JP4541548B2 - 薬剤組成物及び使用方法 - Google Patents
薬剤組成物及び使用方法 Download PDFInfo
- Publication number
- JP4541548B2 JP4541548B2 JP2000554358A JP2000554358A JP4541548B2 JP 4541548 B2 JP4541548 B2 JP 4541548B2 JP 2000554358 A JP2000554358 A JP 2000554358A JP 2000554358 A JP2000554358 A JP 2000554358A JP 4541548 B2 JP4541548 B2 JP 4541548B2
- Authority
- JP
- Japan
- Prior art keywords
- cells
- cddo
- compound
- cox
- disease
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 238000000034 method Methods 0.000 title description 23
- 239000008194 pharmaceutical composition Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 45
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 6
- -1 and R 3 is —OH Chemical group 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 abstract description 16
- 229910052736 halogen Inorganic materials 0.000 abstract description 6
- 150000002367 halogens Chemical class 0.000 abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 5
- 150000002431 hydrogen Chemical group 0.000 abstract description 3
- 150000003573 thiols Chemical class 0.000 abstract description 3
- 210000004027 cell Anatomy 0.000 description 63
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 34
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 33
- 238000004519 manufacturing process Methods 0.000 description 27
- 239000000203 mixture Substances 0.000 description 27
- 108010074328 Interferon-gamma Proteins 0.000 description 21
- 239000002158 endotoxin Substances 0.000 description 21
- 230000000694 effects Effects 0.000 description 19
- 229920006008 lipopolysaccharide Polymers 0.000 description 19
- 102100037850 Interferon gamma Human genes 0.000 description 17
- 201000010099 disease Diseases 0.000 description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 17
- 210000002540 macrophage Anatomy 0.000 description 17
- 208000024827 Alzheimer disease Diseases 0.000 description 16
- MIJYXULNPSFWEK-GTOFXWBISA-N 3beta-hydroxyolean-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C MIJYXULNPSFWEK-GTOFXWBISA-N 0.000 description 15
- 206010028980 Neoplasm Diseases 0.000 description 15
- 201000011510 cancer Diseases 0.000 description 13
- JKLISIRFYWXLQG-UHFFFAOYSA-N Epioleonolsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4CCC3C21C JKLISIRFYWXLQG-UHFFFAOYSA-N 0.000 description 12
- YBRJHZPWOMJYKQ-UHFFFAOYSA-N Oleanolic acid Natural products CC1(C)CC2C3=CCC4C5(C)CCC(O)C(C)(C)C5CCC4(C)C3(C)CCC2(C1)C(=O)O YBRJHZPWOMJYKQ-UHFFFAOYSA-N 0.000 description 12
- MIJYXULNPSFWEK-UHFFFAOYSA-N Oleanolinsaeure Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C(O)=O)CCC(C)(C)CC5C4=CCC3C21C MIJYXULNPSFWEK-UHFFFAOYSA-N 0.000 description 12
- 229940100243 oleanolic acid Drugs 0.000 description 12
- 230000002265 prevention Effects 0.000 description 12
- HZLWUYJLOIAQFC-UHFFFAOYSA-N prosapogenin PS-A Natural products C12CC(C)(C)CCC2(C(O)=O)CCC(C2(CCC3C4(C)C)C)(C)C1=CCC2C3(C)CCC4OC1OCC(O)C(O)C1O HZLWUYJLOIAQFC-UHFFFAOYSA-N 0.000 description 12
- 150000003180 prostaglandins Chemical class 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- 241000699666 Mus <mouse, genus> Species 0.000 description 10
- 208000018737 Parkinson disease Diseases 0.000 description 10
- 230000004069 differentiation Effects 0.000 description 10
- 230000001225 therapeutic effect Effects 0.000 description 10
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N DMSO Substances CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 9
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 229960003957 dexamethasone Drugs 0.000 description 8
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 230000002757 inflammatory effect Effects 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 150000003648 triterpenes Chemical class 0.000 description 8
- WCGUUGGRBIKTOS-GPOJBZKASA-N (3beta)-3-hydroxyurs-12-en-28-oic acid Chemical compound C1C[C@H](O)C(C)(C)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CC[C@@H](C)[C@H](C)[C@H]5C4=CC[C@@H]3[C@]21C WCGUUGGRBIKTOS-GPOJBZKASA-N 0.000 description 7
- 208000005623 Carcinogenesis Diseases 0.000 description 7
- 241000699670 Mus sp. Species 0.000 description 7
- 230000009471 action Effects 0.000 description 7
- 230000036952 cancer formation Effects 0.000 description 7
- 231100000504 carcinogenesis Toxicity 0.000 description 7
- 230000003211 malignant effect Effects 0.000 description 7
- 210000000274 microglia Anatomy 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 7
- 201000006417 multiple sclerosis Diseases 0.000 description 7
- 230000004770 neurodegeneration Effects 0.000 description 7
- 208000015122 neurodegenerative disease Diseases 0.000 description 7
- 206010039073 rheumatoid arthritis Diseases 0.000 description 7
- 229940096998 ursolic acid Drugs 0.000 description 7
- PLSAJKYPRJGMHO-UHFFFAOYSA-N ursolic acid Natural products CC1CCC2(CCC3(C)C(C=CC4C5(C)CCC(O)C(C)(C)C5CCC34C)C2C1C)C(=O)O PLSAJKYPRJGMHO-UHFFFAOYSA-N 0.000 description 7
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 6
- 206010006187 Breast cancer Diseases 0.000 description 6
- 208000026310 Breast neoplasm Diseases 0.000 description 6
- 101150071146 COX2 gene Proteins 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- 102000003777 Interleukin-1 beta Human genes 0.000 description 6
- 108090000193 Interleukin-1 beta Proteins 0.000 description 6
- 108010025020 Nerve Growth Factor Proteins 0.000 description 6
- 102000015336 Nerve Growth Factor Human genes 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000014509 gene expression Effects 0.000 description 6
- 210000004295 hippocampal neuron Anatomy 0.000 description 6
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
- MWUXSHHQAYIFBG-UHFFFAOYSA-N nitrogen oxide Inorganic materials O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 230000002018 overexpression Effects 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 5
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 125000003277 amino group Chemical group 0.000 description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 description 5
