HRP20191052T1 - Predlijek koji obuhvaća samocijepajuću poveznicu - Google Patents
Predlijek koji obuhvaća samocijepajuću poveznicu Download PDFInfo
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- HRP20191052T1 HRP20191052T1 HRP20191052T HRP20191052T1 HR P20191052 T1 HRP20191052 T1 HR P20191052T1 HR P20191052 T HRP20191052 T HR P20191052T HR P20191052 T1 HRP20191052 T1 HR P20191052T1
- Authority
- HR
- Croatia
- Prior art keywords
- group
- alkyl
- poly
- prodrug according
- membered
- Prior art date
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- 229940002612 prodrug Drugs 0.000 title claims 31
- 239000000651 prodrug Substances 0.000 title claims 31
- -1 bifalin Chemical compound 0.000 claims 35
- 125000000217 alkyl group Chemical group 0.000 claims 17
- 125000003342 alkenyl group Chemical group 0.000 claims 12
- 125000000304 alkynyl group Chemical group 0.000 claims 12
- 125000000623 heterocyclic group Chemical group 0.000 claims 8
- 102000004169 proteins and genes Human genes 0.000 claims 8
- 108090000623 proteins and genes Proteins 0.000 claims 8
- 229910052736 halogen Inorganic materials 0.000 claims 7
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 4
- 239000003814 drug Substances 0.000 claims 4
- 239000012634 fragment Substances 0.000 claims 4
- 125000005843 halogen group Chemical group 0.000 claims 4
- 108090000765 processed proteins & peptides Proteins 0.000 claims 4
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 3
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims 3
- 108020001621 Natriuretic Peptide Proteins 0.000 claims 3
- 102000004571 Natriuretic peptide Human genes 0.000 claims 3
- 239000012867 bioactive agent Substances 0.000 claims 3
- 239000003795 chemical substances by application Substances 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 150000002367 halogens Chemical class 0.000 claims 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims 3
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims 3
- 125000001624 naphthyl group Chemical group 0.000 claims 3
- 239000000692 natriuretic peptide Substances 0.000 claims 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 3
- 229920001184 polypeptide Polymers 0.000 claims 3
- 102000004196 processed proteins & peptides Human genes 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 150000003384 small molecules Chemical class 0.000 claims 3
- 239000000126 substance Substances 0.000 claims 3
- 125000001424 substituent group Chemical group 0.000 claims 3
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 claims 3
- 229960005486 vaccine Drugs 0.000 claims 3
- 108010039627 Aprotinin Proteins 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims 2
- 229940089838 Glucagon-like peptide 1 receptor agonist Drugs 0.000 claims 2
- RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 claims 2
- 108060003951 Immunoglobulin Proteins 0.000 claims 2
- 102000014150 Interferons Human genes 0.000 claims 2
- 108010050904 Interferons Proteins 0.000 claims 2
- 102000015696 Interleukins Human genes 0.000 claims 2
- 108010063738 Interleukins Proteins 0.000 claims 2
- XUIIKFGFIJCVMT-LBPRGKRZSA-N L-thyroxine Chemical compound IC1=CC(C[C@H]([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-LBPRGKRZSA-N 0.000 claims 2
- 239000004365 Protease Substances 0.000 claims 2
- 101100212791 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) YBL068W-A gene Proteins 0.000 claims 2
- 229920002472 Starch Polymers 0.000 claims 2
- 102000011923 Thyrotropin Human genes 0.000 claims 2
- 108010061174 Thyrotropin Proteins 0.000 claims 2
