RU2705206C2 - Композиции и способы лечения анемии - Google Patents
Композиции и способы лечения анемии Download PDFInfo
- Publication number
- RU2705206C2 RU2705206C2 RU2016100363A RU2016100363A RU2705206C2 RU 2705206 C2 RU2705206 C2 RU 2705206C2 RU 2016100363 A RU2016100363 A RU 2016100363A RU 2016100363 A RU2016100363 A RU 2016100363A RU 2705206 C2 RU2705206 C2 RU 2705206C2
- Authority
- RU
- Russia
- Prior art keywords
- compound
- formula
- anemia
- patient
- approximately
- Prior art date
Links
- 208000007502 anemia Diseases 0.000 title claims abstract description 332
- 238000000034 method Methods 0.000 title claims abstract description 176
- 239000000203 mixture Substances 0.000 title description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 971
- 108090000394 Erythropoietin Proteins 0.000 claims abstract description 252
- 102000003951 Erythropoietin Human genes 0.000 claims abstract description 251
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims abstract description 243
- 229940105423 erythropoietin Drugs 0.000 claims abstract description 239
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims abstract description 232
- 230000001965 increasing effect Effects 0.000 claims abstract description 117
- 229910052742 iron Inorganic materials 0.000 claims abstract description 116
- JGRXMPYUTJLTKT-UHFFFAOYSA-N 2-[[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid Chemical compound C1=C(O)C(C(=O)NCC(=O)O)=NC=C1C1=CC=CC(Cl)=C1 JGRXMPYUTJLTKT-UHFFFAOYSA-N 0.000 claims abstract description 98
- 239000003814 drug Substances 0.000 claims abstract description 15
- 108010054147 Hemoglobins Proteins 0.000 claims description 348
- 102000001554 Hemoglobins Human genes 0.000 claims description 348
- 208000020832 chronic kidney disease Diseases 0.000 claims description 225
- 150000003839 salts Chemical class 0.000 claims description 200
- 238000011282 treatment Methods 0.000 claims description 35
- 238000005259 measurement Methods 0.000 claims description 27
- 239000003173 antianemic agent Substances 0.000 claims description 22
- 229940125367 erythropoiesis stimulating agent Drugs 0.000 claims description 22
- 230000007423 decrease Effects 0.000 claims description 19
- 238000002512 chemotherapy Methods 0.000 claims description 13
- 239000013589 supplement Substances 0.000 claims description 13
- 229940079593 drug Drugs 0.000 claims description 12
- 239000000654 additive Substances 0.000 claims description 11
- 230000000996 additive effect Effects 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 9
- 108010002601 epoetin beta Proteins 0.000 claims description 7
- 229960004579 epoetin beta Drugs 0.000 claims description 7
- 108010083444 peginesatide Proteins 0.000 claims description 7
- 229960004772 peginesatide Drugs 0.000 claims description 7
- 208000030507 AIDS Diseases 0.000 claims description 6
- 102000008857 Ferritin Human genes 0.000 claims description 6
- 108050000784 Ferritin Proteins 0.000 claims description 6
- 238000008416 Ferritin Methods 0.000 claims description 6
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- XJOTXKZIRSHZQV-RXHOOSIZSA-N (3S)-3-amino-4-[[(2S,3R)-1-[[(2S)-1-[[(2S)-1-[(2S)-2-[[(2S,3S)-1-[[(1R,6R,12R,17R,20S,23S,26R,31R,34R,39R,42S,45S,48S,51S,59S)-51-(4-aminobutyl)-31-[[(2S)-6-amino-1-[[(1S,2R)-1-carboxy-2-hydroxypropyl]amino]-1-oxohexan-2-yl]carbamoyl]-20-benzyl-23-[(2S)-butan-2-yl]-45-(3-carbamimidamidopropyl)-48-(hydroxymethyl)-42-(1H-imidazol-4-ylmethyl)-59-(2-methylsulfanylethyl)-7,10,19,22,25,33,40,43,46,49,52,54,57,60,63,64-hexadecaoxo-3,4,14,15,28,29,36,37-octathia-8,11,18,21,24,32,41,44,47,50,53,55,58,61,62,65-hexadecazatetracyclo[32.19.8.26,17.212,39]pentahexacontan-26-yl]amino]-3-methyl-1-oxopentan-2-yl]carbamoyl]pyrrolidin-1-yl]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-oxobutanoic acid Chemical compound CC[C@H](C)[C@H](NC(=O)[C@@H]1CCCN1C(=O)[C@H](Cc1ccccc1)NC(=O)[C@H](Cc1cnc[nH]1)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(O)=O)[C@@H](C)O)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@@H]2CSSC[C@@H]3NC(=O)[C@@H]4CSSC[C@H](NC(=O)[C@H](Cc5ccccc5)NC(=O)[C@@H](NC1=O)[C@@H](C)CC)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](Cc1cnc[nH]1)NC3=O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N2)C(=O)NCC(=O)N4)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O XJOTXKZIRSHZQV-RXHOOSIZSA-N 0.000 abstract description 54
- 108060003558 hepcidin Proteins 0.000 abstract description 54
- 102000018511 hepcidin Human genes 0.000 abstract description 53
- 229940066919 hepcidin Drugs 0.000 abstract description 53
- 230000000694 effects Effects 0.000 abstract description 24
- 239000000126 substance Substances 0.000 abstract description 6
- 230000002035 prolonged effect Effects 0.000 abstract description 4
- 230000002354 daily effect Effects 0.000 description 243
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 215
- 239000002207 metabolite Substances 0.000 description 194
- 201000010099 disease Diseases 0.000 description 176
- 239000012453 solvate Substances 0.000 description 173
- 239000003381 stabilizer Substances 0.000 description 148
- 229940125904 compound 1 Drugs 0.000 description 146
- 210000002966 serum Anatomy 0.000 description 143
- YOZBGTLTNGAVFU-UHFFFAOYSA-N roxadustat Chemical compound C1=C2C(C)=NC(C(=O)NCC(O)=O)=C(O)C2=CC=C1OC1=CC=CC=C1 YOZBGTLTNGAVFU-UHFFFAOYSA-N 0.000 description 129
- 229940113151 HIF prolyl hydroxylase inhibitor Drugs 0.000 description 127
- 229940125898 compound 5 Drugs 0.000 description 104
- 229940125773 compound 10 Drugs 0.000 description 103
- 229940125782 compound 2 Drugs 0.000 description 103
- 229940126214 compound 3 Drugs 0.000 description 102
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 102
- 229940125797 compound 12 Drugs 0.000 description 99
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 98
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 97
- RRSNDVCODIMOFX-MPKOGUQCSA-N Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O Chemical compound Fc1c(Cl)cccc1[C@H]1[C@@H](NC2(CCCCC2)[C@@]11C(=O)Nc2cc(Cl)ccc12)C(=O)Nc1ccc(cc1)C(=O)NCCCCCc1cccc2C(=O)N(Cc12)C1CCC(=O)NC1=O RRSNDVCODIMOFX-MPKOGUQCSA-N 0.000 description 97
- 238000004519 manufacturing process Methods 0.000 description 96
- PXWOWORYDKAEJO-UHFFFAOYSA-N 2-[[5-(3-fluorophenyl)-3-hydroxypyridine-2-carbonyl]amino]acetic acid Chemical compound C1=C(O)C(C(=O)NCC(=O)O)=NC=C1C1=CC=CC(F)=C1 PXWOWORYDKAEJO-UHFFFAOYSA-N 0.000 description 71
- 230000003247 decreasing effect Effects 0.000 description 60
- 108010043005 Prolyl Hydroxylases Proteins 0.000 description 43
- 102000004079 Prolyl Hydroxylases Human genes 0.000 description 43
- 230000002829 reductive effect Effects 0.000 description 40
- 208000035475 disorder Diseases 0.000 description 39
- -1 heterocyclic carboxamide Chemical class 0.000 description 38
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 37
- 230000032683 aging Effects 0.000 description 20
- 229910052739 hydrogen Inorganic materials 0.000 description 19
- 206010019280 Heart failures Diseases 0.000 description 17
- 230000009424 thromboembolic effect Effects 0.000 description 17