- 238000010171 animal model Methods 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 210000001072 colon Anatomy 0.000 description 5
- 239000002270 dispersing agent Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 210000002950 fibroblast Anatomy 0.000 description 5
- 230000012010 growth Effects 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 230000005764 inhibitory process Effects 0.000 description 5
- 208000032839 leukemia Diseases 0.000 description 5
- 238000013518 transcription Methods 0.000 description 5
- 230000035897 transcription Effects 0.000 description 5
- 238000013519 translation Methods 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 4
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 102000000587 Glycerolphosphate Dehydrogenase Human genes 0.000 description 4
- 108010041921 Glycerolphosphate Dehydrogenase Proteins 0.000 description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 4
- 102000008070 Interferon-gamma Human genes 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical group C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 4
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 4
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 230000000112 colonic effect Effects 0.000 description 4
- 125000000753 cycloalkyl group Chemical group 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 229940011871 estrogen Drugs 0.000 description 4
- 239000000262 estrogen Substances 0.000 description 4
- 230000001939 inductive effect Effects 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 239000004615 ingredient Substances 0.000 description 4
- 229960003130 interferon gamma Drugs 0.000 description 4
- 210000002241 neurite Anatomy 0.000 description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 4
- 108090000623 proteins and genes Proteins 0.000 description 4
- 230000001629 suppression Effects 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- 210000004881 tumor cell Anatomy 0.000 description 4
- 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 3
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 3
- 0 CC(*CN*)C=C Chemical compound CC(*CN*)C=C 0.000 description 3
- 102000004127 Cytokines Human genes 0.000 description 3
- 108090000695 Cytokines Proteins 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 101150109636 Inos gene Proteins 0.000 description 3
- 102000000589 Interleukin-1 Human genes 0.000 description 3
- 108010002352 Interleukin-1 Proteins 0.000 description 3
- 108010052989 Naphthol AS D Esterase Proteins 0.000 description 3
- 238000000636 Northern blotting Methods 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 3
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 125000005157 alkyl carboxy group Chemical group 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- 238000002512 chemotherapy Methods 0.000 description 3
- 229940125773 compound 10 Drugs 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Substances N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000002502 liposome Substances 0.000 description 3
- 230000036210 malignancy Effects 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 230000007246 mechanism Effects 0.000 description 3
- 244000005700 microbiome Species 0.000 description 3
- 210000001616 monocyte Anatomy 0.000 description 3
- 208000025113 myeloid leukemia Diseases 0.000 description 3
- 230000000626 neurodegenerative effect Effects 0.000 description 3
- 230000014511 neuron projection development Effects 0.000 description 3
- 230000008506 pathogenesis Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000001105 regulatory effect Effects 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 description 2
- YYGNTYWPHWGJRM-UHFFFAOYSA-N (6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene Chemical compound CC(C)=CCCC(C)=CCCC(C)=CCCC=C(C)CCC=C(C)CCC=C(C)C YYGNTYWPHWGJRM-UHFFFAOYSA-N 0.000 description 2
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 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
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 2
- 241000283690 Bos taurus Species 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- 241000283707 Capra Species 0.000 description 2
- 229940126657 Compound 17 Drugs 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 229940125614 Noora Drugs 0.000 description 2
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical group C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 2
- 241001494479 Pecora Species 0.000 description 2
- 244000046052 Phaseolus vulgaris Species 0.000 description 2
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 2
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Chemical group C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 2
- 206010060862 Prostate cancer Diseases 0.000 description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical group C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 2
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 2
- 102000034527 Retinoid X Receptors Human genes 0.000 description 2
- 108010038912 Retinoid X Receptors Proteins 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- BHEOSNUKNHRBNM-UHFFFAOYSA-N Tetramethylsqualene Natural products CC(=C)C(C)CCC(=C)C(C)CCC(C)=CCCC=C(C)CCC(C)C(=C)CCC(C)C(C)=C BHEOSNUKNHRBNM-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 2
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 2
- WREOTYWODABZMH-DTZQCDIJSA-N [[(2r,3s,4r,5r)-3,4-dihydroxy-5-[2-oxo-4-(2-phenylethoxyamino)pyrimidin-1-yl]oxolan-2-yl]methoxy-hydroxyphosphoryl] phosphono hydrogen phosphate Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N(C=C\1)C(=O)NC/1=N\OCCC1=CC=CC=C1 WREOTYWODABZMH-DTZQCDIJSA-N 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 229940114078 arachidonate Drugs 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 210000004958 brain cell Anatomy 0.000 description 2
- 125000001246 bromo group Chemical group Br* 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 230000004663 cell proliferation Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000004736 colon carcinogenesis Effects 0.000 description 2