- 102000015395 alpha 1-Antitrypsin Human genes 0.000 claims 2
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 claims 2
- 125000004429 atom Chemical group 0.000 claims 2
- BLFLLBZGZJTVJG-UHFFFAOYSA-N benzocaine Chemical compound CCOC(=O)C1=CC=C(N)C=C1 BLFLLBZGZJTVJG-UHFFFAOYSA-N 0.000 claims 2
- 229920001222 biopolymer Polymers 0.000 claims 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims 2
- WHBIGIKBNXZKFE-UHFFFAOYSA-N delavirdine Chemical compound CC(C)NC1=CC=CN=C1N1CCN(C(=O)C=2NC3=CC=C(NS(C)(=O)=O)C=C3C=2)CC1 WHBIGIKBNXZKFE-UHFFFAOYSA-N 0.000 claims 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims 2
- AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Chemical compound CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 claims 2
- 108020001507 fusion proteins Proteins 0.000 claims 2
- 102000037865 fusion proteins Human genes 0.000 claims 2
- BGHSOEHUOOAYMY-JTZMCQEISA-N ghrelin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)CN)C1=CC=CC=C1 BGHSOEHUOOAYMY-JTZMCQEISA-N 0.000 claims 2
- 239000003877 glucagon like peptide 1 receptor agonist Substances 0.000 claims 2
- 239000000017 hydrogel Substances 0.000 claims 2
- 102000018358 immunoglobulin Human genes 0.000 claims 2
- 229940047124 interferons Drugs 0.000 claims 2
- 229940047122 interleukins Drugs 0.000 claims 2
- 229950008325 levothyroxine Drugs 0.000 claims 2
- RHCSKNNOAZULRK-UHFFFAOYSA-N mescaline Chemical compound COC1=CC(CCN)=CC(OC)=C1OC RHCSKNNOAZULRK-UHFFFAOYSA-N 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 210000002381 plasma Anatomy 0.000 claims 2
- 229920001223 polyethylene glycol Polymers 0.000 claims 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims 2
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 claims 2
- 229960002073 sertraline Drugs 0.000 claims 2
- 239000008107 starch Substances 0.000 claims 2
- 235000019698 starch Nutrition 0.000 claims 2
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 claims 2
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims 1
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 claims 1
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims 1
- HMJIYCCIJYRONP-UHFFFAOYSA-N (+-)-Isradipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)C1C1=CC=CC2=NON=C12 HMJIYCCIJYRONP-UHFFFAOYSA-N 0.000 claims 1
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims 1
- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 claims 1
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims 1
- GJJFMKBJSRMPLA-HIFRSBDPSA-N (1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenyl-1-cyclopropanecarboxamide Chemical compound C=1C=CC=CC=1[C@@]1(C(=O)N(CC)CC)C[C@@H]1CN GJJFMKBJSRMPLA-HIFRSBDPSA-N 0.000 claims 1
- IGLYMJRIWWIQQE-QUOODJBBSA-N (1S,2R)-2-phenylcyclopropan-1-amine (1R,2S)-2-phenylcyclopropan-1-amine Chemical compound N[C@H]1C[C@@H]1C1=CC=CC=C1.N[C@@H]1C[C@H]1C1=CC=CC=C1 IGLYMJRIWWIQQE-QUOODJBBSA-N 0.000 claims 1
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 claims 1
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 claims 1
- YWPHCCPCQOJSGZ-LLVKDONJSA-N (2r)-2-[(2-ethoxyphenoxy)methyl]morpholine Chemical compound CCOC1=CC=CC=C1OC[C@@H]1OCCNC1 YWPHCCPCQOJSGZ-LLVKDONJSA-N 0.000 claims 1
- BUJAGSGYPOAWEI-SECBINFHSA-N (2r)-2-amino-n-(2,6-dimethylphenyl)propanamide Chemical compound C[C@@H](N)C(=O)NC1=C(C)C=CC=C1C BUJAGSGYPOAWEI-SECBINFHSA-N 0.000 claims 1
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 claims 1
- OOBHFESNSZDWIU-GXSJLCMTSA-N (2s,3s)-3-methyl-2-phenylmorpholine Chemical compound C[C@@H]1NCCO[C@H]1C1=CC=CC=C1 OOBHFESNSZDWIU-GXSJLCMTSA-N 0.000 claims 1
