CN102869353A - 自身免疫疾病的治疗 - Google Patents
自身免疫疾病的治疗 Download PDFInfo
- Publication number
- CN102869353A CN102869353A CN2011800224469A CN201180022446A CN102869353A CN 102869353 A CN102869353 A CN 102869353A CN 2011800224469 A CN2011800224469 A CN 2011800224469A CN 201180022446 A CN201180022446 A CN 201180022446A CN 102869353 A CN102869353 A CN 102869353A
- Authority
- CN
- China
- Prior art keywords
- alkyl
- alkoxy
- formula
- halogen
- compound
- 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.)
- Pending
Links
- 238000011282 treatment Methods 0.000 title claims abstract description 29
- 208000023275 Autoimmune disease Diseases 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 77
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 62
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 38
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 36
- 150000002367 halogens Chemical class 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 33
- 239000000651 prodrug Substances 0.000 claims abstract description 32
- 229940002612 prodrug Drugs 0.000 claims abstract description 32
- 239000012453 solvate Substances 0.000 claims abstract description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 125000004953 trihalomethyl group Chemical group 0.000 claims abstract description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 16
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 16
- 230000001363 autoimmune Effects 0.000 claims abstract description 15
- 208000017520 skin disease Diseases 0.000 claims abstract description 15
- -1 trifluoromethoxy, phenoxy, cyclohexylmethyloxy, pyridylmethoxy, cinnamyloxy, naphthylmethoxy, Phenoxymethyl Chemical group 0.000 claims abstract description 15
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 13
- 230000002265 prevention Effects 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims abstract description 9
- 125000004849 alkoxymethyl group Chemical group 0.000 claims abstract description 8
- 125000004768 (C1-C4) alkylsulfinyl group Chemical group 0.000 claims abstract description 7
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims abstract description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 6
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 6
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims abstract description 6
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 238000002360 preparation method Methods 0.000 claims abstract description 5
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000002252 acyl group Chemical group 0.000 claims abstract description 4
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 4
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 208000004921 cutaneous lupus erythematosus Diseases 0.000 claims description 42
- 208000011834 subacute cutaneous lupus erythematosus Diseases 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 18
- 206010025135 lupus erythematosus Diseases 0.000 claims description 14
- 230000000694 effects Effects 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 238000009094 second-line therapy Methods 0.000 claims description 8
- XXHKHLYABSAFDW-UHFFFAOYSA-N 5-amino-5-[2-chloro-4-(3-phenylmethoxyphenyl)sulfanylphenyl]pentane-1,3-diol Chemical compound C1=C(Cl)C(C(CC(O)CCO)N)=CC=C1SC1=CC=CC(OCC=2C=CC=CC=2)=C1 XXHKHLYABSAFDW-UHFFFAOYSA-N 0.000 claims description 7
- 230000002411 adverse Effects 0.000 claims description 6
- 238000009093 first-line therapy Methods 0.000 claims description 6
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- 208000006926 Discoid Lupus Erythematosus Diseases 0.000 claims description 4
- 208000011830 chronic cutaneous lupus erythematosus Diseases 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- 208000006802 Lupus erythematosus panniculitis Diseases 0.000 claims description 3
- JZHXIFZZZFFZBQ-XMMPIXPASA-N [(2r)-2-amino-4-[2-chloro-4-(3-phenylmethoxyphenyl)sulfanylphenyl]-2-(hydroxymethyl)butyl] dihydrogen phosphate Chemical compound C1=C(Cl)C(CC[C@](CO)(N)COP(O)(O)=O)=CC=C1SC1=CC=CC(OCC=2C=CC=CC=2)=C1 JZHXIFZZZFFZBQ-XMMPIXPASA-N 0.000 claims description 3
- JZHXIFZZZFFZBQ-DEOSSOPVSA-N [(2s)-2-amino-4-[2-chloro-4-(3-phenylmethoxyphenyl)sulfanylphenyl]-2-(hydroxymethyl)butyl] dihydrogen phosphate Chemical compound C1=C(Cl)C(CC[C@@](CO)(N)COP(O)(O)=O)=CC=C1SC1=CC=CC(OCC=2C=CC=CC=2)=C1 JZHXIFZZZFFZBQ-DEOSSOPVSA-N 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 230000001969 hypertrophic effect Effects 0.000 claims description 3