- 208000029742 colonic neoplasm Diseases 0.000 description 2
- 229940126543 compound 14 Drugs 0.000 description 2
- 229940125758 compound 15 Drugs 0.000 description 2
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 description 2
- 239000002612 dispersion medium Substances 0.000 description 2
- PRAKJMSDJKAYCZ-UHFFFAOYSA-N dodecahydrosqualene Natural products CC(C)CCCC(C)CCCC(C)CCCCC(C)CCCC(C)CCCC(C)C PRAKJMSDJKAYCZ-UHFFFAOYSA-N 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 125000006575 electron-withdrawing group Chemical group 0.000 description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 102000006602 glyceraldehyde-3-phosphate dehydrogenase Human genes 0.000 description 2
- 108020004445 glyceraldehyde-3-phosphate dehydrogenase Proteins 0.000 description 2
- 239000004519 grease Substances 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 125000001188 haloalkyl group Chemical group 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 208000027866 inflammatory disease Diseases 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 2
- 108020004999 messenger RNA Proteins 0.000 description 2
- 210000000651 myofibroblast Anatomy 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 210000002569 neuron Anatomy 0.000 description 2
- 230000004031 neuronal differentiation Effects 0.000 description 2
- 230000007514 neuronal growth Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 244000052769 pathogen Species 0.000 description 2
- 210000003024 peritoneal macrophage Anatomy 0.000 description 2
- WJCXADMLESSGRI-UHFFFAOYSA-N phenyl selenohypochlorite Chemical compound Cl[Se]C1=CC=CC=C1 WJCXADMLESSGRI-UHFFFAOYSA-N 0.000 description 2
- 208000028591 pheochromocytoma Diseases 0.000 description 2
- 238000007747 plating Methods 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 210000002307 prostate Anatomy 0.000 description 2
- 210000005267 prostate cell Anatomy 0.000 description 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000009331 sowing Methods 0.000 description 2
- 229940031439 squalene Drugs 0.000 description 2
- TUHBEKDERLKLEC-UHFFFAOYSA-N squalene Natural products CC(=CCCC(=CCCC(=CCCC=C(/C)CCC=C(/C)CC=C(C)C)C)C)C TUHBEKDERLKLEC-UHFFFAOYSA-N 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 2
- 229930192474 thiophene Chemical group 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 150000003852 triazoles Chemical group 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- ONBQEOIKXPHGMB-VBSBHUPXSA-N 1-[2-[(2s,3r,4s,5r)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-4,6-dihydroxyphenyl]-3-(4-hydroxyphenyl)propan-1-one Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1OC1=CC(O)=CC(O)=C1C(=O)CCC1=CC=C(O)C=C1 ONBQEOIKXPHGMB-VBSBHUPXSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 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
- DPEUWKZJZIPZKE-OFANTOPUSA-N 330936-69-1 Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)O)NC(=O)CNC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@@H](N)CCSC)C1=CC=CC=C1 DPEUWKZJZIPZKE-OFANTOPUSA-N 0.000 description 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- DGAKHGXRMXWHBX-ONEGZZNKSA-N Azoxymethane Chemical compound C\N=[N+](/C)[O-] DGAKHGXRMXWHBX-ONEGZZNKSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010005949 Bone cancer Diseases 0.000 description 1
- 208000018084 Bone neoplasm Diseases 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 208000003174 Brain Neoplasms Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000031229 Cardiomyopathies Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000143940 Colias Species 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 108020004414 DNA Proteins 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000003676 Glucocorticoid Receptors Human genes 0.000 description 1
- 108090000079 Glucocorticoid Receptors Proteins 0.000 description 1
- 229940123037 Glucocorticoid antagonist Drugs 0.000 description 1
- 101000988651 Homo sapiens Humanin-like 1 Proteins 0.000 description 1
- 101000998969 Homo sapiens Inositol-3-phosphate synthase 1 Proteins 0.000 description 1
- 102100036881 Inositol-3-phosphate synthase 1 Human genes 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 208000032177 Intestinal Polyps Diseases 0.000 description 1
- 238000006809 Jones oxidation reaction Methods 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
- 238000000134 MTT assay Methods 0.000 description 1
- 231100000002 MTT assay Toxicity 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 1
- 229910003827 NRaRb Inorganic materials 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 102000011779 Nitric Oxide Synthase Type II Human genes 0.000 description 1
- 108010076864 Nitric Oxide Synthase Type II Proteins 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 208000037062 Polyps Diseases 0.000 description 1
- 102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 description 1
- 108050003243 Prostaglandin G/H synthase 1 Proteins 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 239000006146 Roswell Park Memorial Institute medium Substances 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical group [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 239000003070 absorption delaying agent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 210000001642 activated microglia Anatomy 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000004442 acylamino group Chemical group 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 description 1
- 125000004947 alkyl aryl amino group Chemical group 0.000 description 1
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical group C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000003217 anti-cancerogenic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 125000004658 aryl carbonyl amino group Chemical group 0.000 description 1
- 125000005199 aryl carbonyloxy group Chemical group 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000005200 aryloxy carbonyloxy group Chemical group 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 210000001130 astrocyte Anatomy 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 150000001555 benzenes Chemical class 0.000 description 1