- DDYAPMZTJAYBOF-ZMYDTDHYSA-N (3S)-4-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3R)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(1S)-1-carboxyethyl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,3R)-2-[[2-[[(2S)-5-amino-2-[[(2S)-2-[[(2S)-2-amino-3-(1H-imidazol-4-yl)propanoyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]acetyl]amino]-3-hydroxybutanoyl]amino]-3-phenylpropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxypropanoyl]amino]-3-carboxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-3-hydroxypropanoyl]amino]hexanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-methylpentanoyl]amino]-3-carboxypropanoyl]amino]-3-hydroxypropanoyl]amino]-5-carbamimidamidopentanoyl]amino]-5-carbamimidamidopentanoyl]amino]propanoyl]amino]-5-oxopentanoyl]amino]-4-oxobutanoic acid Chemical class [H]N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC1=CC=C(O)C=C1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC1=CC=CC=C1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC1=CNC2=C1C=CC=C2)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O DDYAPMZTJAYBOF-ZMYDTDHYSA-N 0.000 claims 1
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 claims 1
- VQHRZZISQVWPLK-UIRGBLDSSA-N (7s,9s)-7-[(2r,4s,5s,6s)-5-[(2s,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-4-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@H]1[C@@H](O)C[C@H](O[C@@H]2C3=C(O)C=4C(=O)C5=CC=CC=C5C(=O)C=4C(O)=C3C[C@](O)(C2)C(=O)CO)O[C@H]1C VQHRZZISQVWPLK-UIRGBLDSSA-N 0.000 claims 1
- 125000003837 (C1-C20) alkyl group Chemical group 0.000 claims 1
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 claims 1
- 229930182837 (R)-adrenaline Natural products 0.000 claims 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 claims 1
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims 1
- ZEUITGRIYCTCEM-KRWDZBQOSA-N (S)-duloxetine Chemical compound C1([C@@H](OC=2C3=CC=CC=C3C=CC=2)CCNC)=CC=CS1 ZEUITGRIYCTCEM-KRWDZBQOSA-N 0.000 claims 1
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 claims 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 claims 1
- ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 claims 1
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- 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 (35)
1. Predlijek ili njegova farmaceutski prihvatljiva sol od lijeka D-H, naznačen time, da se predlijek ili njegova farmaceutski prihvatljiva sol sastoje od konjugata lijek-poveznica D-L (engl. drug-linker), pri čemu
- D je biološki aktivni dio skupine lijeka D-H koji sadrži dušik; i
- L ne pokazuje farmakološke učinke lijeka D-H i predstavlja dio skupine –L1-(L2-Z)1-4, gdje je
- L1 predstavljen s formulom (I),
u kojoj crtkana linija označava priključak na dušik od biološki aktivnog dijela skupine kroz formaciju amidne veze;
X je C(R4R4a); N(R4); O; C(R4R4a)-C(R5R5a); C(R5R5a)-C(R4R4a);
C(R4R4a)-N(R6); N(R6)-C(R4R4a); C(R4R4a)-O; ili O-C(R4R4a);
X1 je C; ili S(O);
X2 je C(R7, R7a); ili C(R7, R7a)-C(R8, R8a);
X3 je O;
R1, R1a, R2, R2a, R3, R3a, R4, R4a, R5, R5a, R6, R7, R7a, R8, R8a su neovisno odabrani iz skupine koja se sastoji od H; i C1-4alkila;
alternativno, jedan ili više od parova R1a/R4a, R1a/R5a, R4a/R5a, R7a/R8a, tvore kemijsku vezu;
alternativno, jedan ili više od parova R1/R1a, R2/R2a, R4/R4a, R5/R5a, R7/R7a, R8/R8a, sjedinjeni su zajedno s atomom na kojega su priključeni, kako bi tvorili
C3-7 cikloalkil; ili 4-člani do 7-člani heterociklil;
alternativno, jedan ili više od parova R1/R4, R1/R5, R1/R6, R4/R5, R4/R6, R7/R8, R2/R3, sjedinjeni su zajedno s atomima na koje su priključeni, kako bi tvorili prsten A;