- 230000005764 inhibitory process Effects 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 15
- 210000000748 cardiovascular system Anatomy 0.000 description 15
- 108010018033 endothelial PAS domain-containing protein 1 Proteins 0.000 description 15
- 210000001519 tissue Anatomy 0.000 description 15
- 239000001257 hydrogen Substances 0.000 description 14
- 235000011054 acetic acid Nutrition 0.000 description 13
- 210000004369 blood Anatomy 0.000 description 13
- 239000008280 blood Substances 0.000 description 13
- 210000004027 cell Anatomy 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 13
- 229910052760 oxygen Inorganic materials 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 12
- 230000000087 stabilizing effect Effects 0.000 description 12
- 206010021143 Hypoxia Diseases 0.000 description 11
- 230000001684 chronic effect Effects 0.000 description 11
- 239000001301 oxygen Substances 0.000 description 11
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 10
- 241000282414 Homo sapiens Species 0.000 description 10
- 102100022875 Hypoxia-inducible factor 1-alpha Human genes 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 230000000302 ischemic effect Effects 0.000 description 10
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 description 9
- 206010007559 Cardiac failure congestive Diseases 0.000 description 9
- 208000018262 Peripheral vascular disease Diseases 0.000 description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 9
- 230000007954 hypoxia Effects 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 8
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 8
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 8
- 208000029078 coronary artery disease Diseases 0.000 description 8
- 125000000753 cycloalkyl group Chemical group 0.000 description 8
- 201000000523 end stage renal failure Diseases 0.000 description 8
- 108020004999 messenger RNA Proteins 0.000 description 8
- 208000024891 symptom Diseases 0.000 description 8
- 102100037249 Egl nine homolog 1 Human genes 0.000 description 7
- 102100032742 Histone-lysine N-methyltransferase SETD2 Human genes 0.000 description 7
- 101000654725 Homo sapiens Histone-lysine N-methyltransferase SETD2 Proteins 0.000 description 7
- 102100037247 Prolyl hydroxylase EGLN3 Human genes 0.000 description 7
- 108091006976 SLC40A1 Proteins 0.000 description 7
- 102000004338 Transferrin Human genes 0.000 description 7
- 108090000901 Transferrin Proteins 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 201000011510 cancer Diseases 0.000 description 7
- 125000001072 heteroaryl group Chemical group 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 239000012581 transferrin Substances 0.000 description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 208000017667 Chronic Disease Diseases 0.000 description 6
- 101710111663 Egl nine homolog 1 Proteins 0.000 description 6
- 102100036448 Endothelial PAS domain-containing protein 1 Human genes 0.000 description 6
- 101710170720 Prolyl hydroxylase EGLN3 Proteins 0.000 description 6
- 125000003118 aryl group Chemical group 0.000 description 6
- 150000001768 cations Chemical class 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 6
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 6
- 230000001575 pathological effect Effects 0.000 description 6
- 235000018102 proteins Nutrition 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 230000004044 response Effects 0.000 description 6
- 208000007056 sickle cell anemia Diseases 0.000 description 6
- 238000013518 transcription Methods 0.000 description 6
- 230000035897 transcription Effects 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
- 208000005176 Hepatitis C Diseases 0.000 description 5
- 101001046870 Homo sapiens Hypoxia-inducible factor 1-alpha Proteins 0.000 description 5
- 108050009527 Hypoxia-inducible factor-1 alpha Proteins 0.000 description 5
- 206010022971 Iron Deficiencies Diseases 0.000 description 5
- 201000003793 Myelodysplastic syndrome Diseases 0.000 description 5
- 229940078467 Prolyl hydroxylase inhibitor Drugs 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000033115 angiogenesis Effects 0.000 description 5
- 210000001185 bone marrow Anatomy 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 230000002060 circadian Effects 0.000 description 5
- 230000001276 controlling effect Effects 0.000 description 5
- 210000003743 erythrocyte Anatomy 0.000 description 5
- 208000028867 ischemia Diseases 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000006641 stabilisation Effects 0.000 description 5
- 238000011105 stabilization Methods 0.000 description 5
- 229910052717 sulfur Inorganic materials 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 208000002670 vitamin B12 deficiency Diseases 0.000 description 5
- LEINOXRFIYQSFV-ZPGRZCPFSA-N (3s)-n-[(2s)-6-amino-1-(2,2-diphenylethylamino)-1-oxohexan-2-yl]-2-(4-oxo-4-phenylbutanoyl)-3,4-dihydro-1h-isoquinoline-3-carboxamide Chemical compound C([C@H]1C(=O)N[C@@H](CCCCN)C(=O)NCC(C=2C=CC=CC=2)C=2C=CC=CC=2)C2=CC=CC=C2CN1C(=O)CCC(=O)C1=CC=CC=C1 LEINOXRFIYQSFV-ZPGRZCPFSA-N 0.000 description 4
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 description 4
- 206010007558 Cardiac failure chronic Diseases 0.000 description 4
- 102100031181 Glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- 102100037248 Prolyl hydroxylase EGLN2 Human genes 0.000 description 4
- 206010043395 Thalassaemia sickle cell Diseases 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000002648 combination therapy Methods 0.000 description 4
- 238000000502 dialysis Methods 0.000 description 4
- 238000002651 drug therapy Methods 0.000 description 4
- 208000028208 end stage renal disease Diseases 0.000 description 4
- 230000006870 function Effects 0.000 description 4
- 229930182480 glucuronide Natural products 0.000 description 4
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 4
- 238000001631 haemodialysis Methods 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 230000000322 hemodialysis Effects 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 230000010438 iron metabolism Effects 0.000 description 4
- 208000017169 kidney disease Diseases 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- 206010028537 myelofibrosis Diseases 0.000 description 4
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 4
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical group NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 4
- 208000003476 primary myelofibrosis Diseases 0.000 description 4
- ZEXKKIXCRDTKBF-UHFFFAOYSA-N quinoline-2-carboxamide Chemical compound C1=CC=CC2=NC(C(=O)N)=CC=C21 ZEXKKIXCRDTKBF-UHFFFAOYSA-N 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 201000000306 sarcoidosis Diseases 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 208000011231 Crohn disease Diseases 0.000 description 3
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 0.000 description 3
- 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 3
- 102000008133 Iron-Binding Proteins Human genes 0.000 description 3
- 108010035210 Iron-Binding Proteins Proteins 0.000 description 3
- 208000035901 Ischaemic ulcer Diseases 0.000 description 3