- 210000003008 brain-resident macrophage Anatomy 0.000 description 1
- 210000000069 breast epithelial cell Anatomy 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical group [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 231100000357 carcinogen Toxicity 0.000 description 1
- 231100000315 carcinogenic Toxicity 0.000 description 1
- 239000003183 carcinogenic agent Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 239000006143 cell culture medium Substances 0.000 description 1
- 230000010261 cell growth Effects 0.000 description 1
- 239000013592 cell lysate Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 208000029664 classic familial adenomatous polyposis Diseases 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940126142 compound 16 Drugs 0.000 description 1
- 238000010276 construction Methods 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 230000034994 death Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 125000004986 diarylamino group Chemical group 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 229960002986 dinoprostone Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 210000002257 embryonic structure Anatomy 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 231100000284 endotoxic Toxicity 0.000 description 1
- 230000002346 endotoxic effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012894 fetal calf serum Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 239000003635 glucocorticoid antagonist Substances 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 102000011854 humanin Human genes 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 230000008076 immune mechanism Effects 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 230000000984 immunochemical effect Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000003960 inflammatory cascade Effects 0.000 description 1
- 230000004968 inflammatory condition Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 230000013011 mating Effects 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
- 230000003505 mutagenic effect Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 230000017095 negative regulation of cell growth Effects 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 1
- 150000002825 nitriles Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 238000007899 nucleic acid hybridization Methods 0.000 description 1
- 229940049964 oleate Drugs 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 210000004248 oligodendroglia Anatomy 0.000 description 1
- 238000002515 oligonucleotide synthesis Methods 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 230000004792 oxidative damage Effects 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000008458 response to injury Effects 0.000 description 1
- 150000004492 retinoid derivatives Chemical class 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000011146 sterile filtration Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 210000002536 stromal cell Anatomy 0.000 description 1
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical group [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229940071127 thioglycolate Drugs 0.000 description 1
- CWERGRDVMFNCDR-UHFFFAOYSA-M thioglycolate(1-) Chemical compound [O-]C(=O)CS CWERGRDVMFNCDR-UHFFFAOYSA-M 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/47—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of rings being part of condensed ring systems
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
-
- 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
- A61K31/275—Nitriles; Isonitriles
-
- 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
- A61K31/275—Nitriles; Isonitriles
- A61K31/277—Nitriles; Isonitriles having a ring, e.g. verapamil
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- 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
- A61P9/00—Drugs for disorders of the cardiovascular system
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9005398P | 1998-06-19 | 1998-06-19 | |
| US60/090,053 | 1998-06-19 | ||
| US09/335,003 US6326507B1 (en) | 1998-06-19 | 1999-06-17 | Therapeutic compounds and methods of use |
| US09/335,003 | 1999-06-17 | ||
| PCT/US1999/013635 WO1999065478A1 (en) | 1998-06-19 | 1999-06-18 | Therapeutic compositions and methods of use |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009136739A Division JP5210971B2 (ja) | 1998-06-19 | 2009-06-05 | 薬剤組成物及び使用方法 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002530272A JP2002530272A (ja) | 2002-09-17 |
| JP2002530272A5 JP2002530272A5 (enExample) | 2009-07-30 |
| JP4541548B2 true JP4541548B2 (ja) | 2010-09-08 |
Family
ID=22221055
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000554358A Expired - Lifetime JP4541548B2 (ja) | 1998-06-19 | 1999-06-18 | 薬剤組成物及び使用方法 |
| JP2009136739A Expired - Lifetime JP5210971B2 (ja) | 1998-06-19 | 2009-06-05 | 薬剤組成物及び使用方法 |
| JP2012102499A Withdrawn JP2012144574A (ja) | 1998-06-19 | 2012-04-27 | 薬剤組成物及び使用方法 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009136739A Expired - Lifetime JP5210971B2 (ja) | 1998-06-19 | 2009-06-05 | 薬剤組成物及び使用方法 |
| JP2012102499A Withdrawn JP2012144574A (ja) | 1998-06-19 | 2012-04-27 | 薬剤組成物及び使用方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (7) | US6326507B1 (enExample) |
| EP (2) | EP1089724B1 (enExample) |
| JP (3) | JP4541548B2 (enExample) |
| AT (1) | ATE430563T1 (enExample) |
| CA (1) | CA2335505C (enExample) |
| CY (1) | CY1109256T1 (enExample) |
| DK (1) | DK1089724T3 (enExample) |
| ES (1) | ES2324966T3 (enExample) |
| PT (1) | PT1089724E (enExample) |
| WO (1) | WO1999065478A1 (enExample) |
Families Citing this family (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040072138A1 (en) * | 1997-11-25 | 2004-04-15 | Medical University Of South Carolina | Attenuation of ischemia/reperfusion injury |
| US20080275104A1 (en) * | 1997-11-25 | 2008-11-06 | Musc Foundation For Research Development | Methods of treating juvenile type 1 diabetes mellitus |