alternativno, R3/R3a su sjedinjeni zajedno s atomom dušika na kojega su priključeni, kako bi tvorili 4-člani do 7-člani heterocikl;
A je odabran iz skupine koja se sastoji od sljedećih: fenil; naftil; indenil; indanil; tetralinil; C3-10 cikloalkil; 4-člani do 7-člani heterociklil; i 9-člani do 11-člani heterobiciklil; i
pritom je L1 opcionalno dalje supstituiran,
gdje su jedan ili više daljnjih opcionalnih supstituenata neovisno odabrani iz skupine koja se sastoji od sljedećih: halogen; CN; COOR9; OR9; C(O)R9;
C(O)N(R9R9a); S(O)2N(R9R9a); S(O)N(R9R9a); S(O)2R9; S(O)R9; N(R9)S(O)2N(R9aR9b); SR9; N(R9R9a); NO2; OC(O)R9; N(R9)C(O)R9a;
N(R9)S(O)2R9a; N(R9)S(O)R9a; N(R9)C(O)OR9a; N(R9)C(O)N(R9aR9b);
OC(O)N(R9R9a); T; C1-50 alkil; C2-50 alkenil; i C2-50 alkinil,
pri čemu su T; C1-50 alkil; C2-50 alkenil; i C2-50 alkinil, opcionalno supstituirani s jednim ili više R10, koji su isti ili različiti i pritom su C1-50 alkil; C2-50 alkenil; i C2-50 alkinil opcionalno prekinuti s jednom ili više skupina odabranih iz skupine koju čine sljedeći: T; -C(O)O-; -O-; -C(O)-; -C(O)N(R11)-; -S(O)2N(R11)-;
-S(O)N(R11)-; -S(O)2-; -S(O)-; -N(R11)S(O)2N(R11a)-; -S-; -N(R11)-; -OC(O)R11;
-N(R11)C(O)-; -N(R11)S(O)2-; -N(R11)S(O)-; -N(R11)C(O)O-;
-N(R11)C(O)N(R11a); i –OC(O)N(R11R11a), gdje su
R9, R9a, R9b neovisno odabrani iz skupine koja se sastoji od sljedećih: H; T;
C1-50 alkil; C2-50 alkenil; i C2-50 alkinil, pri čemu su T; C1-50 alkil; C2-50 alkenil; i C2-50 alkinil, opcionalno supstituirani s jednim ili više R10, koji su isti ili različiti i pritom su C1-50 alkil; C2-50 alkenil; i C2-50 alkinil opcionalno prekinuti s jednom ili više skupina odabranih iz skupine koju čine sljedeći: T; -C(O)O-; -O-; -C(O)-; -C(O)N(R11)-; -S(O)2N(R11)-; -S(O)N(R11)-; -S(O)2-; -S(O)-;
-N(R11)S(O)2N(R11a)-; -S-; -N(R11)-; -OC(O)R11; -N(R11)C(O)-; -N(R11)S(O)2-;
-N(R11)S(O)-; -N(R11)C(O)O-; -N(R11)C(O)N(R11a)-; i –OC(O)N(R11R11a);
T je fenil; naftil; indenil; indanil; tetralinil; C3-10 cikloalkil; 4-člani do 7-člani heterociklil; ili 9-člani do 11-člani heterobiciklil; dok je T opcionalno supstituiran s jednim ili više R10 koji su isti ili različiti;
R10 je halogen; CN; okso (=O); COOR12; OR12; C(O)R12;
C(O)N(R12R12a); S(O)2N(R12R12a); S(O)N(R12R12a); S(O)2R12; S(O)R12; N(R12)S(O)2N(R12aR12b); SR12; N(R12R12a); NO2; OC(O)R12; N(R12)C(O)R12a;
N(R12)S(O)2R12a; N(R12)S(O)R12a; N(R12)C(O)OR12a; N(R12)C(O)N(R12aR12b);
OC(O)N(R12R12a); ili C1-6 alkil, gdje je C1-6 alkil opcionalno supstituiran s jednim ili više halogena koji su isti ili različiti;
R11, R11a, R12, R12a, R12b su neovisno odabrani iz skupine koja se sastoji od H; i C1-6 alkila, gdje je C1-6 alkil opcionalno supstituiran s jednim ili više halogena
koji su isti ili različiti;
uz uvjet da vodik koji je označen sa zvjezdicom u formuli (I) nije zamijenjen s L2-Z ili supstituentom od jednog ili više dodatnih supstituenata;
L2 je jednostruka kemijska veza ili držač razmaka; i
Z je nosiva skupina, pri čemu je ta nosiva skupina polimer od najmanje 500 Da ili C8-18 alkil-skupina.
2. Predlijek prema zahtjevu 1, naznačen time, da X je N(R4) i X1 je C.
3. Predlijek prema zahtjevu 1 ili 2, naznačen time, da X2 je C(R7R7a).
4. Predlijek prema zahtjevu 1, naznačen time, da L1 je odabran iz skupine koju čine:
pri čemu R je H; ili C1-4 alkil; Y je NH; O; ili S; i
R1, R1a, R2, R2a, R3, R3a, R4, X, X1, X2 imaju značenje kao što je naznačeno u zahtjevu 1.
5. Predlijek prema zahtjevu 1, naznačen time, da L1 je odabran iz skupine koju čine:
gdje R je H; ili C1-4 alkil.
