EA032129B1 - Пролекарство 1,1'-(1,6-диоксо-1,6-гександиил)бис-d-пролина - Google Patents
Пролекарство 1,1'-(1,6-диоксо-1,6-гександиил)бис-d-пролина Download PDFInfo
- Publication number
- EA032129B1 EA032129B1 EA201692185A EA201692185A EA032129B1 EA 032129 B1 EA032129 B1 EA 032129B1 EA 201692185 A EA201692185 A EA 201692185A EA 201692185 A EA201692185 A EA 201692185A EA 032129 B1 EA032129 B1 EA 032129B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- compound
- disease
- formula
- present
- amyloidosis
- Prior art date
Links
- 239000000651 prodrug Substances 0.000 title description 2
- 229940002612 prodrug Drugs 0.000 title description 2
- HZLAWYIBLZNRFZ-VXGBXAGGSA-N cphpc Chemical compound OC(=O)[C@H]1CCCN1C(=O)CCCCC(=O)N1[C@@H](C(O)=O)CCC1 HZLAWYIBLZNRFZ-VXGBXAGGSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 195
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 167
- 201000010099 disease Diseases 0.000 claims abstract description 97
- 238000011282 treatment Methods 0.000 claims abstract description 91
- 108010045517 Serum Amyloid P-Component Proteins 0.000 claims abstract description 84
- 206010002022 amyloidosis Diseases 0.000 claims abstract description 81
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 76
- 208000035475 disorder Diseases 0.000 claims abstract description 70
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 36
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 31
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims abstract description 30
- 230000009286 beneficial effect Effects 0.000 claims abstract description 22
- 102100036202 Serum amyloid P-component Human genes 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 60
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 19
- 208000022256 primary systemic amyloidosis Diseases 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 16
- -1 (tetrahydro-2H-pyran-4-yl) oxy Chemical group 0.000 claims description 15
- HZLAWYIBLZNRFZ-UHFFFAOYSA-N 1-[6-(2-carboxypyrrolidin-1-yl)-6-oxohexanoyl]pyrrolidine-2-carboxylic acid Chemical compound OC(=O)C1CCCN1C(=O)CCCCC(=O)N1C(C(O)=O)CCC1 HZLAWYIBLZNRFZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 9
- 238000006460 hydrolysis reaction Methods 0.000 claims description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
- 239000002552 dosage form Substances 0.000 claims description 7
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 238000012217 deletion Methods 0.000 claims description 4
- 230000037430 deletion Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 230000008021 deposition Effects 0.000 claims description 3
- 230000002349 favourable effect Effects 0.000 claims 3
- KSKLDMGKWDUQCT-DNQXCXABSA-N oxan-4-yloxycarbonyloxymethyl (2R)-1-[6-[(2R)-2-(oxan-4-yloxycarbonyloxymethoxycarbonyl)pyrrolidin-1-yl]-6-oxohexanoyl]pyrrolidine-2-carboxylate Chemical compound C(CCCCC(=O)N1[C@H](CCC1)C(=O)OCOC(=O)OC1CCOCC1)(=O)N1[C@H](CCC1)C(=O)OCOC(=O)OC1CCOCC1 KSKLDMGKWDUQCT-DNQXCXABSA-N 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N methyl cyanide Natural products CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 38
- 239000000243 solution Substances 0.000 description 34
- 208000037259 Amyloid Plaque Diseases 0.000 description 28
- 239000003814 drug Substances 0.000 description 21
- 238000004519 manufacturing process Methods 0.000 description 20
- 230000027455 binding Effects 0.000 description 18
- 210000004556 brain Anatomy 0.000 description 17
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- 239000000523 sample Substances 0.000 description 15
- 108010041986 DNA Vaccines Proteins 0.000 description 13
- 229940021995 DNA vaccine Drugs 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 241000282412 Homo Species 0.000 description 11
- 108010071690 Prealbumin Proteins 0.000 description 11
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Chemical compound OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 11