| WO1999026657A1 (en) * | 1997-11-25 | 1999-06-03 | Musc Foundation For Research Development | Inhibitors of nitric oxide synthase |
| US6326507B1 (en) | 1998-06-19 | 2001-12-04 | Trustees Of Dartmouth College | Therapeutic compounds and methods of use |
| WO2001054688A1 (en) * | 2000-01-28 | 2001-08-02 | Merck & Co., Inc. | Treatment or prevention of prostate cancer with a cox-2 selective inhibiting drug |
| WO2002047611A2 (en) * | 2000-11-28 | 2002-06-20 | Board Of Regents, The University Of Texas System | Cddo-compounds and combination therapies thereof |
| US7435755B2 (en) * | 2000-11-28 | 2008-10-14 | The Trustees Of Dartmouth College | CDDO-compounds and combination therapies thereof |
| US6777004B1 (en) * | 2001-03-30 | 2004-08-17 | Council Of Scientific & Industrial Research | Composition containing novel compound corniculatonin having antifungi properties and a process for preparing the same |
| KR100464063B1 (ko) * | 2001-11-21 | 2005-01-06 | 한국생명공학연구원 | 세포사멸 유도작용을 갖는 트리테르펜 화합물 |
| AU2003235676A1 (en) * | 2002-01-15 | 2003-07-30 | Trustees Of Dartmouth College | Tricyclic-bis-enone derivatives and methods of use thereof |
| CA2484989A1 (en) * | 2002-05-02 | 2003-11-27 | The Washington University | Methods and compositions for treating t cell mediated inflammatory/autoimmune diseases and disorders in subjects having a glucocorticoid regulation deficiency |
| CA2485565A1 (en) * | 2002-05-13 | 2004-08-05 | Trustees Of Dartmouth College | Inhibitors and methods of use thereof |
| WO2005034958A1 (en) * | 2003-10-10 | 2005-04-21 | Sk Chemicals, Co., Ltd. | Triterpene compounds which are effective on improvement of brain function |
| WO2005042002A2 (en) * | 2003-10-30 | 2005-05-12 | Entelos, Inc. | Treatment of rhematoid arthritis with flip antagonists |
| US7551346B2 (en) * | 2003-11-05 | 2009-06-23 | E Ink Corporation | Electro-optic displays, and materials for use therein |
| WO2005063275A1 (en) * | 2003-12-23 | 2005-07-14 | Musc Foundaton For Research Development | Methods and compositions for the prevention and treatment of inflammatory diseases or conditions |
| US7638331B2 (en) | 2004-01-02 | 2009-12-29 | The Administration of the Tulane Rducation Fund | Directed apoptosis in COX-2 overexpressing cancer cells through expression targeted gene delivery |
| US20080318931A1 (en) * | 2004-07-08 | 2008-12-25 | Moshe Arkin | Treatment of Disorders and Diseases of the Colon |
| ES2397085T3 (es) * | 2005-03-08 | 2013-03-04 | Mitsui Norin Co., Ltd | Procedimientos y combinaciones de polifenol-coxib |
| US20100190735A1 (en) * | 2006-03-28 | 2010-07-29 | Myrex Pharmaceuticals Inc. | Mouthwash and Method of Using Same for the Treatment of Mucositis or Stomatitis |
| US8299046B2 (en) * | 2006-11-17 | 2012-10-30 | Trustees Of Dartmouth College | Synthetic triterpenoids and tricyclic-bis-enones for use in stimulating bone and cartilage growth |
| EP2094651A1 (en) * | 2006-11-17 | 2009-09-02 | Trustees Of Dartmouth College | Synthesis and biological activities of new tricyclic-bis-enones (tbes) |
| US8921340B2 (en) | 2006-11-17 | 2014-12-30 | Trustees Of Dartmouth College | Methods for using synthetic triterpenoids in the treatment of bone or cartilage diseases or conditions |
| WO2008112887A1 (en) * | 2007-03-13 | 2008-09-18 | Musc Foundation For Research Development | Methods of treating juvenile type 1 diabetes mellitus |
| US20090048205A1 (en) * | 2007-08-15 | 2009-02-19 | Colin Meyer | Combination therapy with synthetic triterpenoids and gemcitabine |
| US8088824B2 (en) | 2007-08-15 | 2012-01-03 | Reata Pharmaceuticals Inc. | Forms of CDDO methyl ester |
| US7879369B2 (en) | 2007-09-18 | 2011-02-01 | Selvamedica, Llc | Combretum laurifolium Mart. extract and methods of extracting and using such extract |
| US9012439B2 (en) * | 2007-10-29 | 2015-04-21 | University Of Rochester | Use of electrophilic compounds for inducing platelet production or maintaining platelet function |
| ME03529B (me) | 2008-01-11 | 2020-04-20 | Reata Pharmaceuticals Inc | Sintetički triterpenoidi i metode njihove upotrebe u tretmanu bolesti |
| ES2326065B1 (es) * | 2008-03-28 | 2010-07-08 | Consejo Superior De Investigaciones Cientificas (Csic) | Utilizacion de un triterpeno pentaciclico para la preparacion de una composicion farmaceutica destinada al tratamiento de la esclerosis multiple. |
| EP2279197B1 (en) | 2008-04-18 | 2014-11-05 | Reata Pharmaceuticals, Inc. | Antioxidant inflammation modulators: oleanolic acid derivatives with saturation in the c-ring |
| WO2009146216A2 (en) | 2008-04-18 | 2009-12-03 | Reata Pharmaceuticals. Inc. | Antioxidant inflammation modulators: novel derivatives of oleanolic acid |
| SI2271658T1 (sl) * | 2008-04-18 | 2017-03-31 | Reata Pharmaceuticals, Inc. | Antioksidantni modulatorji vnetja: C-17 homologirani derivati oleanolne kisline |
| CN102083442B (zh) | 2008-04-18 | 2014-08-13 | 里亚塔医药公司 | 抗氧化剂炎症调节剂：在c-17具有氨基和其它修饰的齐墩果酸衍生物 |
| CA2721665C (en) | 2008-04-18 | 2017-01-24 | Reata Pharmaceuticals, Inc. | Compounds including an anti-inflammatory pharmacore and methods of use |
| ES2449396T3 (es) | 2008-07-22 | 2014-03-19 | Trustees Of Dartmouth College | Cianoenonas monocíclicas y métodos de uso de las mismas |
| HUE035013T2 (en) | 2009-02-13 | 2018-05-02 | Reata Pharmaceuticals Inc | Delayed release, oral dosage compositions that contain amorphous cddo-me |
| JP5687690B2 (ja) * | 2009-04-30 | 2015-03-18 | サノフィ−アベンティス・ドイチュラント・ゲゼルシャフト・ミット・ベシュレンクテル・ハフツング | 針リムーバ及び針を除去する方法 |
| EP2558105B1 (en) | 2010-04-12 | 2019-11-20 | Reata Pharmaceuticals, Inc. | Bardoxolone methyl for the treatment of obesity |
| KR101220782B1 (ko) | 2010-09-14 | 2013-01-09 | 제주대학교 산학협력단 | 신규 트리테르페노이드 및 이의 용도 |
| CA2822071C (en) | 2010-12-17 | 2019-07-16 | Reata Pharmaceuticals, Inc. | Pyrazolyl and pyrimidinyl tricyclic enones as antioxidant inflammation modulators |
| HUE044081T2 (hu) | 2011-03-11 | 2019-09-30 | Reata Pharmaceuticals Inc | C4 Monometil-triterpenoid-származékok, és módszerek azok alkalmazására |
| GB201120860D0 (en) | 2011-12-05 | 2012-01-18 | Cambridge Entpr Ltd | Cancer immunotherapy |