6. Predlijek prema bilo kojem od zahtjeva 1 do 5, naznačen time, da L2 je jednostruka kemijska veza.
7. Predlijek prema bilo kojem od zahtjeva 1 do 5, naznačen time, da L2-Z je COOR9'; OR9'; C(O)R9'; C(O)N(R9'R9a'); S(O)2N(R9'R9a'); S(O)N(R9'R9a'); S(O)2R9'; S(O)R9'; N(R9')S(O)2N(R9a'R9b'); SR9'; N(R9'R9a'); OC(O)R9'; N(R9')C(O)R9a'; N(R9')S(O)2R9a'; N(R9')S(O)R9a'; N(R9')C(O)OR9a'; N(R9')C(O)N(R9'aR9b'); OC(O)N(R9'R9a'); T; C1-50 alkil; C2-50 alkenil; ili
C2-50 alkinil, gdje su T; C1-50 alkil; C2-50 alkenil; i C2-50 alkinil opcionalno supstituirani s jednim ili više R10 koji su isti ili različiti i pritom su C1-50 alkil;
C2-50 alkenil; i C2-50 alkinil opcionalno prekinuti s jednom ili više skupina odabranih iz skupine koja se sastoji od sljedećih: -T-; -C(O)O-; -O-; -C(O)-;
-C(O)N(R11')-; -S(O)2N(R11')-; -S(O)N(R11')-; -S(O)2-; -S(O)-;
-N(R11')S(O)2N(R11a')-; -S-; -N(R11')-; -OC(O)R11'; -N(R11')C(O)-;
-N(R11')S(O)2-; -N(R11')S(O)-; -N(R11')C(O)O-; -N(R11')C(O)N(R11a'); i
–OC(O)N(R11'R11a');
R9', R9a', R9b' su neovisno odabrani iz skupine koja se sastoji od sljedećih: H; Z; T;
C1-50 alkil; C2-50 alkenil; i C2-50 alkinil, pri čemu su T; C1-50 alkil; C2-50 alkenil; i C2-50 alkinil, opcionalno supstituirani s jednim ili više R10, koji su isti ili različiti i pritom su C1-50 alkil; C2-50 alkenil; i C2-50 alkinil opcionalno prekinuti s jednom ili više skupina odabranih iz skupine koju čine sljedeći: T; -C(O)O-; -O-; -C(O)-; -C(O)N(R11')-; -S(O)2N(R11')-; -S(O)N(R11')-; -S(O)2-; -S(O)-;
-N(R11')S(O)2N(R11a')-; -S-; -N(R11')-; -OC(O)R11'; -N(R11')C(O)-; -N(R11')S(O)2-;
-N(R11')S(O)-; -N(R11')C(O)O-; -N(R11')C(O)N(R11a'); i –OC(O)N(R11'R11a');
T je fenil; naftil; indenil; indanil; tetralinil; C3-10 cikloalkil; 4-člani do 7-člani heterociklil; ili 9-člani do 11-člani heterobiciklil; dok je T opcionalno supstituiran s jednim ili više R10' koji su isti ili različiti;
R10' je halogen; CN; okso (=O); COOR12'; OR12'; C(O)R12';
C(O)N(R12'R12a'); S(O)2N(R12'R12a'); S(O)N(R12'R12a'); S(O)2R12'; S(O)R12'; N(R12')S(O)2N(R12a'R12b'); SR12'; N(R12'R12a'); NO2; OC(O)R12'; N(R12')C(O)R12a';
N(R12')S(O)2R12a'; N(R12')S(O)R12a'; N(R12')C(O)OR12a'; N(R12')C(O)N(R12a'R12b');
OC(O)N(R12'R12a'); ili C1-6 alkil, gdje je C1-6 alkil opcionalno supstituiran s jednim ili više halogena koji su isti ili različiti;
R11', R11a', R12', R12a', R12b' su neovisno odabrani iz skupine koja se sastoji od H; Z; i C1-6 alkila, gdje je C1-6 alkil opcionalno supstituiran s jednim ili više halogena koji su isti ili različiti;
uz uvjet da jedan od R9', R9a', R9b', R10', R11', R11a', R12', R12a', R12b' je Z.