- 102000009190 Transthyretin Human genes 0.000 description 11
- 108010094108 Amyloid Proteins 0.000 description 10
- 102000001049 Amyloid Human genes 0.000 description 10
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 10
- 208000018756 Variant Creutzfeldt-Jakob disease Diseases 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 210000004369 blood Anatomy 0.000 description 10
- 239000008280 blood Substances 0.000 description 10
- 239000000872 buffer Substances 0.000 description 9
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 8
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 8
- 206010012289 Dementia Diseases 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- 208000010544 human prion disease Diseases 0.000 description 8
- 230000003228 microsomal effect Effects 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 102000004169 proteins and genes Human genes 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 206010064553 Dialysis amyloidosis Diseases 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 230000000968 intestinal effect Effects 0.000 description 7
- 210000001589 microsome Anatomy 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 210000001519 tissue Anatomy 0.000 description 7
- 241000282994 Cervidae Species 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 208000024777 Prion disease Diseases 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- 208000014644 Brain disease Diseases 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 5
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 5
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 5
- 102000002004 Cytochrome P-450 Enzyme System Human genes 0.000 description 5
- 108010015742 Cytochrome P-450 Enzyme System Proteins 0.000 description 5
- 208000032274 Encephalopathy Diseases 0.000 description 5
- 241000772415 Neovison vison Species 0.000 description 5
- 208000005881 bovine spongiform encephalopathy Diseases 0.000 description 5
- 239000011575 calcium Substances 0.000 description 5
- 229910052791 calcium Inorganic materials 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- JYWJULGYGOLCGW-UHFFFAOYSA-N chloromethyl chloroformate Chemical compound ClCOC(Cl)=O JYWJULGYGOLCGW-UHFFFAOYSA-N 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 230000001419 dependent effect Effects 0.000 description 5
- 238000010828 elution Methods 0.000 description 5
- 230000005284 excitation Effects 0.000 description 5
- 208000019715 inherited Creutzfeldt-Jakob disease Diseases 0.000 description 5
- 210000000936 intestine Anatomy 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- 210000002381 plasma Anatomy 0.000 description 5
- 101150106357 slc32a1 gene Proteins 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- 241000282979 Alces alces Species 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 206010042938 Systemic candida Diseases 0.000 description 4
- RAMYCVMRCSNXGX-UHFFFAOYSA-N chloromethyl oxan-4-yl carbonate Chemical compound ClCOC(=O)OC1CCOCC1 RAMYCVMRCSNXGX-UHFFFAOYSA-N 0.000 description 4
- 230000002708 enhancing effect Effects 0.000 description 4
- 230000002440 hepatic effect Effects 0.000 description 4
- 230000003993 interaction Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 208000036732 invasive candidiasis Diseases 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 210000001853 liver microsome Anatomy 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 210000000056 organ Anatomy 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 230000009885 systemic effect Effects 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- 102000004506 Blood Proteins Human genes 0.000 description 3
- 108010017384 Blood Proteins Proteins 0.000 description 3
- 108010047041 Complementarity Determining Regions Proteins 0.000 description 3
- 238000011238 DNA vaccination Methods 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 241000287828 Gallus gallus Species 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000000538 analytical sample Substances 0.000 description 3