| BR112014026640B1 (pt) | 2012-04-27 | 2021-05-18 | Reata Pharmaceuticals, Inc | compostos derivados de 2,2-difluoropropionamida de metil bardoxolona, formas polimórficas, composição farmacêutica, e uso dos mesmos |
| US8921419B2 (en) | 2012-05-08 | 2014-12-30 | Trustees Of Dartmouth College | Triterpenoids and compositions containing the same |
| US8981144B2 (en) | 2012-05-08 | 2015-03-17 | Trustees Of Dartmouth College | Method for synthesizing 2-cyano-3,12-dioxoolean-1, 9(11)-dien-28-oic acid methyl ester and derivatives thereof |
| US9556222B2 (en) | 2012-06-15 | 2017-01-31 | Reata Pharmaceuticals, Inc. | A-ring epoxidized triterpenoid-based anti-inflammation modulators and methods of use thereof |
| US8791067B2 (en) | 2012-07-24 | 2014-07-29 | Morehouse School Of Medicine | Method for treating malaria |
| JP2015527407A (ja) * | 2012-09-10 | 2015-09-17 | アッヴィ・インコーポレイテッド | グリチルレチン酸誘導体およびその使用方法 |
| JP6272870B2 (ja) * | 2012-09-10 | 2018-01-31 | リアタ ファーマシューティカルズ インコーポレイテッド | オレアノール酸のｃ１７−ヘテロアリール誘導体ならびにその使用方法 |
| WO2014040073A1 (en) | 2012-09-10 | 2014-03-13 | Reata Pharmaceuticals, Inc. | C13-hydroxy derivatives of oleanolic acid and methods of use thereof |
| US9512094B2 (en) | 2012-09-10 | 2016-12-06 | Reata Pharmaceuticals, Inc. | C17-heteroaryl derivatives of oleanolic acid and methods of use thereof |
| RS59194B1 (sr) | 2012-09-10 | 2019-10-31 | Reata Pharmaceuticals Inc | C17-alkandiilni i alkendiilni derivati oleanolne kiseline i metode za njihovu upotrebu |
| CN102887936A (zh) * | 2012-10-24 | 2013-01-23 | 苏州晶云药物科技有限公司 | 2-氰基-3,12-二氧代齐墩果-1,9(11)-二烯-28-酸甲酯晶型 |
| WO2014148455A1 (ja) | 2013-03-19 | 2014-09-25 | 第一三共株式会社 | テルペノイド誘導体 |
| AR096046A1 (es) | 2013-04-24 | 2015-12-02 | Abbvie Inc | Derivados de 2,2-difluoropropanamida de metil bardoxolona, formas polimórficas y métodos de uso |
| US9290455B2 (en) | 2014-02-11 | 2016-03-22 | Trustees Of Dartmouth College | CDDO-Me amino acid conjugates and methods of use |
| WO2016033132A1 (en) | 2014-08-26 | 2016-03-03 | Trustees Of Dartmouth College | Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole |
| US10189791B2 (en) | 2014-08-26 | 2019-01-29 | Trustees Of Dartmouth College | Pyridyl analogs of 1-(2-cyano-3,12-dioxooleana-1,9(11)dien-28-oyl) imidazole |
| ES2770772T3 (es) | 2014-09-10 | 2020-07-03 | Daiichi Sankyo Co Ltd | Composición farmacéutica de liberación sostenida para el tratamiento y prevención de enfermedades oculares |
| US11059792B2 (en) | 2015-02-12 | 2021-07-13 | Reata Pharmaceuticals, Inc. | Imidazolyl tricyclic enones as antioxidant inflammation modulators |
| BR112018005861B1 (pt) | 2015-09-23 | 2022-11-22 | Reata Pharmaceuticals, Inc | Compostos derivados de ácido oleanólico modificado com c4 para a inibição de il-17, composição farmacêutica e usos terapêuticos dos ditos compostos |
| CA3042123A1 (en) | 2016-11-08 | 2018-05-17 | Reata Pharmaceuticals, Inc. | Methods of treating alport syndrome using bardoxolone methyl or analogs thereof |
| TWI831738B (zh) | 2016-12-16 | 2024-02-11 | 美商瑞塔醫藥有限責任公司 | 用於抑制ＲＯＲγ及其他用途的嘧啶三環烯酮衍生物 |
| CN110536685A (zh) * | 2016-12-23 | 2019-12-03 | 昆士兰大学 | Sox18蛋白活性的抑制剂用于治疗血管生成相关疾病和/或淋巴管生成相关疾病 |
| US11427533B2 (en) | 2017-07-13 | 2022-08-30 | Pliva Hrvatska D.O.O. | Crystalline polymorphs of bardoxolone methyl |
| US11993574B2 (en) | 2018-06-15 | 2024-05-28 | Reata Pharmaceuticals, Inc | Pyrazole and imidazole compounds for inhibition of IL-17 and RORgamma |
| WO2019246461A1 (en) | 2018-06-20 | 2019-12-26 | Reata Pharmaceuticals, Inc. | Cysteine-dependent inverse agonists of nuclear receptors ror-gamma/ror-gamma-t and methods of treating diseases or disorders therewith |
| TW202038918A (zh) | 2018-11-27 | 2020-11-01 | 日商協和麒麟股份有限公司 | 醫藥組合物 |
| CN120248001A (zh) | 2019-07-19 | 2025-07-04 | 里亚塔医药公司 | C17极性的-取代的杂芳族合成三萜类化合物及其使用方法 |
| AU2021397631A1 (en) | 2020-12-11 | 2023-07-20 | Reata Pharmaceuticals Holdings, LLC | Synthetic triterpenoids for use in therapy |
| TW202340204A (zh) | 2022-01-07 | 2023-10-16 | 日商中外製藥股份有限公司 | 具有Nrf2活化作用的含氮雜環化合物 |
| WO2025029691A1 (en) * | 2023-07-28 | 2025-02-06 | Reata Pharmaceuticals Holdings, LLC | Methods for producing triterpenoid derivatives |
Family Cites Families (60)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4395423A (en) | 1978-10-10 | 1983-07-26 | Sterling Drug Inc. | Polycyclic cyanoketones |
| NZ191586A (en) * | 1978-10-10 | 1981-10-19 | Sterling Drug Inc | Cyanoketones derived from glycyrrhetinic acid and pharmaceutical compositions |
| US4526988A (en) | 1983-03-10 | 1985-07-02 | Eli Lilly And Company | Difluoro antivirals and intermediate therefor |
| ATE92499T1 (de) | 1984-12-04 | 1993-08-15 | Lilly Co Eli | Tumorbehandlung bei saeugetieren. |
| US4683195A (en) | 1986-01-30 | 1987-07-28 | Cetus Corporation | Process for amplifying, detecting, and/or-cloning nucleic acid sequences |
| US5013649A (en) | 1986-07-01 | 1991-05-07 | Genetics Institute, Inc. | DNA sequences encoding osteoinductive products |
| PT86377B (pt) | 1986-12-24 | 1990-11-20 | Lilly Co Eli | Processo para a preparacao de conjugados de imunoglobulinas com um difluoronucleosideo acilado |
| ES2075040T3 (es) | 1988-02-16 | 1995-10-01 | Lilly Co Eli | 2',3'-dideoxi-2',2'-difluoronucleosidos. |
| US5064823A (en) | 1988-08-24 | 1991-11-12 | Research Triangle Institute | Pentacyclic triterpenoid compounds as topoisomerase inhibitors or cell differentiation inducers |
| CA2004695C (en) | 1988-12-12 | 1999-08-10 | Rosanne Bonjouklian | Phospholipid nucleosides |
| WO1991015498A2 (en) | 1990-04-04 | 1991-10-17 | Nycomed Imaging As | Nucleoside derivatives |
| EP0526642B1 (en) | 1991-01-29 | 1998-04-01 | Shionogi Seiyaku Kabushiki Kaisha | Triterpene derivative |
| SE502569C2 (sv) * | 1991-05-31 | 1995-11-13 | British Tech Group | Användning av en immunologiskt inert matris av en sterol och saponiner som kan bilda sfäriska nanopartiklar med snäv storleksfördelning som läkemedelsbärare, partiklar, komposition samt kit |