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
- QGDDYKZZAHEQLD-UHFFFAOYSA-N O.FC=1C=C(C=CC1)C=1C=C(C(=NC1)C(=O)NCC(=O)O)O Chemical compound O.FC=1C=C(C=CC1)C=1C=C(C(=NC1)C(=O)NCC(=O)O)O QGDDYKZZAHEQLD-UHFFFAOYSA-N 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 3
- 101710170760 Prolyl hydroxylase EGLN2 Proteins 0.000 description 3
- 201000004681 Psoriasis Diseases 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000003143 atherosclerotic effect Effects 0.000 description 3
- 238000004166 bioassay Methods 0.000 description 3
- 230000017531 blood circulation Effects 0.000 description 3
- 235000021152 breakfast Nutrition 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 125000004122 cyclic group Chemical group 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 206010012601 diabetes mellitus Diseases 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 201000011066 hemangioma Diseases 0.000 description 3
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 description 3
- 229960000890 hydrocortisone Drugs 0.000 description 3
- 229910052740 iodine Inorganic materials 0.000 description 3
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 3
- 229910052744 lithium Inorganic materials 0.000 description 3
- 210000004165 myocardium Anatomy 0.000 description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 description 3
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000007686 potassium Nutrition 0.000 description 3
- 239000011591 potassium Substances 0.000 description 3
- 229910052700 potassium Inorganic materials 0.000 description 3
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 210000002027 skeletal muscle Anatomy 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000015424 sodium Nutrition 0.000 description 3
- 230000004936 stimulating effect Effects 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- 239000011593 sulfur Chemical group 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000000451 tissue damage Effects 0.000 description 3
- 231100000827 tissue damage Toxicity 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000029663 wound healing Effects 0.000 description 3
- AOFUBOWZWQFQJU-SNOJBQEQSA-N (2r,3s,4s,5r)-2,5-bis(hydroxymethyl)oxolane-2,3,4-triol;(2s,3r,4s,5s,6r)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O.OC[C@H]1O[C@H](O)[C@H](O)[C@@H](O)[C@@H]1O AOFUBOWZWQFQJU-SNOJBQEQSA-N 0.000 description 2
- IMWCPTKSESEZCL-SPSNFJOYSA-H (e)-but-2-enedioate;iron(3+) Chemical compound [Fe+3].[Fe+3].[O-]C(=O)\C=C\C([O-])=O.[O-]C(=O)\C=C\C([O-])=O.[O-]C(=O)\C=C\C([O-])=O IMWCPTKSESEZCL-SPSNFJOYSA-H 0.000 description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 2
- 125000005917 3-methylpentyl group Chemical group 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 2
- 206010003130 Arrhythmia supraventricular Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 201000001320 Atherosclerosis Diseases 0.000 description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
- 229940122439 Hydroxylase inhibitor Drugs 0.000 description 2
- 206010020565 Hyperaemia Diseases 0.000 description 2
- 102100030482 Hypoxia-inducible factor 3-alpha Human genes 0.000 description 2
- 101710083143 Hypoxia-inducible factor 3-alpha Proteins 0.000 description 2
- 206010065973 Iron Overload Diseases 0.000 description 2
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- 108010061951 Methemoglobin Proteins 0.000 description 2
- 102000008109 Mixed Function Oxygenases Human genes 0.000 description 2
- 108010074633 Mixed Function Oxygenases Proteins 0.000 description 2
- 206010033425 Pain in extremity Diseases 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 208000027418 Wounds and injury Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 125000003342 alkenyl group Chemical group 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000304 alkynyl group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000006427 angiogenic response Effects 0.000 description 2
- 125000000129 anionic group Chemical class 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 210000001367 artery Anatomy 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229910052797 bismuth Inorganic materials 0.000 description 2
- JCXGWMGPZLAOME-UHFFFAOYSA-N bismuth atom Chemical compound [Bi] JCXGWMGPZLAOME-UHFFFAOYSA-N 0.000 description 2
- 238000004820 blood count Methods 0.000 description 2
- 230000036770 blood supply Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 230000008822 capillary blood flow Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 210000001638 cerebellum Anatomy 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 210000004351 coronary vessel Anatomy 0.000 description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 230000002526 effect on cardiovascular system Effects 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 210000003013 erythroid precursor cell Anatomy 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 235000015220 hamburgers Nutrition 0.000 description 2
- 210000002216 heart Anatomy 0.000 description 2
- 210000005003 heart tissue Anatomy 0.000 description 2
- 239000000833 heterodimer Substances 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 230000033444 hydroxylation Effects 0.000 description 2
- 238000005805 hydroxylation reaction Methods 0.000 description 2
- 230000001146 hypoxic effect Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 150000002505 iron Chemical class 0.000 description 2
- 229910000358 iron sulfate Inorganic materials 0.000 description 2
- BAUYGSIQEAFULO-UHFFFAOYSA-L iron(2+) sulfate (anhydrous) Chemical compound [Fe+2].[O-]S([O-])(=O)=O BAUYGSIQEAFULO-UHFFFAOYSA-L 0.000 description 2
- QDUZQOIJXPPTLY-IYEMJOQQSA-N iron;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoic acid Chemical compound [Fe].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O QDUZQOIJXPPTLY-IYEMJOQQSA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 230000003278 mimic effect Effects 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000000902 placebo Substances 0.000 description 2
- 229940068196 placebo Drugs 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical group [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000002062 proliferating effect Effects 0.000 description 2
- 230000035755 proliferation Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 230000020874 response to hypoxia Effects 0.000 description 2
- 229910052702 rhenium Inorganic materials 0.000 description 2
- WUAPFZMCVAUBPE-UHFFFAOYSA-N rhenium atom Chemical compound [Re] WUAPFZMCVAUBPE-UHFFFAOYSA-N 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000009097 single-agent therapy Methods 0.000 description 2
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 210000000952 spleen Anatomy 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 230000017423 tissue regeneration Effects 0.000 description 2
- 210000003371 toe Anatomy 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 230000009724 venous congestion Effects 0.000 description 2
- 210000001835 viscera Anatomy 0.000 description 2