- 239000000074 antisense oligonucleotide Substances 0.000 description 3
- 238000012230 antisense oligonucleotides Methods 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 230000002490 cerebral effect Effects 0.000 description 3
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000000779 depleting effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 3
- 230000006870 function Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 238000004949 mass spectrometry Methods 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 239000002207 metabolite Substances 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- LMYJGUNNJIDROI-UHFFFAOYSA-N oxan-4-ol Chemical compound OC1CCOCC1 LMYJGUNNJIDROI-UHFFFAOYSA-N 0.000 description 3
- 238000011533 pre-incubation Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 230000007704 transition Effects 0.000 description 3
- LKQIMRCLFVAPHV-UHFFFAOYSA-N 1-[1-(2,2-dimethylpropanoyloxy)ethoxy]ethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(C)OC(C)OC(=O)C(C)(C)C LKQIMRCLFVAPHV-UHFFFAOYSA-N 0.000 description 2
- ZYSHWMOCIONRRR-UHFFFAOYSA-N 3-butanoyl-7-methoxychromen-2-one Chemical compound C1=C(OC)C=C2OC(=O)C(C(=O)CCC)=CC2=C1 ZYSHWMOCIONRRR-UHFFFAOYSA-N 0.000 description 2
- GWMGUFTYUOYYQV-UHFFFAOYSA-N 7-methoxy-4-(methylaminomethyl)chromen-2-one Chemical compound C1=C(OC)C=CC2=C1OC(=O)C=C2CNC GWMGUFTYUOYYQV-UHFFFAOYSA-N 0.000 description 2
- SIDLHXXVIBTSJZ-UHFFFAOYSA-N 7-phenylmethoxyquinoline Chemical compound C=1C=C2C=CC=NC2=CC=1OCC1=CC=CC=C1 SIDLHXXVIBTSJZ-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 108010077544 Chromatin Proteins 0.000 description 2
- 206010063045 Effusion Diseases 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 241001529936 Murinae Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 206010057249 Phagocytosis Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- CVASMYWHWRNWOX-UHFFFAOYSA-N chloro methyl carbonate Chemical compound COC(=O)OCl CVASMYWHWRNWOX-UHFFFAOYSA-N 0.000 description 2
- 210000003483 chromatin Anatomy 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 230000004154 complement system Effects 0.000 description 2
- 238000012790 confirmation Methods 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 230000008034 disappearance Effects 0.000 description 2
- 238000000132 electrospray ionisation Methods 0.000 description 2
- 210000001842 enterocyte Anatomy 0.000 description 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 2
- 230000002163 immunogen Effects 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 206010023497 kuru Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 230000004770 neurodegeneration Effects 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 230000008782 phagocytosis Effects 0.000 description 2
- 238000011170 pharmaceutical development Methods 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000017854 proteolysis Effects 0.000 description 2
- 230000000087 stabilizing effect Effects 0.000 description 2
- 239000011550 stock solution Substances 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 2
- 201000007905 transthyretin amyloidosis Diseases 0.000 description 2
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- JZIMGKLVQCYNHJ-UHFFFAOYSA-N 2-[7-methoxy-2-oxo-4-(trifluoromethyl)chromen-3-yl]acetic acid Chemical compound FC(F)(F)C1=C(CC(O)=O)C(=O)OC2=CC(OC)=CC=C21 JZIMGKLVQCYNHJ-UHFFFAOYSA-N 0.000 description 1
- OVAWAJRNDPSGHE-UHFFFAOYSA-N 2-methyloxolane;hydrate Chemical compound O.CC1CCCO1 OVAWAJRNDPSGHE-UHFFFAOYSA-N 0.000 description 1
- 102100031126 6-phosphogluconolactonase Human genes 0.000 description 1
- 108010029731 6-phosphogluconolactonase Proteins 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 1
- 239000005695 Ammonium acetate Substances 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- 208000036487 Arthropathies Diseases 0.000 description 1
