HRP20191292T1 - Derivati fgf21 i njihova upotreba - Google Patents
Derivati fgf21 i njihova upotreba Download PDFInfo
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- HRP20191292T1 HRP20191292T1 HRP20191292TT HRP20191292T HRP20191292T1 HR P20191292 T1 HRP20191292 T1 HR P20191292T1 HR P20191292T T HRP20191292T T HR P20191292TT HR P20191292 T HRP20191292 T HR P20191292T HR P20191292 T1 HRP20191292 T1 HR P20191292T1
- Authority
- HR
- Croatia
- Prior art keywords
- ethoxy
- amino
- ethylamino
- acetyl
- fgf21
- Prior art date
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- 108090000376 Fibroblast growth factor 21 Proteins 0.000 title claims 48
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 title claims 48
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims 148
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 108
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 60
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 58
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 29
- 102000004169 proteins and genes Human genes 0.000 claims 8
- 108090000623 proteins and genes Proteins 0.000 claims 8
- 101000846529 Homo sapiens Fibroblast growth factor 21 Proteins 0.000 claims 7
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims 7
- 102000056713 human FGF21 Human genes 0.000 claims 7
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 5
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 5
- 239000005711 Benzoic acid Substances 0.000 claims 3
- 150000001413 amino acids Chemical class 0.000 claims 3
- 235000010233 benzoic acid Nutrition 0.000 claims 3
- 230000008878 coupling Effects 0.000 claims 3
- 238000010168 coupling process Methods 0.000 claims 3
- 238000005859 coupling reaction Methods 0.000 claims 3
- 206010012601 diabetes mellitus Diseases 0.000 claims 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 claims 2
- GLGNXYJARSMNGJ-VKTIVEEGSA-N (1s,2s,3r,4r)-3-[[5-chloro-2-[(1-ethyl-6-methoxy-2-oxo-4,5-dihydro-3h-1-benzazepin-7-yl)amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide Chemical compound CCN1C(=O)CCCC2=C(OC)C(NC=3N=C(C(=CN=3)Cl)N[C@H]3[C@H]([C@@]4([H])C[C@@]3(C=C4)[H])C(N)=O)=CC=C21 GLGNXYJARSMNGJ-VKTIVEEGSA-N 0.000 claims 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 claims 2
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 claims 2
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 claims 2
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 claims 2
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 claims 2
- 229940126657 Compound 17 Drugs 0.000 claims 2
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims 2