- 125000006372 monohalo methyl group Chemical group 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- 206010057887 neonatal lupus erythematosus Diseases 0.000 claims description 2
- 238000011321 prophylaxis Methods 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 8
- 229940079593 drug Drugs 0.000 abstract description 6
- 125000005843 halogen group Chemical group 0.000 abstract description 3
- 125000004970 halomethyl group Chemical group 0.000 abstract 1
- 229910019142 PO4 Inorganic materials 0.000 description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 7
- 239000010452 phosphate Substances 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 230000009885 systemic effect Effects 0.000 description 5
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 229960003433 thalidomide Drugs 0.000 description 4
- 230000000699 topical effect Effects 0.000 description 4
- 0 **1C=CC(COC(C=C(C=N)SC(C=*)=CC=C(*)C=C*)=CC=C*)=CC=C1 Chemical compound **1C=CC(COC(C=C(C=N)SC(C=*)=CC=C(*)C=C*)=CC=C*)=CC=C1 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 3
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000003430 antimalarial agent Substances 0.000 description 3
- 229940033495 antimalarials Drugs 0.000 description 3
- 229960002170 azathioprine Drugs 0.000 description 3
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 239000011737 fluorine Substances 0.000 description 3
- 229960000485 methotrexate Drugs 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- RMIKUOHVGYDMNH-UHFFFAOYSA-N 2-amino-4-[2-chloro-4-(3-phenylmethoxyphenyl)sulfanylphenyl]-2-ethylbutan-1-ol Chemical compound C1=C(Cl)C(CCC(N)(CO)CC)=CC=C1SC1=CC=CC(OCC=2C=CC=CC=2)=C1 RMIKUOHVGYDMNH-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 208000001388 Opportunistic Infections Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000000747 cardiac effect Effects 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 239000003974 emollient agent Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229960003444 immunosuppressant agent Drugs 0.000 description 2
- 239000003018 immunosuppressive agent Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000011519 second-line treatment Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000009095 third-line therapy Methods 0.000 description 2
- APNSMSZFHDYDHX-UHFFFAOYSA-N 2-amino-4-[2-chloro-4-(3-phenylmethoxyphenyl)sulfanylphenyl]-2-methylbutan-1-ol Chemical compound C1=C(Cl)C(CCC(N)(CO)C)=CC=C1SC1=CC=CC(OCC=2C=CC=CC=2)=C1 APNSMSZFHDYDHX-UHFFFAOYSA-N 0.000 description 1
- BWWHTIHDQBHTHP-UHFFFAOYSA-N 2-nitrobenzoyl chloride Chemical compound [O-][N+](=O)C1=CC=CC=C1C(Cl)=O BWWHTIHDQBHTHP-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 208000006820 Arthralgia Diseases 0.000 description 1
- 206010003671 Atrioventricular Block Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 206010051055 Deep vein thrombosis Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010061819 Disease recurrence Diseases 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 150000008575 L-amino acids Chemical class 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010034972 Photosensitivity reaction Diseases 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 208000012658 Skin autoimmune disease Diseases 0.000 description 1
- 206010043275 Teratogenicity Diseases 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 1
- 206010047249 Venous thrombosis Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000001574 biopsy Methods 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 1
- 238000004737 colorimetric analysis Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 230000010339 dilation Effects 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000009266 disease activity Effects 0.000 description 1
- 230000006806 disease prevention Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000035622 drinking Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 208000024963 hair loss Diseases 0.000 description 1