- 230000007082 Aβ accumulation Effects 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 239000006171 Britton–Robinson buffer Substances 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 101100324465 Caenorhabditis elegans arr-1 gene Proteins 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 208000018652 Closed Head injury Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- NBSCHQHZLSJFNQ-GASJEMHNSA-N D-Glucose 6-phosphate Chemical compound OC1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H](O)[C@H]1O NBSCHQHZLSJFNQ-GASJEMHNSA-N 0.000 description 1
- 206010013710 Drug interaction Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 201000011240 Frontotemporal dementia Diseases 0.000 description 1
- 108010058643 Fungal Proteins Proteins 0.000 description 1
- 206010017533 Fungal infection Diseases 0.000 description 1
- VFRROHXSMXFLSN-UHFFFAOYSA-N Glc6P Natural products OP(=O)(O)OCC(O)C(O)C(O)C(O)C=O VFRROHXSMXFLSN-UHFFFAOYSA-N 0.000 description 1
- 108010018962 Glucosephosphate Dehydrogenase Proteins 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101100054311 Homo sapiens ABCC8 gene Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 102000016844 Immunoglobulin-like domains Human genes 0.000 description 1
- 108050006430 Immunoglobulin-like domains Proteins 0.000 description 1
- 208000012659 Joint disease Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100314149 Mus musculus Tnk1 gene Proteins 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 240000006711 Pistacia vera Species 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000002067 Protein Subunits Human genes 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 108010067787 Proteoglycans Proteins 0.000 description 1
- 102000016611 Proteoglycans Human genes 0.000 description 1
- 101150107341 RERE gene Proteins 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 101100271216 Trypanosoma brucei brucei TBA1 gene Proteins 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 235000019257 ammonium acetate Nutrition 0.000 description 1
- 229940043376 ammonium acetate Drugs 0.000 description 1
- XYXNTHIYBIDHGM-UHFFFAOYSA-N ammonium thiosulfate Chemical compound [NH4+].[NH4+].[O-]S([O-])(=O)=S XYXNTHIYBIDHGM-UHFFFAOYSA-N 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000003396 anti-opsonic effect Effects 0.000 description 1
- 239000000427 antigen Substances 0.000 description 1
- 102000025171 antigen binding proteins Human genes 0.000 description 1
- 108091000831 antigen binding proteins Proteins 0.000 description 1
- 102000036639 antigens Human genes 0.000 description 1
- 108091007433 antigens Proteins 0.000 description 1
- 230000001640 apoptogenic effect Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 210000001188 articular cartilage Anatomy 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011888 autopsy Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- HXGBHZIIPPIRQO-UHFFFAOYSA-N dichloromethane;n,n-dimethylpyridin-2-amine Chemical compound ClCCl.CN(C)C1=CC=CC=N1 HXGBHZIIPPIRQO-UHFFFAOYSA-N 0.000 description 1
- 239000012470 diluted sample Substances 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000008406 drug-drug interaction Effects 0.000 description 1
- 239000008157 edible vegetable oil Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 230000035557 fibrillogenesis Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 1
- 239000007850 fluorescent dye Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 210000004051 gastric juice Anatomy 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000002480 immunoprotective effect Effects 0.000 description 1
- 230000001024 immunotherapeutic effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 210000005007 innate immune system Anatomy 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 210000000281 joint capsule Anatomy 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000027928 long-term synaptic potentiation Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 210000004940 nucleus Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003349 osteoarthritic effect Effects 0.000 description 1