- 210000002268 wool Anatomy 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- SMNDYUVBFMFKNZ-UHFFFAOYSA-N 2-furoic acid Chemical compound OC(=O)C1=CC=CO1 SMNDYUVBFMFKNZ-UHFFFAOYSA-N 0.000 description 1
- 125000005916 2-methylpentyl group Chemical group 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- VIHUZJYFQOEUMI-UHFFFAOYSA-N 3-Hydroxypicolinamide Chemical group NC(=O)C1=NC=CC=C1O VIHUZJYFQOEUMI-UHFFFAOYSA-N 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- YRNWIFYIFSBPAU-UHFFFAOYSA-N 4-[4-(dimethylamino)phenyl]-n,n-dimethylaniline Chemical compound C1=CC(N(C)C)=CC=C1C1=CC=C(N(C)C)C=C1 YRNWIFYIFSBPAU-UHFFFAOYSA-N 0.000 description 1
- FWMNVWWHGCHHJJ-SKKKGAJSSA-N 4-amino-1-[(2r)-6-amino-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-amino-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]piperidine-4-carboxylic acid Chemical compound C([C@H](C(=O)N[C@H](CC(C)C)C(=O)N[C@H](CCCCN)C(=O)N1CCC(N)(CC1)C(O)=O)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 FWMNVWWHGCHHJJ-SKKKGAJSSA-N 0.000 description 1
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 1
- 206010000358 Accelerated hypertension Diseases 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 244000144725 Amygdalus communis Species 0.000 description 1
- 235000011437 Amygdalus communis Nutrition 0.000 description 1
- 208000030760 Anaemia of chronic disease Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 208000031104 Arterial Occlusive disease Diseases 0.000 description 1
- 200000000007 Arterial disease Diseases 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 208000002691 Choroiditis Diseases 0.000 description 1
- 208000032064 Chronic Limb-Threatening Ischemia Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 238000002965 ELISA Methods 0.000 description 1
- 238000008157 ELISA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 241000283074 Equus asinus Species 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 101800003310 Hepcidin-25 Proteins 0.000 description 1
- 102400001151 Hepcidin-25 Human genes 0.000 description 1
- 108091027305 Heteroduplex Proteins 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 101000881648 Homo sapiens Egl nine homolog 1 Proteins 0.000 description 1
- 101001021253 Homo sapiens Hepcidin Proteins 0.000 description 1
- 101001071145 Homo sapiens Polyhomeotic-like protein 1 Proteins 0.000 description 1
- 101000583616 Homo sapiens Polyhomeotic-like protein 2 Proteins 0.000 description 1
- 101000583581 Homo sapiens Polyhomeotic-like protein 3 Proteins 0.000 description 1
- 101000881650 Homo sapiens Prolyl hydroxylase EGLN2 Proteins 0.000 description 1
- 101000881678 Homo sapiens Prolyl hydroxylase EGLN3 Proteins 0.000 description 1
- 206010021784 Infected skin ulcer Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 206010022562 Intermittent claudication Diseases 0.000 description 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000031998 Mycobacterium Infections Diseases 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- YENALQMTUSAKLS-UHFFFAOYSA-N O.ClC=1C=C(C=CC1)C=1C=C(C(=NC1)C(=O)NCC(=O)O)O Chemical compound O.ClC=1C=C(C=CC1)C=1C=C(C(=NC1)C(=O)NCC(=O)O)O YENALQMTUSAKLS-UHFFFAOYSA-N 0.000 description 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 description 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 description 1
- 208000010191 Osteitis Deformans Diseases 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000027868 Paget disease Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 206010034576 Peripheral ischaemia Diseases 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- 102100033222 Polyhomeotic-like protein 1 Human genes 0.000 description 1
- 102100030903 Polyhomeotic-like protein 2 Human genes 0.000 description 1
- 102100030905 Polyhomeotic-like protein 3 Human genes 0.000 description 1
- 208000003971 Posterior uveitis Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 206010038848 Retinal detachment Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 206010038933 Retinopathy of prematurity Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative Diseases 0.000 description 1
- 241000191940 Staphylococcus Species 0.000 description 1
- 208000027073 Stargardt disease Diseases 0.000 description 1
- 108010090804 Streptavidin Proteins 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000002903 Thalassemia Diseases 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- 108091023040 Transcription factor Proteins 0.000 description 1
- 102000040945 Transcription factor Human genes 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 206010047663 Vitritis Diseases 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 235000020224 almond Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940024606 amino acid Drugs 0.000 description 1
- 235000001014 amino acid Nutrition 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 208000022400 anemia due to chronic disease Diseases 0.000 description 1
- 208000037868 anemia in chronic kidney disease Diseases 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 208000021328 arterial occlusion Diseases 0.000 description 1
- 208000028922 artery disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 230000008236 biological pathway Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
- 125000000298 cyclopropenyl group Chemical group [H]C1=C([H])C1([H])* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000003544 deproteinization Effects 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000003828 downregulation Effects 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000006911 enzymatic reaction Methods 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 230000000925 erythroid effect Effects 0.000 description 1
- 230000010437 erythropoiesis Effects 0.000 description 1
- 230000000913 erythropoietic effect Effects 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000008134 glucuronides Chemical class 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000005534 hematocrit Methods 0.000 description 1
- 208000034737 hemoglobinopathy Diseases 0.000 description 1
- 208000013653 hyalitis Diseases 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000005945 imidazopyridyl group Chemical group 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000010324 immunological assay Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000018337 inherited hemoglobinopathy Diseases 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 208000021156 intermittent vascular claudication Diseases 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 208000030175 lameness Diseases 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 230000001000 lipidemic effect Effects 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 208000002780 macular degeneration Diseases 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 208000027202 mammary Paget disease Diseases 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 229960003194 meglumine Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- ZXTXADWNRQCBJW-UHFFFAOYSA-N n-(2-aminoethyl)-3-hydroxypyridine-2-carboxamide Chemical compound NCCNC(=O)C1=NC=CC=C1O ZXTXADWNRQCBJW-UHFFFAOYSA-N 0.000 description 1