| US5606048A (en) | 1992-06-22 | 1997-02-25 | Eli Lilly And Company | Stereoselective glycosylation process for preparing 2'-Deoxy-2', 2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| UA41261C2 (uk) | 1992-06-22 | 2001-09-17 | Елі Ліллі Енд Компані | Спосіб одержання збагачених бета-аномером нуклеозидів |
| US5401838A (en) | 1992-06-22 | 1995-03-28 | Eli Lilly And Company | Stereoselective fusion glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| YU43193A (sh) | 1992-06-22 | 1997-01-08 | Eli Lilly And Company | 2'-deoksi-2',2'-difluoro(4-supstituisani)pirimidinski nukleozidi antivirusnog i antikancerogenog dejstva i međuproizvodi |
| US5426183A (en) | 1992-06-22 | 1995-06-20 | Eli Lilly And Company | Catalytic stereoselective glycosylation process for preparing 2'-deoxy-2',2'-difluoronucleosides and 2'-deoxy-2'-fluoronucleosides |
| DE4308042C2 (de) | 1993-03-13 | 2000-10-12 | Alstom Energy Syst Gmbh | Wälzmühle |
| US6025395A (en) | 1994-04-15 | 2000-02-15 | Duke University | Method of preventing or delaying the onset and progression of Alzheimer's disease and related disorders |
| US5972703A (en) | 1994-08-12 | 1999-10-26 | The Regents Of The University Of Michigan | Bone precursor cells: compositions and methods |
| US5521294A (en) | 1995-01-18 | 1996-05-28 | Eli Lilly And Company | 2,2-difluoro-3-carbamoyl ribose sulfonate compounds and process for the preparation of beta nucleosides |
| PT909184E (pt) | 1996-07-03 | 2004-02-27 | Upjohn Co | Libertacao de farmaco para um alvo utilizando derivados de sulfonamida |
| WO1998032762A1 (en) | 1997-01-24 | 1998-07-30 | Norsk Hydro Asa | Gemcitabine derivatives |
| US20050276836A1 (en) | 1997-06-11 | 2005-12-15 | Michelle Wilson | Coated vaginal devices for vaginal delivery of therapeutically effective and/or health-promoting agents |
| US5965119A (en) | 1997-12-30 | 1999-10-12 | Enzon, Inc. | Trialkyl-lock-facilitated polymeric prodrugs of amino-containing bioactive agents |
| US6326507B1 (en) | 1998-06-19 | 2001-12-04 | Trustees Of Dartmouth College | Therapeutic compounds and methods of use |
| US6485756B1 (en) * | 1999-04-06 | 2002-11-26 | Collaborative Technologies, Inc. | Stable, homogeneous natural product extracts containing polar and apolar fractions |
| CN1361760A (zh) | 1999-05-14 | 2002-07-31 | 尼瑞斯药品公司 | 新的白介素－1和肿瘤坏死因子－α调节剂、所述调节剂的合成以及使用所述调节剂的方法 |
| CA2341263C (en) | 1999-06-25 | 2006-08-01 | Roche Diagnostics Corporation | Enzyme inhibition immunoassay |
| WO2002003996A1 (en) | 2000-07-12 | 2002-01-17 | RAJKUMAR, Sujatha | Use of dammarane-type tritepenoid saporins |
| US7435755B2 (en) | 2000-11-28 | 2008-10-14 | The Trustees Of Dartmouth College | CDDO-compounds and combination therapies thereof |
| WO2002047611A2 (en) | 2000-11-28 | 2002-06-20 | Board Of Regents, The University Of Texas System | Cddo-compounds and combination therapies thereof |
| JP2005514359A (ja) | 2001-11-23 | 2005-05-19 | 中外製薬株式会社 | 腫瘍を標的とする酵素の同定法 |
| AU2003235676A1 (en) | 2002-01-15 | 2003-07-30 | Trustees Of Dartmouth College | Tricyclic-bis-enone derivatives and methods of use thereof |
| CA2485565A1 (en) | 2002-05-13 | 2004-08-05 | Trustees Of Dartmouth College | Inhibitors and methods of use thereof |
| EP1567169A4 (en) | 2002-11-04 | 2009-10-21 | Xenoport Inc | GEMCITABINE PROMOTERS, THEIR PHARMACEUTICAL COMPOSITIONS AND USES THEREOF |
| WO2005042002A2 (en) | 2003-10-30 | 2005-05-12 | Entelos, Inc. | Treatment of rhematoid arthritis with flip antagonists |
| US8288439B2 (en) | 2003-11-04 | 2012-10-16 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Methods and compositions for the inhibition of HIV-1 replication |
| JP5087400B2 (ja) | 2004-09-07 | 2012-12-05 | パシフィック アロー リミテッド | アンゲロイル基を有する抗腫瘍化合物 |
| EP1959969A2 (en) | 2005-07-01 | 2008-08-27 | The Johns Hopkins University | Compositions and methods for the treatment or prevention of disorders relating to oxidative stress |
| DE102005041613A1 (de) | 2005-09-01 | 2007-03-08 | Ergonex Pharma Gmbh | Pharmazeutische Zusammensetzungen zur Behandlung von Karzinoid-Syndrom |
| JP5558719B2 (ja) | 2005-12-12 | 2014-07-23 | モサメディックス・ビー．ブイ． | 治療および診断におけるプレターゲッティングに適したアネキシン誘導体 |
| US8299046B2 (en) | 2006-11-17 | 2012-10-30 | Trustees Of Dartmouth College | Synthetic triterpenoids and tricyclic-bis-enones for use in stimulating bone and cartilage growth |
| EP2094651A1 (en) | 2006-11-17 | 2009-09-02 | Trustees Of Dartmouth College | Synthesis and biological activities of new tricyclic-bis-enones (tbes) |
| JP2008247898A (ja) | 2007-03-08 | 2008-10-16 | Santen Pharmaceut Co Ltd | トリテルペノイドを有効成分として含有する酸化ストレスが関連する眼疾患の予防又は治療剤 |
| WO2008136838A1 (en) | 2007-05-04 | 2008-11-13 | Trustees Of Dartmouth College | Novel amide derivatives of cddo and methods of use thereof |
| US20090048205A1 (en) | 2007-08-15 | 2009-02-19 | Colin Meyer | Combination therapy with synthetic triterpenoids and gemcitabine |
| US8088824B2 (en) * | 2007-08-15 | 2012-01-03 | Reata Pharmaceuticals Inc. | Forms of CDDO methyl ester |
| ME03529B (me) | 2008-01-11 | 2020-04-20 | Reata Pharmaceuticals Inc | Sintetički triterpenoidi i metode njihove upotrebe u tretmanu bolesti |
| WO2009146216A2 (en) | 2008-04-18 | 2009-12-03 | Reata Pharmaceuticals. Inc. | Antioxidant inflammation modulators: novel derivatives of oleanolic acid |
| EP2279197B1 (en) | 2008-04-18 | 2014-11-05 | Reata Pharmaceuticals, Inc. | Antioxidant inflammation modulators: oleanolic acid derivatives with saturation in the c-ring |
| SI2271658T1 (sl) | 2008-04-18 | 2017-03-31 | Reata Pharmaceuticals, Inc. | Antioksidantni modulatorji vnetja: C-17 homologirani derivati oleanolne kisline |
| CN102083442B (zh) | 2008-04-18 | 2014-08-13 | 里亚塔医药公司 | 抗氧化剂炎症调节剂：在c-17具有氨基和其它修饰的齐墩果酸衍生物 |
| CA2721665C (en) | 2008-04-18 | 2017-01-24 | Reata Pharmaceuticals, Inc. | Compounds including an anti-inflammatory pharmacore and methods of use |
| ES2449396T3 (es) | 2008-07-22 | 2014-03-19 | Trustees Of Dartmouth College | Cianoenonas monocíclicas y métodos de uso de las mismas |
| WO2010053817A1 (en) | 2008-11-04 | 2010-05-14 | Trustees Of Dartmouth College | Betulinic acid derivatives and methods of use thereof |
| HUE035013T2 (en) | 2009-02-13 | 2018-05-02 | Reata Pharmaceuticals Inc | Delayed release, oral dosage compositions that contain amorphous cddo-me |