- 230000000242 pagocytic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000000634 powder X-ray diffraction Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- SAALQYKUFCIMHR-UHFFFAOYSA-N propan-2-ol;2-propan-2-yloxypropane Chemical compound CC(C)O.CC(C)OC(C)C SAALQYKUFCIMHR-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 230000009870 specific binding Effects 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 210000001179 synovial fluid Anatomy 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000012250 transgenic expression Methods 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 230000001018 virulence Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/4025—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil not condensed and containing further heterocyclic rings, e.g. cromakalim
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
- A61K39/39533—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals
- A61K39/3955—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum against materials from animals against proteinaceous materials, e.g. enzymes, hormones, lymphokines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Hematology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1407506.3A GB201407506D0 (en) | 2014-04-29 | 2014-04-29 | Novel compound |
| PCT/EP2015/058998 WO2015165833A1 (en) | 2014-04-29 | 2015-04-27 | A prodrug of 1,1'-(1,6-dioxo-1,6-hexanediyl)bis-d-proline |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| EA201692185A1 EA201692185A1 (ru) | 2017-06-30 |
| EA032129B1 true EA032129B1 (ru) | 2019-04-30 |
Family
ID=50972033
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EA201692185A EA032129B1 (ru) | 2014-04-29 | 2015-04-27 | Пролекарство 1,1'-(1,6-диоксо-1,6-гександиил)бис-d-пролина |
Country Status (26)
| Country | Link |
|---|---|
| US (3) | US9701668B2 (enExample) |
| EP (1) | EP3137457B1 (enExample) |
| JP (1) | JP6445046B2 (enExample) |
| KR (1) | KR20160145617A (enExample) |
| CN (1) | CN106459016B (enExample) |
| AR (1) | AR100204A1 (enExample) |
| AU (1) | AU2015252184B2 (enExample) |
| BR (1) | BR112016025129A2 (enExample) |
| CA (1) | CA2947060C (enExample) |
| CL (1) | CL2016002721A1 (enExample) |
| CR (1) | CR20160508A (enExample) |
| DO (1) | DOP2016000292A (enExample) |
| EA (1) | EA032129B1 (enExample) |
| ES (1) | ES2731253T3 (enExample) |
| GB (1) | GB201407506D0 (enExample) |
| IL (2) | IL248249A0 (enExample) |
| MA (1) | MA39406B1 (enExample) |
| MX (1) | MX2016014246A (enExample) |
| MY (1) | MY191088A (enExample) |
| PE (1) | PE20161558A1 (enExample) |
| PH (1) | PH12016502006B1 (enExample) |
| SG (1) | SG11201608371RA (enExample) |
| TW (1) | TWI676624B (enExample) |
| UA (1) | UA119871C2 (enExample) |
| UY (1) | UY36098A (enExample) |
| WO (1) | WO2015165833A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9737505B2 (en) | 2014-04-29 | 2017-08-22 | Glaxosmithkline Intellectual Property Development Limited | Prodrug of 1,1′-(1,6-dioxo-1,6-hexanediyl)bis-D-proline |
| GB201518950D0 (en) | 2015-10-27 | 2015-12-09 | Glaxosmithkline Ip Dev Ltd | Compound |
| GB202213162D0 (en) | 2022-09-08 | 2022-10-26 | Cambridge Entpr Ltd | Prodrugs |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003051836A1 (en) * | 2001-12-14 | 2003-06-26 | F. Hoffmann-La Roche Ag | Prodrugs to d-prolines |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT915088E (pt) | 1997-10-31 | 2003-01-31 | Hoffmann La Roche | Derivados de d-prolina |
| EP1636240A1 (en) | 2003-06-05 | 2006-03-22 | Pfizer Products Inc. | Beta-lactamase inhibitor prodrug |
| GB0313386D0 (en) | 2003-06-10 | 2003-07-16 | Univ London | Treatment of disease |
| EP1870412A4 (en) | 2005-04-12 | 2009-12-30 | Meiji Seika Kaisha | 2-THIOETHENYLCARBAPENEM DERIVATIVE |
| GB0712503D0 (en) | 2007-06-27 | 2007-08-08 | Therapeutics Pentraxin Ltd | Use |