- 125000006606 n-butoxy group Chemical group 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000005244 neohexyl group Chemical group [H]C([H])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 229960003104 ornithine Drugs 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 125000005968 oxazolinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000003538 pentan-3-yl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 108040007629 peroxidase activity proteins Proteins 0.000 description 1
- 102000013415 peroxidase activity proteins Human genes 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 238000009520 phase I clinical trial Methods 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000005936 piperidyl group Chemical group 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 231100000857 poor renal function Toxicity 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 210000001995 reticulocyte Anatomy 0.000 description 1
- 230000004264 retinal detachment Effects 0.000 description 1
- 230000000250 revascularization Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 238000009666 routine test Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000005306 thianaphthenyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 239000002525 vasculotropin inhibitor Substances 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
Images
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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
-
- 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
- A61K38/1816—Erythropoietin [EPO]
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Physiology (AREA)
- Nutrition Science (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Urology & Nephrology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Pyridine Compounds (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361834808P | 2013-06-13 | 2013-06-13 | |
| US61/834,808 | 2013-06-13 | ||
| US201361889478P | 2013-10-10 | 2013-10-10 | |
| US61/889,478 | 2013-10-10 | ||
| US201361898885P | 2013-11-01 | 2013-11-01 | |
| US201361898890P | 2013-11-01 | 2013-11-01 | |
| US61/898,890 | 2013-11-01 | ||
| US61/898,885 | 2013-11-01 | ||
| US201361912185P | 2013-12-05 | 2013-12-05 | |
| US61/912,185 | 2013-12-05 | ||
| PCT/US2014/040889 WO2014200773A2 (en) | 2013-06-13 | 2014-06-04 | Compositions and methods for treating anemia |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019134558A Division RU2019134558A (ru) | 2013-06-13 | 2014-06-04 | Композиции и способы лечения анемии |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| RU2016100363A RU2016100363A (ru) | 2017-07-18 |
| RU2016100363A3 RU2016100363A3 (enExample) | 2018-05-15 |
| RU2705206C2 true RU2705206C2 (ru) | 2019-11-06 |
Family
ID=52022903
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019134558A RU2019134558A (ru) | 2013-06-13 | 2014-06-04 | Композиции и способы лечения анемии |
| RU2016100363A RU2705206C2 (ru) | 2013-06-13 | 2014-06-04 | Композиции и способы лечения анемии |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019134558A RU2019134558A (ru) | 2013-06-13 | 2014-06-04 | Композиции и способы лечения анемии |
Country Status (37)
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK3026044T3 (en) | 2006-06-26 | 2019-02-18 | Akebia Therapeutics Inc | PROLYL HYDROXYLASE INHIBITORS AND METHODS FOR USE |
| NO2686520T3 (enExample) | 2011-06-06 | 2018-03-17 | ||
| EP2986207B1 (en) | 2013-04-16 | 2024-03-20 | Koninklijke Philips N.V. | System and method for biventricular pacemaker pulse detection in surface ecg |
| DK3007695T3 (da) * | 2013-06-13 | 2024-03-18 | Akebia Therapeutics Inc | Sammensætninger og fremgangsmåder til behandling af anæmi |
| SG10202012791TA (en) | 2013-11-15 | 2021-01-28 | Akebia Therapeutics Inc | Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, compositions, and uses thereof |
| MX2017009417A (es) | 2015-01-23 | 2017-12-07 | Akebia Therapeutics Inc | Formas solidas de acido 2-(5-(3-fluorofenil)-3-hidroxipicolinamido )acetico, composiciones y usos de las mismas. |
| PT3277270T (pt) * | 2015-04-01 | 2021-12-07 | Akebia Therapeutics Inc | Composições e métodos de tratamento de anemia |
| CN108401429A (zh) * | 2016-12-06 | 2018-08-14 | 深圳市塔吉瑞生物医药有限公司 | 一种取代的杂芳基酰胺化合物及包含该化合物的组合物及其用途 |
| WO2019028150A1 (en) | 2017-08-01 | 2019-02-07 | Akebia Therapeutics, Inc. | COMPOSITIONS FOR USE IN METHODS OF TREATING HEMOGLOBINOPATHIES |
| MX2020011845A (es) | 2018-05-09 | 2021-01-15 | Akebia Therapeutics Inc | Proceso para preparar acido 2-[[5-(3-clorofenil)-3-hidroxipiridina -2-carbonil]amino]acetico. |
| CA3159368A1 (en) * | 2019-10-31 | 2021-05-06 | Akebia Therapeutics, Inc. | Therapeutic methods using vadadustat |
| US11524939B2 (en) | 2019-11-13 | 2022-12-13 | Akebia Therapeutics, Inc. | Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid |
| US20230190731A1 (en) * | 2020-03-17 | 2023-06-22 | Zydus Lifesciences Limited | Formulation comprising hif prolyl hydroxylase inhibitors |
| TW202206065A (zh) * | 2020-04-29 | 2022-02-16 | 美商百愛及生物醫藥公司 | 用以治療老化相關病況之缺氧誘導因子脯胺醯羥化酶抑制劑 |
| US20230263786A1 (en) | 2020-06-19 | 2023-08-24 | Akebia Therapeutics, Inc. | Modulation of drug-drug interactions of vadadustat |
| WO2022150623A1 (en) | 2021-01-08 | 2022-07-14 | Akebia Therapeutics, Inc. | Compounds and composition for the treatment of anemia |
| KR20230130035A (ko) * | 2021-01-08 | 2023-09-11 | 아케비아 테라퓨틱스 인코포레이티드 | 바다두스타트를 사용하는 치료 방법 |
| AU2022229275A1 (en) | 2021-03-01 | 2023-10-12 | Akebia Therapeutics, Inc. | Modulation of drug-drug interactions of vadadustat |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070299086A1 (en) * | 2006-06-26 | 2007-12-27 | The Procter & Gamble Company | Prolyl hydroxylase inhibitors and methods of use |
| US20120309977A1 (en) * | 2011-06-06 | 2012-12-06 | Akebia Therapeutics Inc. | Process for preparing [(3-hydroxypyridine-2-carbonyl)amino]alkanoic acids, esters and amides |
Family Cites Families (125)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3655679A (en) | 1969-06-25 | 1972-04-11 | Merck & Co Inc | Certain aryl pyridine carboxylic acid derivatives |
| US3703582A (en) | 1970-04-20 | 1972-11-21 | Merck & Co Inc | Aryl pyridine carboxylic acids in the treatment of inflammation |
| US3894920A (en) | 1971-12-21 | 1975-07-15 | Sagami Chem Res | Process for preparing alkyl-substituted 3,6-dihydro-o-dioxin derivatives |
| US4016287A (en) | 1972-07-17 | 1977-04-05 | Boehringer Ingelheim Gmbh | Dermatological compositions containing an acylamino-carboxylic acid or an alkyl ester thereof |
| CA1261335A (en) | 1984-08-29 | 1989-09-26 | Hoffmann-La Roche Limited/Hoffmann-La Roche Limitee | Ethylenediamine monoamide derivatives |
| CN1023479C (zh) | 1985-09-27 | 1994-01-12 | 弗·哈夫曼-拉罗切有限公司 | 乙二胺的单酰胺衍生物的制备方法 |
| TW219933B (enExample) | 1990-02-26 | 1994-02-01 | Lilly Co Eli | |
| US5405613A (en) | 1991-12-11 | 1995-04-11 | Creative Nutrition Canada Corp. | Vitamin/mineral composition |
| TW352384B (en) | 1992-03-24 | 1999-02-11 | Hoechst Ag | Sulfonamido- or sulfonamidocarbonylpyridine-2-carboxamides, process for their preparation and their use as pharmaceuticals |