- LNUFLCYMSVYYNW-ZPJMAFJPSA-N [(2r,3r,4s,5r,6r)-2-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[(2r,3r,4s,5r,6r)-6-[[(3s,5s,8r,9s,10s,13r,14s,17r)-10,13-dimethyl-17-[(2r)-6-methylheptan-2-yl]-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-3-yl]oxy]-4,5-disulfo Chemical compound O([C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1[C@@H](COS(O)(=O)=O)O[C@H]([C@@H]([C@H]1OS(O)(=O)=O)OS(O)(=O)=O)O[C@@H]1C[C@@H]2CC[C@H]3[C@@H]4CC[C@@H]([C@]4(CC[C@@H]3[C@@]2(C)CC1)C)[C@H](C)CCCC(C)C)[C@H]1O[C@H](COS(O)(=O)=O)[C@@H](OS(O)(=O)=O)[C@H](OS(O)(=O)=O)[C@H]1OS(O)(=O)=O LNUFLCYMSVYYNW-ZPJMAFJPSA-N 0.000 claims 2
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 claims 2
- KGNDCEVUMONOKF-UGPLYTSKSA-N benzyl n-[(2r)-1-[(2s,4r)-2-[[(2s)-6-amino-1-(1,3-benzoxazol-2-yl)-1,1-dihydroxyhexan-2-yl]carbamoyl]-4-[(4-methylphenyl)methoxy]pyrrolidin-1-yl]-1-oxo-4-phenylbutan-2-yl]carbamate Chemical compound C1=CC(C)=CC=C1CO[C@H]1CN(C(=O)[C@@H](CCC=2C=CC=CC=2)NC(=O)OCC=2C=CC=CC=2)[C@H](C(=O)N[C@@H](CCCCN)C(O)(O)C=2OC3=CC=CC=C3N=2)C1 KGNDCEVUMONOKF-UGPLYTSKSA-N 0.000 claims 2
- 229940126543 compound 14 Drugs 0.000 claims 2
- 229940125758 compound 15 Drugs 0.000 claims 2
- 229940126142 compound 16 Drugs 0.000 claims 2
- 229940125810 compound 20 Drugs 0.000 claims 2
- 229940126086 compound 21 Drugs 0.000 claims 2
- 229940126208 compound 22 Drugs 0.000 claims 2
- 229940125833 compound 23 Drugs 0.000 claims 2
- 229940125961 compound 24 Drugs 0.000 claims 2
- 150000001875 compounds Chemical class 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- JAXFJECJQZDFJS-XHEPKHHKSA-N gtpl8555 Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@@H]1C(=O)N[C@H](B1O[C@@]2(C)[C@H]3C[C@H](C3(C)C)C[C@H]2O1)CCC1=CC=C(F)C=C1 JAXFJECJQZDFJS-XHEPKHHKSA-N 0.000 claims 2
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- 125000006296 sulfonyl amino group Chemical group [H]N(*)S(*)(=O)=O 0.000 claims 2
- ASGMFNBUXDJWJJ-JLCFBVMHSA-N (1R,3R)-3-[[3-bromo-1-[4-(5-methyl-1,3,4-thiadiazol-2-yl)phenyl]pyrazolo[3,4-d]pyrimidin-6-yl]amino]-N,1-dimethylcyclopentane-1-carboxamide Chemical compound BrC1=NN(C2=NC(=NC=C21)N[C@H]1C[C@@](CC1)(C(=O)NC)C)C1=CC=C(C=C1)C=1SC(=NN=1)C ASGMFNBUXDJWJJ-JLCFBVMHSA-N 0.000 claims 1
- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 claims 1
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 claims 1
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 claims 1
- VIJSPAIQWVPKQZ-BLECARSGSA-N (2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-[[(2s)-2-acetamido-5-(diaminomethylideneamino)pentanoyl]amino]-4-methylpentanoyl]amino]-4,4-dimethylpentanoyl]amino]-4-methylpentanoyl]amino]propanoyl]amino]-5-(diaminomethylideneamino)pentanoic acid Chemical compound NC(=N)NCCC[C@@H](C(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(C)=O VIJSPAIQWVPKQZ-BLECARSGSA-N 0.000 claims 1
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 claims 1