| UA108227C2 (xx) | 2010-03-03 | 2015-04-10 | Антигензв'язуючий білок | |
| US9737505B2 (en) | 2014-04-29 | 2017-08-22 | Glaxosmithkline Intellectual Property Development Limited | Prodrug of 1,1′-(1,6-dioxo-1,6-hexanediyl)bis-D-proline |
-
2014
- 2014-04-29 GB GBGB1407506.3A patent/GB201407506D0/en not_active Ceased
-
2015
- 2015-04-27 KR KR1020167029703A patent/KR20160145617A/ko not_active Ceased
- 2015-04-27 JP JP2016565212A patent/JP6445046B2/ja not_active Expired - Fee Related
- 2015-04-27 CN CN201580023347.0A patent/CN106459016B/zh not_active Expired - Fee Related
- 2015-04-27 CA CA2947060A patent/CA2947060C/en active Active
- 2015-04-27 EA EA201692185A patent/EA032129B1/ru not_active IP Right Cessation
- 2015-04-27 AU AU2015252184A patent/AU2015252184B2/en not_active Ceased
- 2015-04-27 MA MA39406A patent/MA39406B1/fr unknown
- 2015-04-27 US US14/787,608 patent/US9701668B2/en not_active Expired - Fee Related
- 2015-04-27 ES ES15720312T patent/ES2731253T3/es active Active
- 2015-04-27 TW TW104113338A patent/TWI676624B/zh not_active IP Right Cessation
- 2015-04-27 MX MX2016014246A patent/MX2016014246A/es active IP Right Grant
- 2015-04-27 MY MYPI2016703952A patent/MY191088A/en unknown
- 2015-04-27 CR CR20160508A patent/CR20160508A/es unknown
- 2015-04-27 EP EP15720312.6A patent/EP3137457B1/en active Active
- 2015-04-27 PE PE2016001934A patent/PE20161558A1/es unknown
- 2015-04-27 UA UAA201612105A patent/UA119871C2/uk unknown
- 2015-04-27 SG SG11201608371RA patent/SG11201608371RA/en unknown
- 2015-04-27 UY UY0001036098A patent/UY36098A/es not_active Application Discontinuation
- 2015-04-27 BR BR112016025129A patent/BR112016025129A2/pt not_active Application Discontinuation
- 2015-04-27 WO PCT/EP2015/058998 patent/WO2015165833A1/en not_active Ceased
- 2015-04-27 AR ARP150101262A patent/AR100204A1/es active IP Right Grant
-
2016
- 2016-10-09 IL IL248249A patent/IL248249A0/en active IP Right Grant
- 2016-10-10 PH PH12016502006A patent/PH12016502006B1/en unknown
- 2016-10-26 CL CL2016002721A patent/CL2016002721A1/es unknown
- 2016-10-28 DO DO2016000292A patent/DOP2016000292A/es unknown
-
2017
- 2017-06-01 US US15/610,984 patent/US9873686B2/en active Active
- 2017-12-11 US US15/837,297 patent/US10597385B2/en active Active
-
2020
- 2020-12-01 IL IL279120A patent/IL279120A/en unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003051836A1 (en) * | 2001-12-14 | 2003-06-26 | F. Hoffmann-La Roche Ag | Prodrugs to d-prolines |
Non-Patent Citations (1)
| Title |
|---|
| AESOP CHO: "Recent Advances in Oral Prodrug Discovery", ANNUAL REPORTS IN MEDICINAL CHEMISTRY, ACADEMIC PRESS, US, vol. 41, 1 January 2006 (2006-01-01), US, pages 395 - 407, XP009184520, ISSN: 0065-7743 * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US11981636B2 (en) | Compositions for treating neurodegenerative diseases | |
| CN114026093A (zh) | 用于治疗神经退行性疾病和线粒体疾病的组合物及其使用方法 | |
| EA032129B1 (ru) | Пролекарство 1,1'-(1,6-диоксо-1,6-гександиил)бис-d-пролина | |
| US9737505B2 (en) | Prodrug of 1,1′-(1,6-dioxo-1,6-hexanediyl)bis-D-proline | |
| Zhang et al. | Design, synthesis, and bioevaluation of novel NLRP3 inhibitor with IBD immunotherapy from the virtual screen | |
| CN113365614A (zh) | 作为神经保护剂的spak激酶抑制剂 | |
| JP7053762B2 (ja) | Ｓａｐ枯渇剤としてのｄ－プロリン誘導体 | |
| EP4501918A1 (en) | 3-phenylisoxazole derivative, and pharmaceutical composition for preventing or treating eye disease, containing same as active ingredient | |
| JP2021520413A (ja) | 眼科的状態のための療法 | |
| US20200360366A1 (en) | Prolylhydroxylase/atf4 inhibitors and methods of use for treating neural cell injury or death and conditions resulting therefrom | |
| US20230278983A1 (en) | Indole derivatives and uses thereof for treating a cancer | |
| JP2021520412A (ja) | タンパク質ミスフォールディング疾患のための療法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Lapse of a eurasian patent due to non-payment of renewal fees within the time limit in the following designated state(s) |
Designated state(s): AM KG TM |