| DE4219158A1 (de) | 1992-06-11 | 1993-12-16 | Thomae Gmbh Dr K | Biphenylderivate, diese Verbindungen enthaltende Arzneimittel und Verfahren zu ihrer Herstellung |
| ES2101420T3 (es) | 1993-11-02 | 1997-07-01 | Hoechst Ag | Esteres-amidas de acidos carboxilicos heterociclicos sustituidos, su preparacion y su utilizacion como medicamentos. |
| ATE149486T1 (de) | 1993-11-02 | 1997-03-15 | Hoechst Ag | Substituierte heterocyclische carbonsäureamide, ihre herstellung und ihre verwendung als arzneimittel |
| CA2138929A1 (en) | 1993-12-30 | 1995-07-01 | Klaus Weidmann | Substituted heterocyclic carboxamides, their preparation and their use as pharmaceuticals |
| DE4410480A1 (de) | 1994-03-25 | 1995-09-28 | Hoechst Ag | Sulfonamidocarbonylpyridin-2-carbonsäureesteramide sowie ihre Pyridin-N-oxide, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| DE4410423A1 (de) | 1994-03-25 | 1995-09-28 | Hoechst Ag | Sulfonamidocarbonylpyridin-2-carbonsäureamide sowie ihre Pyridin-N-oxide, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| US5789426A (en) | 1995-01-20 | 1998-08-04 | Cornell Research Foundation, Inc. | Method for the treatment of fibroproliferative disorders by application of inhibitors of protein hydroxylation |
| DE19535571A1 (de) | 1995-09-14 | 1997-03-20 | Boehringer Mannheim Gmbh | Pharmazeutische Kombinationspräparate und deren Verwendung zur Behandlung von Hämodialysepatienten |
| IL135495A (en) | 1995-09-28 | 2002-12-01 | Hoechst Ag | Intermediate compounds for the preparation of quinoline-converted amines - 2 - carboxylic acid |
| JPH09221476A (ja) | 1995-12-15 | 1997-08-26 | Otsuka Pharmaceut Co Ltd | 医薬組成物 |
| CA2253282A1 (en) | 1996-04-30 | 1997-11-06 | Hoechst Aktiengesellschaft | 3-alkoxypyridine-2-carboxylic acid amide esters, their preparation and their use as drugs |
| DE19620041A1 (de) | 1996-05-17 | 1998-01-29 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| DE19650215A1 (de) | 1996-12-04 | 1998-06-10 | Hoechst Ag | 3-Hydroxypyridin-2-carbonsäureamidester, ihre Herstellung und ihre Verwendung als Arzneimittel |
| EP1024134A4 (en) | 1997-10-09 | 2003-05-14 | Ono Pharmaceutical Co | DERIVATIVES OF AMINOBUTANIC ACID |
| DE19746287A1 (de) | 1997-10-20 | 1999-04-22 | Hoechst Marion Roussel De Gmbh | Substituierte Isochinolin-2-Carbonsäureamide, ihre Herstellung und ihre Verwendung als Arzneimittel |
| CN1297440A (zh) | 1998-03-23 | 2001-05-30 | 阿温蒂斯药物制品公司 | 哌啶基和n－脒基哌啶基衍生物 |
| GB9809213D0 (en) | 1998-04-29 | 1998-07-01 | Glaxo Group Ltd | Pharmaceutical compositions |
| JP4827296B2 (ja) | 1998-06-11 | 2011-11-30 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | デラビルジン錠製剤 |
| US6159379A (en) | 1999-05-04 | 2000-12-12 | Baker Hughes Incorporated | Organic ammonium salts for the removal of water soluble organics in produced water |
| JP2001048786A (ja) | 1999-08-05 | 2001-02-20 | Yamanouchi Pharmaceut Co Ltd | 三環式ヘテロアリール誘導体 |
| US6589758B1 (en) | 2000-05-19 | 2003-07-08 | Amgen Inc. | Crystal of a kinase-ligand complex and methods of use |
| CA2725833A1 (en) * | 2001-01-12 | 2002-07-18 | Sun Pharmaceutical Industries Limited | Spaced drug delivery system |
| US6849718B2 (en) | 2001-03-20 | 2005-02-01 | Dana Farber Cancer Institute, Inc. | Muteins of hypoxia inducible factor alpha and methods of use thereof |
| US6855510B2 (en) | 2001-03-20 | 2005-02-15 | Dana Farber Cancer Institute, Inc. | Pharmaceuticals and methods for treating hypoxia and screening methods therefor |
| AU2002241154A1 (en) | 2001-03-21 | 2002-10-03 | Isis Innovation Ltd. | Assays, methods and means relating to hypoxia inducible factor (hif) hydroxylase |
| SE0101327D0 (sv) | 2001-04-12 | 2001-04-12 | Astrazeneca Ab | New crystalline forms |
| US6566088B1 (en) | 2001-10-04 | 2003-05-20 | Board Of Regents, The University Of Texas System | Prolyl-4-hydroxylases |
| GB0124941D0 (en) | 2001-10-17 | 2001-12-05 | Glaxo Group Ltd | Chemical compounds |
| JP2005524612A (ja) * | 2001-12-06 | 2005-08-18 | ファイブローゲン、インコーポレーテッド | 内因性エリスロポエチン（ｅｐｏ）を増加させる方法 |
| NZ570777A (en) | 2002-05-17 | 2009-04-30 | Celgene Corp | Methods and compositions using selective cytokine inhibitory drugs for treatment and management of cancers and other diseases |
| WO2003101431A1 (en) * | 2002-06-04 | 2003-12-11 | J.B. Chemicals & Pharmaceuticals Ltd. | Pharmaceutical composition for controlled drug delivery system |
| IL166426A0 (en) | 2002-08-29 | 2006-01-15 | Merck & Co Inc | N-biarylmethyl aminocycloalkanecarboxamide derivatives |
| EP2156830A1 (en) | 2002-10-16 | 2010-02-24 | Isis Innovation Limited | Modulators of asparaginyl hydoxylase activity of FIH |
| CA2506799A1 (en) | 2002-11-21 | 2004-06-10 | Eli Lilly And Company | Mixed lineage kinase modulators |
| US7618940B2 (en) | 2002-12-06 | 2009-11-17 | Fibrogen, Inc. | Fat regulation |
| US8124582B2 (en) | 2002-12-06 | 2012-02-28 | Fibrogen, Inc. | Treatment of diabetes |
| US7183287B2 (en) | 2003-04-03 | 2007-02-27 | Pharmacia Corporation | Substituted pyrimidinones |
| CN102718708A (zh) | 2003-06-06 | 2012-10-10 | 菲布罗根有限公司 | 含氮杂芳基化合物及其在增加内源性促红细胞生成素中的用途 |
| US8614204B2 (en) * | 2003-06-06 | 2013-12-24 | Fibrogen, Inc. | Enhanced erythropoiesis and iron metabolism |
| US20060251638A1 (en) | 2003-06-06 | 2006-11-09 | Volkmar Guenzler-Pukall | Cytoprotection through the use of hif hydroxylase inhibitors |
| GB0314129D0 (en) | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
| ES2332798T3 (es) | 2004-05-28 | 2010-02-12 | Fibrogen, Inc. | Ensayo de actividad de la prolil hidroxilasa de hif. |
| TW200609218A (en) | 2004-05-31 | 2006-03-16 | Tanabe Seiyaku Co | Bicyclic compounds |
| CA2573185A1 (en) | 2004-07-14 | 2006-02-23 | Ptc Therapeutics, Inc. | Methods for treating hepatitis c |
| TW200616969A (en) | 2004-09-17 | 2006-06-01 | Tanabe Seiyaku Co | Imidazole compound |
| US20080213404A1 (en) | 2005-02-04 | 2008-09-04 | Johnson Randall S | Hif Modulating Compounds and Methods of Use Thereof |
| DE102005019712A1 (de) | 2005-04-28 | 2006-11-09 | Bayer Healthcare Ag | Dipyridyl-dihydropyrazolone und ihre Verwendung |
| US20060276477A1 (en) | 2005-06-06 | 2006-12-07 | Fibrogen, Inc. | Treatment method for anemia |
| CN101242817B (zh) | 2005-06-15 | 2016-08-31 | 菲布罗根公司 | HIF1α调节剂在治疗癌症中的用途 |
| WO2007033216A2 (en) | 2005-09-12 | 2007-03-22 | Beth Israel Deaconess Medical Center | Methods and compositions for the treatment and diagnosis of diseases characterized by vascular leak, hypotension, or a procoagulant state |
| NZ567188A (en) | 2005-09-12 | 2011-04-29 | Actelion Pharmaceuticals Ltd | Stable pharmaceutical composition comprising a pyrimidine-sulfamide |
| WO2007038571A2 (en) | 2005-09-26 | 2007-04-05 | Smithkline Beecham Corporation | Prolyl hydroxylase antagonists |
| US20090176726A1 (en) | 2005-10-11 | 2009-07-09 | Fisher David E | Methods for treating mitf-related disorders |
| AU2006326662B2 (en) | 2005-12-09 | 2011-07-28 | Amgen Inc. | Quinolone based compounds exhibiting prolyl hydroxylase inhibitory activity, and compositions, and uses thereof |
| MX2008008608A (es) | 2006-01-09 | 2009-03-04 | Btg Int Ltd | Moduladores de factor i inducible por hipoxia y usos relacionados. |
| WO2007082899A1 (en) | 2006-01-17 | 2007-07-26 | Vib Vzw | Inhibitors of prolyl-hydroxylase 1 for the treatment of skeletal muscle degeneration |