- HUWSZNZAROKDRZ-RRLWZMAJSA-N (3r,4r)-3-azaniumyl-5-[[(2s,3r)-1-[(2s)-2,3-dicarboxypyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl]amino]-5-oxo-4-sulfanylpentane-1-sulfonate Chemical compound OS(=O)(=O)CC[C@@H](N)[C@@H](S)C(=O)N[C@@H]([C@H](C)CC)C(=O)N1CCC(C(O)=O)[C@H]1C(O)=O HUWSZNZAROKDRZ-RRLWZMAJSA-N 0.000 claims 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 claims 1
- YQOLEILXOBUDMU-KRWDZBQOSA-N (4R)-5-[(6-bromo-3-methyl-2-pyrrolidin-1-ylquinoline-4-carbonyl)amino]-4-(2-chlorophenyl)pentanoic acid Chemical compound CC1=C(C2=C(C=CC(=C2)Br)N=C1N3CCCC3)C(=O)NC[C@H](CCC(=O)O)C4=CC=CC=C4Cl YQOLEILXOBUDMU-KRWDZBQOSA-N 0.000 claims 1
- FQMZXMVHHKXGTM-UHFFFAOYSA-N 2-(1-adamantyl)-n-[2-[2-(2-hydroxyethylamino)ethylamino]quinolin-5-yl]acetamide Chemical compound C1C(C2)CC(C3)CC2CC13CC(=O)NC1=CC=CC2=NC(NCCNCCO)=CC=C21 FQMZXMVHHKXGTM-UHFFFAOYSA-N 0.000 claims 1
- PYRKKGOKRMZEIT-UHFFFAOYSA-N 2-[6-(2-cyclopropylethoxy)-9-(2-hydroxy-2-methylpropyl)-1h-phenanthro[9,10-d]imidazol-2-yl]-5-fluorobenzene-1,3-dicarbonitrile Chemical compound C1=C2C3=CC(CC(C)(O)C)=CC=C3C=3NC(C=4C(=CC(F)=CC=4C#N)C#N)=NC=3C2=CC=C1OCCC1CC1 PYRKKGOKRMZEIT-UHFFFAOYSA-N 0.000 claims 1
- LFOIDLOIBZFWDO-UHFFFAOYSA-N 2-methoxy-6-[6-methoxy-4-[(3-phenylmethoxyphenyl)methoxy]-1-benzofuran-2-yl]imidazo[2,1-b][1,3,4]thiadiazole Chemical compound N1=C2SC(OC)=NN2C=C1C(OC1=CC(OC)=C2)=CC1=C2OCC(C=1)=CC=CC=1OCC1=CC=CC=C1 LFOIDLOIBZFWDO-UHFFFAOYSA-N 0.000 claims 1
- WYFCZWSWFGJODV-MIANJLSGSA-N 4-[[(1s)-2-[(e)-3-[3-chloro-2-fluoro-6-(tetrazol-1-yl)phenyl]prop-2-enoyl]-5-(4-methyl-2-oxopiperazin-1-yl)-3,4-dihydro-1h-isoquinoline-1-carbonyl]amino]benzoic acid Chemical compound O=C1CN(C)CCN1C1=CC=CC2=C1CCN(C(=O)\C=C\C=1C(=CC=C(Cl)C=1F)N1N=NN=C1)[C@@H]2C(=O)NC1=CC=C(C(O)=O)C=C1 WYFCZWSWFGJODV-MIANJLSGSA-N 0.000 claims 1
- HCCNBKFJYUWLEX-UHFFFAOYSA-N 7-(6-methoxypyridin-3-yl)-1-(2-propoxyethyl)-3-(pyrazin-2-ylmethylamino)pyrido[3,4-b]pyrazin-2-one Chemical compound O=C1N(CCOCCC)C2=CC(C=3C=NC(OC)=CC=3)=NC=C2N=C1NCC1=CN=CC=N1 HCCNBKFJYUWLEX-UHFFFAOYSA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 claims 1
- 229940127007 Compound 39 Drugs 0.000 claims 1
- 208000030814 Eating disease Diseases 0.000 claims 1
- 208000019454 Feeding and Eating disease Diseases 0.000 claims 1
- 206010019708 Hepatic steatosis Diseases 0.000 claims 1
- 208000008589 Obesity Diseases 0.000 claims 1
- SPXSEZMVRJLHQG-XMMPIXPASA-N [(2R)-1-[[4-[(3-phenylmethoxyphenoxy)methyl]phenyl]methyl]pyrrolidin-2-yl]methanol Chemical compound C(C1=CC=CC=C1)OC=1C=C(OCC2=CC=C(CN3[C@H](CCC3)CO)C=C2)C=CC=1 SPXSEZMVRJLHQG-XMMPIXPASA-N 0.000 claims 1
- PSLUFJFHTBIXMW-WYEYVKMPSA-N [(3r,4ar,5s,6s,6as,10s,10ar,10bs)-3-ethenyl-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-6-(2-pyridin-2-ylethylcarbamoyloxy)-5,6,6a,8,9,10-hexahydro-2h-benzo[f]chromen-5-yl] acetate Chemical compound O([C@@H]1[C@@H]([C@]2(O[C@](C)(CC(=O)[C@]2(O)[C@@]2(C)[C@@H](O)CCC(C)(C)[C@@H]21)C=C)C)OC(=O)C)C(=O)NCCC1=CC=CC=N1 PSLUFJFHTBIXMW-WYEYVKMPSA-N 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 claims 1
