatocelularnog karcinoma, adenoma debelog crijeva i polipoze, adenokarcinoma debelog crijeva, raka dojke, adenokarcinoma pankreasa, Barrett-ovog ezofagusa i drugih oblika neoplastičnih bolesti gastrointestinalnog trakta i jetre.
15. Spoj prema bilo kojem od patentnih zahtjeva 1 do 6 za uporabu kao medikamenta.
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| US23511709P | 2009-08-19 | 2009-08-19 | |
| EP09010676A EP2289883A1 (en) | 2009-08-19 | 2009-08-19 | Novel FXR (NR1H4) binding and activity modulating compounds |
| EP10747171.6A EP2467366B1 (en) | 2009-08-19 | 2010-08-19 | Novel fxr (nr1h4) binding and activity modulating compounds |
| PCT/EP2010/005093 WO2011020615A1 (en) | 2009-08-19 | 2010-08-19 | Novel fxr (nr1h4 ) binding and activity modulating compounds |
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