8. Predlijek prema bilo kojem od zahtjeva 1 do 5 ili 7, naznačen time, da L2 je
C1-20 alkil-lanac koji je opcionalno prekinut s jednom ili više skupina neovisno odabranih od –O-; i C(O)N(R3aa); opcionalno supstituiran s jednom ili više skupina neovisno odabranih od OH; i C(O)N(R3aaR3aaa); i pri čemu su R3aa, R3aaaneovisno odabrani iz skupine koju čine H; i C1-4 alkil.
9. Predlijek prema bilo kojem od zahtjeva 1 do 5, 7 ili 8, naznačen time, da L2 ima molekularnu masu u rasponu od 14 g/mol do 750 g/mol.
10. Predlijek prema bilo kojem od zahtjeva 1 do 5 ili 7 do 9, naznačen time, da L2 je priključen na Z putem terminalne skupine odabrane od sljedećih:
11. Predlijek prema bilo kojem od zahtjeva 1 do 10, naznačen time, da L je predstavljen formulom (Ia):
u kojoj
R4, L2 i Z imaju značenje koje je naznačeno u zahtjevu 1, i pritom su R3aa, R3aaa neovisno odabrani iz skupine koja se sastoji od H; i C1-4 alkila; ili su
sjedinjeni zajedno s atomom dušika na kojega su priključeni, u svrhu tvorbe 4-članog do 7-članog heterocikla.
12. Predlijek prema bilo kojem od zahtjeva 1 do 10, naznačen time, da L je predstavljen formulom (Ib):
u kojoj
R1, R1a, R4, L2 i Z imaju značenje koje je naznačeno u zahtjevu 1, i pritom R3aa je H; ili C1-4 alkil.
13. Predlijek prema bilo kojem od zahtjeva 1 do 10, naznačen time, da R1 u formuli (I) je L2-Z.
14. Predlijek prema bilo kojem od zahtjeva 1 do 10, naznačen time, da R3 u formuli (I) je L2-Z.
15. Predlijek prema bilo kojem od zahtjeva 1 do 10, naznačen time, da su R3, R3a u formuli (I) sjedinjeni zajedno s atomom dušika na kojega su priključeni, u svrhu tvorbe 4-članog do 7-članog heterocikla i pritom je heterocikl supstituiran s L2-Z.
16. Predlijek prema bilo kojem od zahtjeva 1 do 15, naznačen time, da D-H je bioaktivno sredstvo male molekule ili biopolimer.
17. Predlijek prema bilo kojem od zahtjeva 1 do 16, naznačen time, da D-H je biopolimer odabran iz skupine koja se sastoji od proteina, polipeptida, oligonukleotida i peptidnih nukleinskih kiselina.
18. Predlijek prema bilo kojem od zahtjeva 1 do 17, naznačen time, da D-H je polipeptid odabran iz skupine polipeptida koja se sastoji od sljedećih: ACTH, adenozin deaminaza, agalsidaza, alfa-1-antitripsin, inhibitor alfa-1-proteinaze,
alteplaza, amilin, simlin, anistreplaza, ankrod-serin-proteaza, protutijela, antitrombin III, antitripsini, aprotinin, asparaginaze, atosiban, bifalin, bivalirudin, morfogeni proteini kostiju, inhibitor tripsina gušterače goveda, fragmenti kadherina, kalcitonin iz lososa, kolagenaza, inhibitor esteraze komplementa C1, konotoksini, fragmenti citokinskih receptora, DNaza, dinorfin A, endorfini, enfuvirtid, enkefalini, eritropoietini, eksendini, faktor VII, faktor VIIa, faktor VIII, faktor VIIIa, faktor IX, fibrinolizin, fibroblastni faktor rasta, peptid 2 koji oslobađa hormon rasta, fuzijski proteini, hormoni koji stimuliraju folikl, gramicidin, grelin, desacil-grelin, faktor koji stimulira koloniju granulocita, galaktosidaza, glukagon, peptidi nalik na glukagon, glukocerebrosidaza, faktor koji stimulira koloniju granulocitnih makrofaga, ljudski proteini toplotnog šoka, protein koji aktivira fosfolipazu, horionički gonadotropin, hemoglobini, cjepiva protiv hepatitisa B, hirudin, inhibitor proteaze ljudskog serina, hijaluronidaze, iduronidaze, imunoglobulini, cjepiva protiv gripe, interleukini, antagonisti receptora IL-1, inzulini, faktori rasta nalik na inzulin, vezni protein faktora rasta nalik na inzulin, interferoni, molekule intracelularne adhezije, keratinocitni faktor rasta, ligand glikoproteina P-selektina, transformacijski faktori rasta, laktaza, leptin, leuprolid, levotiroksin, luteinizirajući hormon, lajmsko cjepivo, natriuretički peptidi, neuropeptid Y, pankrelipaza, polipeptid gušterače, papain, paratiroidni hormon, PDGF, pepsin, peptid YY, faktor acetilhidrolaze koji aktivira pločaste stanice, prolaktin, protein C, timalfazin, oktreotid, sekretin, sermorelin, topivi receptor faktora tumorske nekroze, superoksidna dismutaza, somatropini, somatoprim, somatostatin, streptokinaza, sukraza, terlipresin, fragment toksina tetanusa, tilaktaza, trombini, timozin, hormon stimulacije tiroida, tirotropin, faktor tumorske nekroze, Fc TNF-receptor-IgG, aktivator plazminogena tkiva, TSH, urodilatin, uratna oksidaza, urokinaza, cjepiva, vaskularni endotelijski faktor rasta, vazoaktivni intestinalni peptid, vazopresin, zikonotid, lektin i ricin.