- 230000003676 hair loss Effects 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 238000002650 immunosuppressive therapy Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- KUKSUQKELVOKBH-UHFFFAOYSA-N n-[bis[(2-methylpropan-2-yl)oxy]phosphanyl]-n-ethylethanamine Chemical compound CCN(CC)P(OC(C)(C)C)OC(C)(C)C KUKSUQKELVOKBH-UHFFFAOYSA-N 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000008816 organ damage Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000004344 phenylpropyl group Chemical group 0.000 description 1
- 230000036211 photosensitivity Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000037390 scarring Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007390 skin biopsy Methods 0.000 description 1
- 206010040882 skin lesion Diseases 0.000 description 1
- 231100000444 skin lesion Toxicity 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 231100000211 teratogenicity Toxicity 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 210000001835 viscera Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/66—Phosphorus compounds
- A61K31/661—Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion or mevinphos
-
- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C321/00—Thiols, sulfides, hydropolysulfides or polysulfides
- C07C321/24—Thiols, sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings
- C07C321/28—Sulfides, hydropolysulfides, or polysulfides having thio groups bound to carbon atoms of six-membered aromatic rings
- C07C321/30—Sulfides having the sulfur atom of at least one thio group bound to two carbon atoms of six-membered aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP10162079 | 2010-05-06 | ||
| EP10162079.7 | 2010-05-06 | ||
| PCT/EP2011/057203 WO2011138393A1 (en) | 2010-05-06 | 2011-05-05 | Treatment of autoimmune diseases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102869353A true CN102869353A (zh) | 2013-01-09 |
Family
ID=42199281
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2011800224469A Pending CN102869353A (zh) | 2010-05-06 | 2011-05-05 | 自身免疫疾病的治疗 |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US20130172297A1 (enExample) |
| EP (1) | EP2566470A1 (enExample) |
| JP (1) | JP2013530937A (enExample) |
| KR (1) | KR20130066630A (enExample) |
| CN (1) | CN102869353A (enExample) |
| AU (1) | AU2011249784B2 (enExample) |
| BR (1) | BR112012028190A2 (enExample) |
| CA (1) | CA2795394A1 (enExample) |
| CL (1) | CL2012003091A1 (enExample) |
| CR (1) | CR20120566A (enExample) |
| CU (1) | CU20120154A7 (enExample) |
| EA (1) | EA201201514A1 (enExample) |
| EC (1) | ECSP12012312A (enExample) |
| IL (1) | IL222690A0 (enExample) |
| MA (1) | MA34285B1 (enExample) |
| MX (1) | MX2012012926A (enExample) |
| NZ (1) | NZ603999A (enExample) |
| PE (1) | PE20130612A1 (enExample) |
| PH (1) | PH12012502418A1 (enExample) |
| SG (1) | SG185746A1 (enExample) |
| TN (1) | TN2012000509A1 (enExample) |
| TW (1) | TW201201814A (enExample) |
| WO (1) | WO2011138393A1 (enExample) |
| ZA (1) | ZA201207710B (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI519539B (zh) | 2010-12-21 | 2016-02-01 | Kyorin Seiyaku Kk | Diphenyl sulfide derivatives and pharmaceuticals as an active ingredient thereof |
| US9289494B2 (en) | 2013-11-20 | 2016-03-22 | RestorTears, LLC | Method of treating ocular disorders with compounds found in Harderian gland secretions |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003029184A1 (en) | 2001-09-27 | 2003-04-10 | Kyorin Pharmaceutical Co., Ltd. | Diaryl ether derivative, addition salt thereof, and immunosuppressant |
| AU2002332289B2 (en) * | 2001-09-27 | 2007-05-10 | Kyorin Pharmaceutical Co., Ltd. | Diaryl sulfide derivative, addition salt thereof, and immunosuppressant |
| US7482491B2 (en) | 2002-09-19 | 2009-01-27 | Kyorin Pharmaceutical Co., Ltd. | Amino alcohol derivative, addition salt thereof, and immunosuppressant |
| WO2004074297A1 (ja) * | 2003-02-18 | 2004-09-02 | Kyorin Pharmaceutical Co., Ltd. | アミノホスホン酸誘導体とその付加塩及びs1p受容体調節剤 |
| ES2351393T3 (es) * | 2003-05-26 | 2011-02-03 | Takeda Pharmaceutical Company Limited | Sulfopirroles. |
| MXPA06002349A (es) | 2003-08-28 | 2006-05-22 | Novartis Ag | Derivados de aminopropanol. |
| CN1918148B (zh) * | 2004-02-11 | 2012-09-05 | 巴斯利尔药物股份公司 | 取代的苯并咪唑和它们诱导细胞凋亡的用途 |
| JPWO2006041015A1 (ja) * | 2004-10-12 | 2008-05-15 | 杏林製薬株式会社 | アミノアルコール誘導体とその付加塩及び免疫抑制剤 |
| GB0504544D0 (en) * | 2005-03-04 | 2005-04-13 | Novartis Ag | Organic compounds |
| CA2820510A1 (en) * | 2005-09-09 | 2007-03-15 | Novartis Ag | Treatment of autoimmune diseases |