- 229940125878 compound 36 Drugs 0.000 claims 1
- 229940125807 compound 37 Drugs 0.000 claims 1
- 229940127573 compound 38 Drugs 0.000 claims 1
- 229940126540 compound 41 Drugs 0.000 claims 1
- 229940125844 compound 46 Drugs 0.000 claims 1
- 229940127271 compound 49 Drugs 0.000 claims 1
- 229940126545 compound 53 Drugs 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 235000014632 disordered eating Nutrition 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 150000002148 esters Chemical class 0.000 claims 1
- 125000005647 linker group Chemical group 0.000 claims 1
- 150000002632 lipids Chemical class 0.000 claims 1
- RENRQMCACQEWFC-UGKGYDQZSA-N lnp023 Chemical compound C1([C@H]2N(CC=3C=4C=CNC=4C(C)=CC=3OC)CC[C@@H](C2)OCC)=CC=C(C(O)=O)C=C1 RENRQMCACQEWFC-UGKGYDQZSA-N 0.000 claims 1
- IOMMMLWIABWRKL-WUTDNEBXSA-N nazartinib Chemical compound C1N(C(=O)/C=C/CN(C)C)CCCC[C@H]1N1C2=C(Cl)C=CC=C2N=C1NC(=O)C1=CC=NC(C)=C1 IOMMMLWIABWRKL-WUTDNEBXSA-N 0.000 claims 1
- 235000020824 obesity Nutrition 0.000 claims 1
- PIDFDZJZLOTZTM-KHVQSSSXSA-N ombitasvir Chemical compound COC(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1C(=O)NC1=CC=C([C@H]2N([C@@H](CC2)C=2C=CC(NC(=O)[C@H]3N(CCC3)C(=O)[C@@H](NC(=O)OC)C(C)C)=CC=2)C=2C=CC(=CC=2)C(C)(C)C)C=C1 PIDFDZJZLOTZTM-KHVQSSSXSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1825—Fibroblast growth factor [FGF]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
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Claims (18)
1. Derivat proteina FGF21,
naznačen time što navedeni protein sadrži ostatak Cys na položaju koji odgovara položaju 167, 169, 170, 171, 172, 173, 174, 175, 180 ili položaju 181 u zrelom ljudskom FGF21 (SEQ ID NO:1)
gdje navedeni derivat sadrži transporter vezan na navedeni ostatak Cys spojnicom;
gdje se transporter bira iz skupine koju čine
Chem. 1A: HOOC-(CH2)x-CO-*,
Chem. 1B: HOOC-benzen-O-(CH2)x-CO-*
i
Chem. 1C: HO-S(=O)2-(CH2)x-CO-*
gdje je x cijeli broj u rasponu od 8-18; i
gdje spojnica sadrži najmanje jedan od svakog od Chem. 2, Chem. 3 i Chem. 4:
gdje se Chem. 2 bira između:
*-NH-CH(COOH)-(CH2)m-CO-*,
*-NH-S(=O)2-(CH2)m-CO-*
i
*-NH-(CH2)m-cikloheksan-CO-*,
gdje je m cijeli broj u rasponu od 1-5,
gdje je Chem. 3 *-NH-(CH2)2-[O-(CH2)2]k-O-[CH2]n-CO-*, gdje je k cijeli broj u rasponu od 1-5, a n je cijeli broj u rasponu od 1-5, i
gdje se Chem. 4 bira između
*-NH-(CH2)m-NH-CO-CH2-*
i
*-NH-CH(COOH)-(CH2)m-NH-CO-CH2-*
gdje je m cijeli broj u rasponu od 1-5; i
gdje Chem. 2, Chem. 3, i Chem. 4 su međusobno spojeni amidnim vezama i u naznačenom slijedu, spojenom na svom *-NH kraju s CO-* krajem transportera, a na svom CH2-* kraju s atomom sumpora u ostatku Cys na položaju koji odgovara položaju 167, 169, 170, 171, 172, 173, 174, 175, 180 ili položaj 181 u zrelom ljudskom FGF21 (SEQ ID NO:1), ili njegova farmaceutski prihvatljiva sol, amid ili ester.