| CA2635899A1 (en) | 2006-01-19 | 2007-07-26 | Osi Pharmaceuticals, Inc. | Fused heterobicyclic kinase inhibitors |
| JP4801451B2 (ja) | 2006-01-19 | 2011-10-26 | 株式会社日立ハイテクノロジーズ | 走査電子顕微鏡等に用いる電子銃の制御装置及び制御方法 |
| ITMI20060179A1 (it) | 2006-02-02 | 2007-08-03 | Abiogen Pharma Spa | Procedimento per la risoluzione di miscele racemiche e complesso diastereoisomerico di un agente risolvente e di unantiomero di interesse |
| WO2007101204A1 (en) | 2006-02-27 | 2007-09-07 | Alcon Research, Ltd. | Method of treating glaucoma |
| US7588924B2 (en) | 2006-03-07 | 2009-09-15 | Procter & Gamble Company | Crystal of hypoxia inducible factor 1 alpha prolyl hydroxylase |
| TW200808793A (en) | 2006-03-07 | 2008-02-16 | Smithkline Beecham Corp | Prolyl hydroxylase inhibitors |
| JP2009537558A (ja) | 2006-05-16 | 2009-10-29 | スミスクライン・ビーチャム・コーポレイション | プロリルヒドロキシラーゼ阻害剤 |
| KR100798730B1 (ko) * | 2006-06-12 | 2008-01-29 | 신풍제약주식회사 | 록소프로펜 또는 잘토프로펜 함유 제어방출성 제제 및 그의제조방법 |
| AR061570A1 (es) | 2006-06-23 | 2008-09-03 | Smithkline Beecham Corp | Compuesto de glicina sustituido en el n heteroaromatico composicion farmaceutica que lo comprende, su uso para preparar un medicamento, procedimientos para preparar dicha composicion farmaceutica y para preparar el compuesto |
| CA2563690C (en) | 2006-10-12 | 2014-10-07 | Pharmascience Inc. | Pharmaceutical compositions comprising intra- and extra- granular fractions |
| GB2444904B (en) | 2006-12-05 | 2008-11-05 | Michael Hilary Burke | A Process For The Preparation of an Orally Administrable Unit Dose Tablet |
| CL2008000065A1 (es) | 2007-01-12 | 2008-09-22 | Smithkline Beecham Corp | Compuestos derivados de glicina n-sustituida, inhibidores de hif prolil hidroxilasas; su proceso de preparacion; composicion farmaceutica que comprende a dichos compuestos; y su uso en el tratamiento de la anemia. |
| TW200845991A (en) | 2007-01-12 | 2008-12-01 | Smithkline Beecham Corp | N-substituted glycine derivatives: hydroxylase inhibitors |
| ATE533477T1 (de) | 2007-04-17 | 2011-12-15 | Ratiopharm Gmbh | Pharmazeutische zusammensetzungen enthaltend irbesartan |
| CN101663037A (zh) | 2007-04-18 | 2010-03-03 | 默克公司 | 新的1,8-二氮杂萘化合物 |
| EP2155680B1 (en) | 2007-04-18 | 2013-12-04 | Amgen, Inc | Indanone derivatives that inhibit prolyl hydroxylase |
| EP2150251B9 (en) | 2007-05-04 | 2013-02-27 | Amgen, Inc | Thienopyridine and thiazolopyridine derivatives that inhibit prolyl hydroxylase activity |
| AU2008254270B2 (en) | 2007-05-16 | 2013-06-06 | Merck Sharp & Dohme Corp. | Spiroindalones |
| KR20100016617A (ko) | 2007-05-18 | 2010-02-12 | 바이엘 쉐링 파마 악티엔게젤샤프트 | 과증식성 장애 및 혈관형성 관련 질환의 치료에 유용한 저산소증 유도성 인자 （ｈｉｆ）의 억제제 |
| ES2462416T3 (es) | 2007-08-06 | 2014-05-22 | Senju Pharmaceutical Co., Ltd. | Producto farmacéutico que contiene un inhibidor de la expresión de HIF-1 alfa y HIF-2 alfa |
| TW200908984A (en) | 2007-08-07 | 2009-03-01 | Piramal Life Sciences Ltd | Pyridyl derivatives, their preparation and use |
| CN101815718A (zh) | 2007-08-10 | 2010-08-25 | 克里斯捷诺米有限公司 | 吡啶衍生物及其用法 |
| WO2009035534A2 (en) | 2007-09-07 | 2009-03-19 | The Cleveland Clinic Foundation | Treatment of ischemic eye disease by the systematic pharmaceutical activation of hypoxia inducible factor (hif) |
| WO2009039323A1 (en) | 2007-09-19 | 2009-03-26 | Smithkline Beecham Corporation | Prolyl hydroxylase inhibitors |
| WO2009039321A1 (en) | 2007-09-19 | 2009-03-26 | Smithkline Beecham Corporation | Prolyl hydroxylase inhibitors |
| WO2009043093A1 (en) | 2007-10-04 | 2009-04-09 | Newsouth Innovations Pty Limited | Hif inhibition |
| WO2009049112A1 (en) | 2007-10-10 | 2009-04-16 | Smithkline Beecham Corporation | Prolyl hydroxylase inhibitors |
| WO2009067790A1 (en) | 2007-11-26 | 2009-06-04 | Uti Limited Partnership | STIMULATION OF HYPOXIA INDUCIBLE FACTOR -1 ALPHA (HIF-1α) FOR THE TREATMENT OF CLOSTRIDIUM DIFFICILE ASSOCIATED DISEASE (CDAD), FOR INTESTINAL MOTILITY AND FOR DETECTING INFECTION |
| EP2227770A4 (en) | 2007-11-30 | 2011-11-09 | Glaxosmithkline Llc | PROLYLHYDROXYLASEINHIBITOREN |
| CN101932324A (zh) | 2007-11-30 | 2010-12-29 | 葛兰素史密斯克莱有限责任公司 | 脯氨酰羟化酶抑制剂 |
| US8269008B2 (en) | 2007-12-03 | 2012-09-18 | Fibrogen, Inc. | Oxazolopyridine and isoxazolopyridine derivatives for use in the treatment of HIF-mediated conditions |
| WO2009086044A1 (en) | 2007-12-19 | 2009-07-09 | Smith Kline Beecham Corporation | Prolyl hydroxylase inhibitors |
| WO2009086592A1 (en) | 2008-01-04 | 2009-07-16 | Garvan Institute Of Medical Research | Method of increasing metabolism |
| US8952160B2 (en) | 2008-01-11 | 2015-02-10 | Fibrogen, Inc. | Isothiazole-pyridine derivatives as modulators of HIF (hypoxia inducible factor) activity |
| DK2268618T3 (en) | 2008-03-03 | 2015-08-17 | Novartis Ag | Compounds and compositions as TLR aktivitetsmodulatorer |
| CN102099335A (zh) | 2008-07-23 | 2011-06-15 | 弗·哈夫曼-拉罗切有限公司 | 杂环抗病毒化合物 |
| TW201006473A (en) * | 2008-08-13 | 2010-02-16 | Orient Pharma Co Ltd | Bi-layer medicine tablet containing Zaleplon |
| EP2324006B1 (en) | 2008-09-15 | 2014-08-13 | Kasina Laila Innova Pharmaceuticals Private Ltd. | Anti-cancer drugs and uses relating thereto for metastatic malignant melanoma and other cancers |
| HU230877B1 (hu) * | 2008-09-30 | 2018-11-29 | EGIS Gyógyszergyár NyR | Stabil kombinációs gyógyszerkészítmény |
| CN105037323A (zh) | 2008-11-14 | 2015-11-11 | 菲布罗根有限公司 | 作为hif羟化酶抑制剂的苯并噻喃衍生物 |
| US8137666B2 (en) * | 2008-11-22 | 2012-03-20 | Academia Sinica | Nattokinase for degrading and reducing amyloid fibrils—associated with alzheimer's disease, prion diseases and other amyloidoses |
| PL2732818T3 (pl) | 2009-03-31 | 2017-12-29 | Ligand Pharmaceuticals Inc. | Bifenylosulfonamidowy antagonista receptora endoteliny i angiotensyny II do leczenia stwardnienia kłębków nerkowych |
| BRPI1013432B1 (pt) | 2009-03-31 | 2019-12-17 | Kissei Pharmaceutical | derivado de indolizina e composição farmacêutica |
| HRP20140705T1 (hr) | 2009-07-17 | 2014-09-12 | Japan Tobacco, Inc. | Spoj triazolopiridina i njegovo djelovanje kao inhibitora prolil hidroksilaze i induktora proizvodnje eritropoetina |
| CN102638983B (zh) | 2009-11-06 | 2014-11-26 | 阿尔皮奥治疗学股份有限公司 | 用于治疗结肠炎的组合物和方法 |
| CN103429239A (zh) | 2011-01-13 | 2013-12-04 | 菲布罗根有限公司 | 增加网织红细胞血红蛋白含量的方法 |
| MX2013014310A (es) | 2011-06-06 | 2014-01-23 | Akebia Therapeutics Inc | Compuestos y composiciones para estabilizar el factor-2 alfa inducible por hipoxia como un metodo para tratar el cancer. |
| US20130022974A1 (en) | 2011-06-17 | 2013-01-24 | The Regents Of The University Of Michigan | Dna methylation profiles in cancer |
| KR102029951B1 (ko) | 2011-07-22 | 2019-11-08 | 베이징 베타 파머수티컬 컴퍼니 리미티드 | 프로릴 히드록실라제 억제제로서 화합물의 다형체형, 및 이의 용도 |
| EP2983674A4 (en) | 2013-04-08 | 2017-05-10 | Dennis M. Brown | Therapeutic benefit of suboptimally administered chemical compounds |
| DK3007695T3 (da) * | 2013-06-13 | 2024-03-18 | Akebia Therapeutics Inc | Sammensætninger og fremgangsmåder til behandling af anæmi |
| WO2015023967A2 (en) | 2013-08-16 | 2015-02-19 | Ohio State Innovation Foundation | Compositions and methods for modulating dna methylation |