19. Predlijek prema zahtjevu 18, naznačen time, da su interleukini odabrani od 1 alfa, 1 beta, 2, 3, 4, 6, 10, 11, 12, 13 i 21.
20. Predlijek prema zahtjevu 18, naznačen time, da su interferoni odabrani od alfa 2a, alfa 2b, alfa 2c, beta 1a, beta 1b, gama 1a i gama 1b.
21. Predlijek prema zahtjevu 18, naznačen time, da je natriuretički peptid odabran iz skupine koja se sastoji od ANP, BNP, CNP, i fragmenata natriuretičkih peptida.
22. Predlijek prema bilo kojem od zahtjeva 1 do 21, naznačen time, da D-H je protein koji se može proizvoditi pomoću rekombinantnih DNK tehnologija.
23. Predlijek prema bilo kojem od zahtjeva 1 do 18 ili 22, naznačen time, da D-H je protein koji je odabran iz skupine proteina koja se sastoji od fragmenata protutijela, proteina koji vežu antigene jednostrukog lanca, katalitičkih protutijela i fuzijskih proteina.
24. Predlijek prema bilo kojem od zahtjeva 1 do 16, naznačen time, da D-H je bioaktivni agens male molekule odabran iz skupine sredstava koja se sastoji od aktivnih sredstava centralnog nervnog sustava, antiinfekcijskih sredstava, antialergijskih sredstava, imunomodulirajućih sredstava, sredstava protiv pretilosti, antikoagulanata, antidijabetika, antineoplastičnih sredstava, antibakterijskih sredstava, protugljivičnih sredstava, analgetika, kontraceptika, protuupalnih sredstava, steroidnih sredstava, vazodilatornih sredstava, vazokonstriktivnih sredstava i kardiovaskularnih sredstava s najmanje jednom primarnom ili sekundarnom amino skupinom.
25. Predlijek prema bilo kojem od zahtjeva 1 do 16 i 24, naznačen time, da D-H je bioaktivni agens male molekule odabran iz skupine sredstava koja se sastoji od sljedećih: akarboza, alaproklat, alendronat, amantadin, amikacin, amineptin, aminoglutetimid, amisulprid, amlodipin, amotosalen, amoksapin, amoksicilin, amfetamin, amfotericin B, ampicilin, amprenavir, amrinon, anileridin, apraklonidin, apramicin, artikain, atenolol, atomoksetin, avizafon, baklofen, benazepril, benserazid, benzokain, betaksolol, bleomicin, bromfenak, brofaromin, karvedilol, katin, katinon, karbutamid, cefaleksin, klinafloksacin, ciprofloksacin, deferoksamin, delavirdin, desipramin, daunorubicin, deksmetilfenidat,
diafenilsulfon, dizocilpin, dopamin, dobutamin, dorzolamid, doksorubicin, duloksetin, eflornitin, enalapril, epinefrin, epirubicin, ergolin, ertapenem, esmolol, enoksacin, etambutol, fenfluramin, fenoldopam, fenoterol, fingolimod, flekainid, fluvoksamin, fosamprenavir, frovatriptan, furosemid, fluoksetin, gabapentin, gatifloksacin, gemifloksacin, gentamicin, grepafloksacin, heksilkain, hidralazin, hidroklorotiazid, ikofungipen, idarubicin, imikvimod, inverzin, izoproterenol, izradipin, kanamicin A, ketamin, labetalol, lamivudin, levobunolol, levodopa, levotiroksin, lizinopril, lomefloksacin, lorakarbef, maprotilin, meflokin, melfalan, memantin, meropenem, mesalazin, meskalin, metildopa, metilendioksimetamfetamin, metoprolol, milnacipran, mitoksantron, moksifloksacin, norepinefrin, norfloksacin, nortriptilin, neomicin