2. Derivat u skladu s patentnim zahtjevom 1, naznačen time što se Chem. 1 bira iz skupine koju čine:
Chem. 1a: HOOC-(CH2)16-CO-*,
Chem. 1b: HOOC-benzen-O-(CH2)9-CO-*
i
Chem. 1c: HO-S(=O)2-(CH2)15-CO-*.
3. Derivat u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačen time što se Chem. 2 bira iz skupine koju čine:
Chem. 2a: *-NH-CH(COOH)-(CH2)2-CO-*,
Chem. 2b: *-NH-S(=O)2-(CH2)3-CO-*
i
Chem. 2c: *-NH-CH2-cikloheksan-CO-*.
4. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se Chem. 4 bira između:
Chem. 4a: *-NH-(CH2)2-NH-CO-CH2-*
i
Chem. 4b: *-NH-CH(COOH)-(CH2)4-NH-CO-CH2-*.
5. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što navedeni protein sadrži ostatak Cys na položaju koji odgovara položaju 167, 170, 171, 172, 173, 174, 175, 180 ili 181 zrelog ljudskog FGF21 (SEQ ID NO:1), poput 180 zrelog ljudskog FGF21.
6. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što navedeni protein sadrži ostatak Cys na položaju koji odgovara položaju 180 ili 181 u zrelom ljudskom FGF21 (SEQ ID NO:1).
7. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što protein sadrži promjene aminokiselina na jednom ili više položaja, koji odgovaraju jednom ili više položaja 121 ili 168 u zrelom ljudskom FGF21 (SEQ ID NO:1).
8. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što protein sadrži aditciju ostatka Ala na položaju koji odgovara N-kraju zrelog ljudskog FGF21 (SEQ ID NO:1).
9. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što protein sadrži jedan ili više 121Q i 168L, poput 121Q ili 168L ili oba.
10. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što protein ima aminokiselinski slijed SEQ ID NO: 8, 10, 12, 15, 16, 17, 18, 19 ili 20.
11. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što protein sadrži aminokiselinski slijed SEQ ID NO: 8 ili 10.
12. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što transporter sadrži Chem. 1a: HOOC-(CH2)16-CO-*.
13. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što spojnica sadrži jedan, dva ili tri od sljedećeg:
Chem. 2a: *-NH-CH(COOH)-(CH2)2-CO-*,
Chem. 3a: *-NH-(CH2)2-O-(CH2)2-O-CH2-CO-*
i
Chem. 4a: *-NH-(CH2)2-NH-CO-CH2-*.
14. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što se spojnica sastoji od jednog elementa Chem. 2, dva elementa Chem. 3 i jednog elementa Chem. 4.
15. Derivat u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je derivat jedan od sljedećih:
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(11-karboksiundekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 13)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(13-karboksitridekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 14)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(15-karboksipentadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 15)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 16)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(19-karboksinonadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 17)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180,des181]FGF21 (Spoj 18)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(11-karboksiundekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 19)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(13-karboksitridekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 20)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(15-karboksipentadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 21)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 22)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(19-karboksinonadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 23)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Met[Cys181]FGF21 (Spoj 24)
;
S{Beta-169}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(15-karboksipentadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys169]FGF21 (Spoj 35)
;
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-(2-acetamidoetilamino)-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-18-oksooktadekanska kiselina-Ala[Gln121,Leu168,Cys170]FGF21 (Spoj 36)
;
S{Beta-173}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(15-karboksipentadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys173]FGF21 (Spoj 37)
;
S{Beta-174}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(13-karboksitridekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys174]FGF21 (Spoj 38)
;
18-[[(1S)-4-[2-[2-[2-[2-[2-[2-(2-acetamidoetilamino)-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-18-oksooktadekanska kiselina-Ala[Gln121,Leu168,Cys174]FGF21 (Spoj 39)
;