| SG10202012791TA (en) | 2013-11-15 | 2021-01-28 | Akebia Therapeutics Inc | Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino}acetic acid, compositions, and uses thereof |
| WO2015112831A1 (en) | 2014-01-23 | 2015-07-30 | Akebia Therapeutics, Inc. | Compositions and methods for treating ocular diseases |
| MX2017009417A (es) | 2015-01-23 | 2017-12-07 | Akebia Therapeutics Inc | Formas solidas de acido 2-(5-(3-fluorofenil)-3-hidroxipicolinamido )acetico, composiciones y usos de las mismas. |
| AU2016235534A1 (en) | 2015-03-20 | 2017-10-12 | Akebia Therapeutics, Inc. | Deuterium-enriched hypoxia-inducible factor prolyl hydroxylase enzyme inhibitors |
| PT3277270T (pt) | 2015-04-01 | 2021-12-07 | Akebia Therapeutics Inc | Composições e métodos de tratamento de anemia |
| WO2019028150A1 (en) | 2017-08-01 | 2019-02-07 | Akebia Therapeutics, Inc. | COMPOSITIONS FOR USE IN METHODS OF TREATING HEMOGLOBINOPATHIES |
| MX2021003681A (es) | 2018-10-03 | 2021-08-19 | Akebia Therapeutics Inc | Composiciones y metodos para el tratamiento de desordenes inflamatorios. |
| US11524939B2 (en) * | 2019-11-13 | 2022-12-13 | Akebia Therapeutics, Inc. | Solid forms of {[5-(3-chlorophenyl)-3-hydroxypyridine-2-carbonyl]amino} acetic acid |
-
2014
- 2014-06-04 DK DK14811317.8T patent/DK3007695T3/da active
- 2014-06-04 CA CA3151685A patent/CA3151685A1/en active Pending
- 2014-06-04 KR KR1020167000558A patent/KR102373245B1/ko active Active
- 2014-06-04 LT LTEPPCT/US2014/040889T patent/LT3007695T/lt unknown
- 2014-06-04 SI SI201432066T patent/SI3007695T1/sl unknown
- 2014-06-04 EP EP24156067.1A patent/EP4360706A3/en active Pending
- 2014-06-04 US US14/897,849 patent/US11857543B2/en active Active
- 2014-06-04 KR KR1020227037446A patent/KR102660040B1/ko active Active
- 2014-06-04 MX MX2020006963A patent/MX391198B/es unknown
- 2014-06-04 EP EP14811317.8A patent/EP3007695B1/en active Active
- 2014-06-04 WO PCT/US2014/040889 patent/WO2014200773A2/en not_active Ceased
- 2014-06-04 NZ NZ753905A patent/NZ753905A/en unknown
- 2014-06-04 NZ NZ714963A patent/NZ714963A/en unknown
- 2014-06-04 MX MX2015017229A patent/MX378150B/es unknown
- 2014-06-04 HU HUE14811317A patent/HUE066123T2/hu unknown
- 2014-06-04 RS RS20240271A patent/RS65341B1/sr unknown
- 2014-06-04 BR BR112015031027A patent/BR112015031027A2/pt not_active Application Discontinuation
- 2014-06-04 KR KR1020247012967A patent/KR20240055172A/ko active Pending
- 2014-06-04 JP JP2016519543A patent/JP2016521747A/ja active Pending
- 2014-06-04 RU RU2019134558A patent/RU2019134558A/ru unknown
- 2014-06-04 AU AU2014278543A patent/AU2014278543B2/en active Active
- 2014-06-04 MY MYPI2019003537A patent/MY204336A/en unknown
- 2014-06-04 NZ NZ753904A patent/NZ753904A/en unknown
- 2014-06-04 FI FIEP14811317.8T patent/FI3007695T3/fi active
- 2014-06-04 SM SM20240092T patent/SMT202400092T1/it unknown
- 2014-06-04 KR KR1020217011294A patent/KR102461176B1/ko active Active
- 2014-06-04 ES ES14811317T patent/ES2974273T3/es active Active
- 2014-06-04 HR HRP20240319TT patent/HRP20240319T1/hr unknown
- 2014-06-04 PT PT148113178T patent/PT3007695T/pt unknown
- 2014-06-04 CN CN201480045048.2A patent/CN105451739A/zh active Pending
- 2014-06-04 CA CA2914662A patent/CA2914662C/en active Active
- 2014-06-04 SG SG10201910773VA patent/SG10201910773VA/en unknown
- 2014-06-04 SG SG11201509998WA patent/SG11201509998WA/en unknown
- 2014-06-04 PE PE2020000452A patent/PE20201496A1/es unknown
- 2014-06-04 PL PL14811317.8T patent/PL3007695T3/pl unknown
- 2014-06-04 CN CN202111479723.0A patent/CN114404413A/zh active Pending
- 2014-06-04 RU RU2016100363A patent/RU2705206C2/ru active
- 2014-06-04 CN CN202111479746.1A patent/CN114404414A/zh active Pending
- 2014-06-04 PE PE2015002603A patent/PE20160194A1/es unknown
- 2014-06-13 TW TW103120661A patent/TWI650126B/zh active
- 2014-06-13 TW TW109141639A patent/TWI791177B/zh active
- 2014-06-13 TW TW111149765A patent/TWI856464B/zh active
- 2014-06-13 TW TW113131294A patent/TW202446394A/zh unknown
- 2014-06-13 TW TW107141589A patent/TWI712411B/zh active
-
2015
- 2015-12-07 PH PH12015502738A patent/PH12015502738B1/en unknown
- 2015-12-08 DO DO2015000297A patent/DOP2015000297A/es unknown
- 2015-12-10 IL IL24304715A patent/IL243047B/en active IP Right Grant
- 2015-12-10 ZA ZA2015/09024A patent/ZA201509024B/en unknown
- 2015-12-11 CL CL2015003602A patent/CL2015003602A1/es unknown
- 2015-12-11 MX MX2022003510A patent/MX2022003510A/es unknown
-
2018
- 2018-08-17 CL CL2018002372A patent/CL2018002372A1/es unknown
-
2019
- 2019-05-14 JP JP2019091113A patent/JP6612479B2/ja active Active
- 2019-10-30 JP JP2019197138A patent/JP6937812B2/ja active Active
- 2019-10-31 IL IL270335A patent/IL270335B/en active IP Right Grant
-
2020
- 2020-02-07 AU AU2020200903A patent/AU2020200903B2/en active Active
- 2020-09-17 EC ECSENADI202058592A patent/ECSP20058592A/es unknown
- 2020-10-15 PH PH12020551705A patent/PH12020551705A1/en unknown
-
2021
- 2021-02-23 IL IL281058A patent/IL281058B2/en unknown
- 2021-08-31 JP JP2021140772A patent/JP7328291B2/ja active Active
-
2022
- 2022-01-28 AU AU2022200570A patent/AU2022200570B2/en active Active
-
2023
- 2023-08-03 JP JP2023127201A patent/JP7672455B2/ja active Active
- 2023-11-16 US US18/511,042 patent/US20240335434A1/en active Pending
-
2024
- 2024-03-08 CY CY20241100181T patent/CY1126699T1/el unknown
- 2024-05-29 NO NO2024025C patent/NO2024025I1/no unknown
- 2024-06-03 NL NL301278C patent/NL301278I2/nl unknown
- 2024-06-04 CY CY2024016C patent/CY2024016I1/el unknown
- 2024-06-07 FR FR24C1025C patent/FR24C1025I2/fr active Active
- 2024-06-25 FI FIC20240023C patent/FIC20240023I1/fi unknown
- 2024-06-26 LT LTPA2024521C patent/LTPA2024521I1/lt unknown
- 2024-07-02 HU HUS2400023C patent/HUS2400023I1/hu unknown
- 2024-07-30 AU AU2024205219A patent/AU2024205219A1/en active Pending
-
2025
- 2025-04-22 JP JP2025070412A patent/JP2025114609A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20070299086A1 (en) * | 2006-06-26 | 2007-12-27 | The Procter & Gamble Company | Prolyl hydroxylase inhibitors and methods of use |
| US20120309977A1 (en) * | 2011-06-06 | 2012-12-06 | Akebia Therapeutics Inc. | Process for preparing [(3-hydroxypyridine-2-carbonyl)amino]alkanoic acids, esters and amides |
Non-Patent Citations (3)
| Title |
|---|
| PASQUALETTI P. et al. Circadian rhythm of serum erythropoietin in myelodysplastic syndromes//Eur Rev Med Pharmacol Sci. 2000 Sep-Dec;4(5-6):111-5. PMID: 11710507. * |
| STOHLAWETZ P.J. et al. Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans//Blood. 2000 May 1;95(9):2983-2989 PMID: 10779449. * |
| STOHLAWETZ P.J. et al. Effects of erythropoietin on platelet reactivity and thrombopoiesis in humans//Blood. 2000 May 1;95(9):2983-2989 PMID: 10779449. PASQUALETTI P. et al. Circadian rhythm of serum erythropoietin in myelodysplastic syndromes//Eur Rev Med Pharmacol Sci. 2000 Sep-Dec;4(5-6):111-5. PMID: 11710507. * |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2705206C2 (ru) | Композиции и способы лечения анемии | |
| HK40109871A (en) | Compositions and methods for treating anemia | |
| HK1216844B (en) | Compositions and methods for treating anemia |