B, nistatin, oseltamivir, pamidronska kiselina, paroksetin, pazufloksacin, pemetreksed, perindopril, fenmetrazin, fenelzin, pregabalin, prokain, pseudoefedrin, protriptilin, reboksetin, ritodrin, sabarubicin, salbutamol, serotonin, sertralin, sitagliptin, sotalol, spektinomicin, sulfadiazin, sulfamerazin, sertralin, sulfalen, sulfametoksazol, takrin, tamsulosin, terbutalin, timolol, tirofiban, tobramicin, tokainid, tosufloksacin, trandolapril, traneksamička kiselina, tranilcipromin, trimetreksat, trovafloksacin, valaciklovir, valganciklovir, vankomicin, viomicin, viloksazin i zalcitabin.
26. Predlijek prema bilo kojem od zahtjeva 1 do 25, naznačen time, da Z je odabran iz skupine opcionalno križno povezanih polimera koja se sastoji od sljedećih: poli(propilen-glikol), poli(etilen-glikol), dekstran, kitozan, hijaluronska kiselina, alginat, ksilan, manan, karagenan, agaroza, celuloza, škrob, hidroksialkilni škrob, poli(vinil-alkoholi), poli(oksazolini), poli(anhidridi), poli(orto-esteri), poli(karbonati), poli(uretani), poli(akrilne kiseline), poli(akrilamidi), poli(akrilati), poli(metakrilati), poli(organofosfazeni), polioksazolin, poli(siloksani), poli(amidi), poli(vinilpirolidon), poli(cijanoakrilati), poli(esteri), poli(iminokarbonati), poli(aminokiseline), kolagen, želatina, hidrogel i protein krvne plazme, te njihovi kopolimeri.
27. Predlijek prema bilo kojem od zahtjeva 1 do 26, naznačen time, da Z je protein.
28. Predlijek prema bilo kojem od zahtjeva 1 do 27, naznačen time, da Z je protein odabran iz skupine koja se sastoji od albumina, transferina i imunoglobulina.
29. Predlijek prema bilo kojem od zahtjeva 1 do 25, naznačen time, da Z je ravni ili razgranati poli(etilen-glikol) s molekularnom masom od 2000 Da do 150.000 Da.
30. Predlijek prema bilo kojem od zahtjeva 1 do 29, naznačen time, da D-H je agonist receptora GLP-1; L1 je predstavljen formulom (I) kao što je naznačeno u zahtjevu 1; i Z je hidrogel.
31. Predlijek prema zahtjevu 30, naznačen time, da agonist receptora GLP-1 je eksendin-4.
32. Predlijek prema zahtjevu 30 ili 31, naznačen time, da u formuli (I), X je N(R4) i X1 je C.
33. Predlijek prema bilo kojem od zahtjeva 30 do 32, naznačen time, da L je predstavljen formulom (Ia) kao što je naznačeno u zahtjevu 11 ili je L predstavljen formulom (Ib) kao što je naznačeno u zahtjevu 12.
34. Farmaceutski sastav, naznačen time, da obuhvaća predlijek u skladu s bilo kojim od zahtjeva 1 do 33 ili njegovu farmaceutski prihvatljivu sol zajedno s farmaceutski prihvatljivim pomoćnim sredstvom.
35. Predlijek prema bilo kojem od zahtjeva 1 do 33, ili farmaceutski sastav u skladu sa zahtjevom 34, naznačen time, da se upotrebljava kao lijek.
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EP09706788.8A EP2237799B1 (en) | 2008-02-01 | 2009-01-30 | Prodrug comprising a self-cleavable linker |
PCT/EP2009/051079 WO2009095479A2 (en) | 2008-02-01 | 2009-01-30 | Prodrug comprising a self-cleavable linker |
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