16-[[(1S)-4-[2-[2-[2-[2-[2-[2-(2-acetamidoetilamino)-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-16-oksoheksadekanska kiselina-Ala[Gln121,Leu168,Cys174]FGF21 (Spoj 40)
;
S{Beta-175}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(15-karboksipentadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys175]FGF21 (Spoj 41)
;
4-[10-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-10-oksodekoksi]benzojeva kiselina]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 43)
;
4-[10-[[4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-4-oksobutil]sulfonilamino]-10-oksodekoksi]benzojeva kiselina]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 44)
;
20-[[(1S)-4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-1-karboksi-4-oksobutil]amino]-20-oksoikozanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 45)
;
20-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-20-oksoikozanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 46)
;
(2S)-6-acetamido-2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(16-sulfoheksadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amin o]heksadekanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 47)
;
12-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-12-oksododekanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 48)
;
12-[[(1S)-4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-1-karboksi-4-oksobutil]amino]-12-oksododekanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 49)
;
20-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-[(2-acetamido]-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]karbamoil]cikloheksil]metilamino]-20-oksoikozanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 50)
;
16-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-(2-acetamidoetilamino)-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]karbamoil]cikloheksil]metilamino]-16-oksoheksadekanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 51)
;
16-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-[(2-acetamido]-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]karbamoil]cikloheksil]metilamino]-16-oksoheksadekanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 52)
;
18-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-[(2-acetamido]-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]karbamoil]cikloheksil]metilamino]-18-oksooktadekanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 53)
;
12-[[4-[[(1S)-4-[2-[2-[2-[2-[2-[2-(2-acetamidoetilamino)-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]karbamoil]cikloheksil]metilamino]-12-oksododekanska kiselina-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 54)
;
4-[10-[[(1S)-4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-1-karboksi-4-oksobutil]amino]-10-oksodekoksi]benzojeva kiselina]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 55)
;
4-[10-[[4-[2-[2-[2-[2-[2-[2-[[(1S)-5-acetamido-1-karboksipentil]amino]-2-oksoetoksi]etoksi]etilamino]-2-oksoetoksi]etoksi]etilamino]-4-oksobutil]sulfonilamino]-10-oksodekoksi]benzojeva kiselina-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 56)
.
16. Derivat proteina FGF21, naznačen time što je navedeni derivat jedan od sljedećih:
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(11-karboksiundekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 13)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(13-karboksitridekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 14)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(15-karboksipentadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 15)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 16)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(19-karboksinonadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180]FGF21 (Spoj 17)
;
S{Beta-180}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys180,des181]FGF21 (Spoj 18)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(11-karboksiundekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 19)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(13-karboksitridekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 20)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(15-karboksipentadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 21)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 22)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(19-karboksinonadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Ala[Gln121,Leu168,Cys181]FGF21 (Spoj 23)
;
S{Beta-181}-[2-[2-[[2-[2-[2-[[2-[2-[2-[[(4S)-4-karboksi-4-(17-karboksiheptadekanoilamino)butanoil]amino]etoksi]etoksi]acetil]amino]etoksi]etoksi]acetil]amino]etilamino]-2-oksoetil]-Met[Cys181]FGF21 (Spoj 24)
.