| EP2558105B1 (en) | 2010-04-12 | 2019-11-20 | Reata Pharmaceuticals, Inc. | Bardoxolone methyl for the treatment of obesity |
| HUE044081T2 (hu) | 2011-03-11 | 2019-09-30 | Reata Pharmaceuticals Inc | C4 Monometil-triterpenoid-származékok, és módszerek azok alkalmazására |
-
1999
- 1999-06-17 US US09/335,003 patent/US6326507B1/en not_active Expired - Lifetime
- 1999-06-18 AT AT99928731T patent/ATE430563T1/de active
- 1999-06-18 DK DK99928731T patent/DK1089724T3/da active
- 1999-06-18 EP EP99928731A patent/EP1089724B1/en not_active Expired - Lifetime
- 1999-06-18 JP JP2000554358A patent/JP4541548B2/ja not_active Expired - Lifetime
- 1999-06-18 WO PCT/US1999/013635 patent/WO1999065478A1/en not_active Ceased
- 1999-06-18 EP EP09154222A patent/EP2062577A1/en not_active Withdrawn
- 1999-06-18 CA CA2335505A patent/CA2335505C/en not_active Expired - Lifetime
- 1999-06-18 PT PT99928731T patent/PT1089724E/pt unknown
- 1999-06-18 ES ES99928731T patent/ES2324966T3/es not_active Expired - Lifetime
-
2001
- 2001-08-09 US US09/927,081 patent/US6552075B2/en not_active Expired - Lifetime
-
2003
- 2003-03-24 US US10/395,372 patent/US7288568B2/en not_active Expired - Lifetime
-
2005
- 2005-05-03 US US11/121,316 patent/US7863327B2/en not_active Expired - Fee Related
-
2007
- 2007-10-29 US US11/927,418 patent/US8034955B2/en not_active Expired - Fee Related
-
2009
- 2009-06-05 JP JP2009136739A patent/JP5210971B2/ja not_active Expired - Lifetime
- 2009-07-15 CY CY20091100756T patent/CY1109256T1/el unknown
-
2011
- 2011-08-24 US US13/217,127 patent/US8586775B2/en not_active Expired - Fee Related
-
2012
- 2012-04-27 JP JP2012102499A patent/JP2012144574A/ja not_active Withdrawn
-
2013
- 2013-10-21 US US14/059,185 patent/US9278913B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20140275618A1 (en) | 2014-09-18 |
| US8034955B2 (en) | 2011-10-11 |
| PT1089724E (pt) | 2009-07-20 |
| ATE430563T1 (de) | 2009-05-15 |
| ES2324966T3 (es) | 2009-08-20 |
| US8586775B2 (en) | 2013-11-19 |
| US9278913B2 (en) | 2016-03-08 |
| EP1089724B1 (en) | 2009-05-06 |
| EP2062577A1 (en) | 2009-05-27 |
| US20130237721A1 (en) | 2013-09-12 |
| JP2002530272A (ja) | 2002-09-17 |
| US7288568B2 (en) | 2007-10-30 |
| CA2335505C (en) | 2010-06-15 |
| JP2009242409A (ja) | 2009-10-22 |
| WO1999065478A1 (en) | 1999-12-23 |
| CY1109256T1 (el) | 2014-07-02 |
| US6326507B1 (en) | 2001-12-04 |
| JP5210971B2 (ja) | 2013-06-12 |
| EP1089724A4 (en) | 2004-06-09 |
| US20080220057A1 (en) | 2008-09-11 |
| US20080234368A9 (en) | 2008-09-25 |
| JP2012144574A (ja) | 2012-08-02 |
| US20020042535A1 (en) | 2002-04-11 |
| US20050288363A1 (en) | 2005-12-29 |
| US6552075B2 (en) | 2003-04-22 |
| US20030236303A1 (en) | 2003-12-25 |
| US7863327B2 (en) | 2011-01-04 |
| CA2335505A1 (en) | 1999-12-23 |
| EP1089724A1 (en) | 2001-04-11 |
| DK1089724T3 (da) | 2009-07-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4541548B2 (ja) | 薬剤組成物及び使用方法 | |
| US6974801B2 (en) | Inhibitors and methods of use thereof | |
| JP4614884B2 (ja) | ピリドンの誘導体とその使用 | |
| JP4644829B2 (ja) | ヒストン脱アセチル化酵素阻害剤としての新規な化合物 | |
| US9925153B2 (en) | Therapeutic agents for skin diseases and conditions | |
| US20160367513A1 (en) | Compositions Including Androgen Receptor Degradation (ARD) Enhancers and Methods of Prophylactic or Therapeutic Treatment of Skin Disorders and Hair Loss | |
| CN1041204C (zh) | 用作拓扑酶抑制剂或细胞分化诱导物的五环三萜系化合物 | |
| US8710272B2 (en) | Compounds with (1 E, 6E)-1,7-bis-(3,4-dimethoxyphenyl)-4,4-disubstituted-hepta-1,6-diene-3,5-dione structural scaffold, their biological activity, and uses thereof | |
| WO2001068085A1 (en) | A method for stimulation of defensin production | |
| CN106619628B (zh) | 苦参碱衍生物在制备预防或治疗绝经后骨质疏松症药物中的应用 | |
| KR20050009737A (ko) | 다양한 질병, 질환 및 장애의 치료 또는 예방에 있어서아스코르브산과 결합한 안드로스탄 및 안드로스텐의신규한 유도체 및 그 용도 | |
| US9290455B2 (en) | CDDO-Me amino acid conjugates and methods of use | |
| HK40077325A (en) | Methods of inducing or enhancing farnesoid x receptor (fxr)-mediated transcriptional response | |
| WO2011046200A1 (ja) | 分化誘導因子又はその類縁体を含有する抗炎症剤 | |
| Balan et al. | Family of nuclear peroxisome proliferator—activated receptors (PPARs): biological role in metabolic adaptation. Part III. PPARγ and its role in autophagy, inflammation, carcinogenesis and reproductive system upon the exposure to xenobiotics (report 2) | |
| JPWO2000053563A1 (ja) | 核内リセプターｐｐａｒの新規リガンド | |
| KR20200092620A (ko) | 심바스타틴을 포함하는 관절염의 예방 또는 치료용 약학적 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20060606 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20060606 |
|
| RD02 | Notification of acceptance of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7422 Effective date: 20090130 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20090525 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20090605 |
|
| A524 | Written submission of copy of amendment under article 19 pct |
Free format text: JAPANESE INTERMEDIATE CODE: A524 Effective date: 20090605 |
|
| A871 | Explanation of circumstances concerning accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A871 Effective date: 20090605 |
|
| A975 | Report on accelerated examination |
Free format text: JAPANESE INTERMEDIATE CODE: A971005 Effective date: 20090618 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20090706 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20091002 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20091009 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20091105 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20091202 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20100318 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20100419 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20100531 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20100624 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4541548 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20130702 Year of fee payment: 3 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| EXPY | Cancellation because of completion of term |