-
2011
- 2011-05-05 KR KR1020127031868A patent/KR20130066630A/ko not_active Withdrawn
- 2011-05-05 US US13/643,320 patent/US20130172297A1/en not_active Abandoned
- 2011-05-05 MX MX2012012926A patent/MX2012012926A/es not_active Application Discontinuation
- 2011-05-05 TW TW100115816A patent/TW201201814A/zh unknown
- 2011-05-05 PH PH1/2012/502418A patent/PH12012502418A1/en unknown
- 2011-05-05 EP EP11723889A patent/EP2566470A1/en not_active Withdrawn
- 2011-05-05 CA CA2795394A patent/CA2795394A1/en not_active Abandoned
- 2011-05-05 WO PCT/EP2011/057203 patent/WO2011138393A1/en not_active Ceased
- 2011-05-05 AU AU2011249784A patent/AU2011249784B2/en not_active Ceased
- 2011-05-05 CN CN2011800224469A patent/CN102869353A/zh active Pending
- 2011-05-05 BR BR112012028190A patent/BR112012028190A2/pt not_active IP Right Cessation
- 2011-05-05 PE PE2012002122A patent/PE20130612A1/es not_active Application Discontinuation
- 2011-05-05 EA EA201201514A patent/EA201201514A1/ru unknown
- 2011-05-05 SG SG2012086526A patent/SG185746A1/en unknown
- 2011-05-05 JP JP2013508502A patent/JP2013530937A/ja active Pending
- 2011-05-05 NZ NZ603999A patent/NZ603999A/en not_active IP Right Cessation
- 2011-05-05 MA MA35416A patent/MA34285B1/fr unknown
-
2012
- 2012-10-15 ZA ZA2012/07710A patent/ZA201207710B/en unknown
- 2012-10-23 TN TNP2012000509A patent/TN2012000509A1/en unknown
- 2012-10-25 IL IL222690A patent/IL222690A0/en unknown
- 2012-11-05 CU CU2012000154A patent/CU20120154A7/es unknown
- 2012-11-06 CR CR20120566A patent/CR20120566A/es unknown
- 2012-11-06 CL CL2012003091A patent/CL2012003091A1/es unknown
- 2012-11-27 EC ECSP12012312 patent/ECSP12012312A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EA201201514A1 (ru) | 2013-05-30 |
| ECSP12012312A (es) | 2012-12-28 |
| AU2011249784A1 (en) | 2012-12-20 |
| TN2012000509A1 (en) | 2014-04-01 |
| CA2795394A1 (en) | 2011-11-10 |
| KR20130066630A (ko) | 2013-06-20 |
| TW201201814A (en) | 2012-01-16 |
| AU2011249784B2 (en) | 2014-03-06 |
| WO2011138393A1 (en) | 2011-11-10 |
| PH12012502418A1 (en) | 2018-03-21 |
| SG185746A1 (en) | 2013-01-30 |
| ZA201207710B (en) | 2013-06-26 |
| NZ603999A (en) | 2014-06-27 |
| PE20130612A1 (es) | 2013-06-06 |
| CU20120154A7 (es) | 2013-03-27 |
| MA34285B1 (fr) | 2013-06-01 |
| IL222690A0 (en) | 2012-12-31 |
| US20130172297A1 (en) | 2013-07-04 |
| CR20120566A (es) | 2013-01-09 |
| CL2012003091A1 (es) | 2013-03-22 |
| BR112012028190A2 (pt) | 2016-08-02 |
| MX2012012926A (es) | 2012-12-17 |
| JP2013530937A (ja) | 2013-08-01 |
| EP2566470A1 (en) | 2013-03-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR101698028B1 (ko) | 수용성 아세트아미노펜 유사체 | |
| CN110305095A (zh) | 色甘酸衍生物以及成像和治疗的相关方法 | |
| CN103619330A (zh) | 用于治疗糖尿病的选择性雄激素受体调节剂 | |
| CN107001806B (zh) | 用于治疗心肺疾病的鞘氨醇-1-磷酸盐受体调节剂 | |
| JP2017019854A (ja) | 自己免疫性疾患の処置剤 | |
| CN105985295B (zh) | 一种旋光纯的硫代乙酸类化合物 | |
| WO2022140397A1 (en) | Methods of treating cancer | |
| CN102869353A (zh) | 自身免疫疾病的治疗 | |
| CN112118843B (zh) | 使用吲哚化合物治疗疼痛或间质性膀胱炎的方法 | |
| EP4349341A1 (en) | Pharmaceutical preparation for preventing or treating pulmonary fibrosis | |
| JP6290963B2 (ja) | ジアリールスルフィド誘導体の投与レジメン | |
| WO2018013625A1 (en) | Deuterated miconazole | |
| US20080207667A1 (en) | Use of nalbuphine and related compounds to treat symptoms of respiratory problems | |
| JP4829478B2 (ja) | 医薬組成物 | |
| BR112021013637A2 (pt) | Inibidores da síntese de leucotrieno | |
| US20250002512A1 (en) | Novel anti-depressant and neuroplastic agents and therapeutic uses thereof | |
| JP5765650B2 (ja) | インフルエンザウイルス感染症の予防および/または治療剤 | |
| TW201806601A (zh) | σ受體配體在皰疹後遺疼痛中的用途 | |
| CN114874202A (zh) | 一种用于治疗阿尔茨海默症的药物及其用途 | |
| JP2024536229A (ja) | Irhom2阻害剤及びその使用 | |
| JP2004331661A (ja) | 医薬組成物 | |
| HK40049577A (en) | Indole compound for treating interstitial cystitis | |
| HK40049577B (en) | Indole compound for treating interstitial cystitis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C53 | Correction of patent of invention or patent application | ||
| CB02 | Change of applicant information |
Address after: Basel Applicant after: Novartis Ag Address before: Basel Applicant before: Novartis AG |
|
| COR | Change of bibliographic data |
Free format text: CORRECT: APPLICANT; FROM: NOVARTIS AG TO: NOVARTIS CO., LTD. |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20130109 |