17. Derivat u skladu s bilo kojim od patentnih zahtjeva 1-16, naznačen time što je namijenjen upotrebi kao medikament.
18. Derivat u skladu s bilo kojim od patentnih zahtjeva 1-16, naznačen time što je namijenjen upotrebi u postupku liječenja i/ili sprječavanja bilo kojih od svih oblika dijabetesa i srodnih bolesti, poput pretilosti, poremećaja uzimanja hrane, kardiovaskularnih bolesti, komplikacija dijabetesa; i/ili poboljšavanja parametara lipida, poboljšavanja funkcije β-stanica; i/ili odgađanju ili sprječavanju napredovanja dijabetične bolesti; i/ili liječenju i/ili sprječavanju steatoze jetre i nealkoholne bolesti masne jetre (NAFLD).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP14199935 | 2014-12-23 | ||
| PCT/EP2015/080969 WO2016102562A1 (en) | 2014-12-23 | 2015-12-22 | Fgf21 derivatives and uses thereof |
| EP15817847.5A EP3236991B1 (en) | 2014-12-23 | 2015-12-22 | Fgf21 derivatives and uses thereof |
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| Publication Number | Publication Date |
|---|---|
| HRP20191292T1 true HRP20191292T1 (hr) | 2019-10-18 |
Family
ID=52130150
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20191292TT HRP20191292T1 (hr) | 2014-12-23 | 2019-07-17 | Derivati fgf21 i njihova upotreba |
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| Country | Link |
|---|---|
| US (3) | US9744213B2 (hr) |
| EP (1) | EP3236991B1 (hr) |
| JP (1) | JP6727210B2 (hr) |
| KR (1) | KR102427527B1 (hr) |
| CN (1) | CN107108709B (hr) |
| AR (1) | AR103246A1 (hr) |
| AU (1) | AU2015371056B2 (hr) |
| BR (1) | BR112017011552A2 (hr) |
| CA (1) | CA2972128A1 (hr) |
| DK (1) | DK3236991T3 (hr) |
| ES (1) | ES2742503T3 (hr) |
| HK (1) | HK1246156B (hr) |
| HR (1) | HRP20191292T1 (hr) |
| HU (1) | HUE044783T2 (hr) |
| IL (1) | IL252438B (hr) |
| MX (1) | MX2017007458A (hr) |
| MY (1) | MY181181A (hr) |
| PL (1) | PL3236991T3 (hr) |
| PT (1) | PT3236991T (hr) |
| RS (1) | RS59154B1 (hr) |
| RU (1) | RU2729011C2 (hr) |
| SA (1) | SA517381673B1 (hr) |
| SI (1) | SI3236991T1 (hr) |
| TW (2) | TWI681966B (hr) |
| WO (1) | WO2016102562A1 (hr) |
| ZA (1) | ZA201703768B (hr) |
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| CN106421753A (zh) * | 2016-10-19 | 2017-02-22 | 哈尔滨医科大学 | 重组人成纤维细胞生长因子‑21在制备预防和治疗缺血性心律失常药物中的应用 |
| TWI710377B (zh) | 2017-05-23 | 2020-11-21 | 丹麥商諾佛 儂迪克股份有限公司 | Ｍｉｃ－１化合物及其用途 |
| JP6852939B2 (ja) * | 2017-09-04 | 2021-03-31 | ８９バイオ リミテッド８９Ｂｉｏ Ｌｔｄ． | 変異体ｆｇｆ−２１ペプチドコンジュゲート及びその使用 |
| EP3817720A2 (en) | 2018-07-03 | 2021-05-12 | Bristol-Myers Squibb Company | Fgf21 formulations |
| US11427623B1 (en) | 2019-05-28 | 2022-08-30 | 89Bio Ltd. | Methods of treatment using mutant FGF-21 peptide conjugates |
| WO2021139744A1 (en) | 2020-01-11 | 2021-07-15 | Beijing Ql Biopharmaceutical Co., Ltd. | Conjugates of fusion proteins of glp-1 and fgf21 |
| EP4337680A1 (en) | 2021-05-11 | 2024-03-20 | Cytoki Pharma ApS | Therapeutic derivatives of interleukin-22 |
| EP4089108A1 (en) | 2021-05-11 | 2022-11-16 | CytoKi Pharma ApS | Therapeutic derivatives of interleukin-22 |
| KR102631925B1 (ko) * | 2021-06-10 | 2024-02-01 | 토드제약 주식회사 | 신규 fgf21 변이체 개발 및 이의 생산기법과 용도 |
| WO2024008904A2 (en) | 2022-07-08 | 2024-01-11 | Novo Nordisk A/S | Highly potent isvd compounds capable of substituting for fviii(a) |
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| US20040259780A1 (en) | 2001-07-30 | 2004-12-23 | Glasebrook Andrew Lawrence | Method for treating diabetes and obesity |
| EP1329227A1 (en) | 2002-01-22 | 2003-07-23 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Diagnostic conjugate useful for intercellular imaging and for differentiating between tumor- and non-tumor cells |
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| TW200522976A (en) | 2003-09-19 | 2005-07-16 | Novo Nordisk As | Novel plasma protein affinity tags |
| CA2539253A1 (en) | 2003-09-19 | 2005-03-31 | Novo Nordisk A/S | Albumin-binding derivatives of therapeutic peptides |
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-
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