HRP20201089T1 - Postupak sinteze inhibitora indolamin 2,3-dioksigenaze - Google Patents
Postupak sinteze inhibitora indolamin 2,3-dioksigenaze Download PDFInfo
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- HRP20201089T1 HRP20201089T1 HRP20201089TT HRP20201089T HRP20201089T1 HR P20201089 T1 HRP20201089 T1 HR P20201089T1 HR P20201089T T HRP20201089T T HR P20201089TT HR P20201089 T HRP20201089 T HR P20201089T HR P20201089 T1 HRP20201089 T1 HR P20201089T1
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- 238000000034 method Methods 0.000 title claims 27
- 229940113303 Indoleamine 2,3-dioxygenase inhibitor Drugs 0.000 title 1
- 230000015572 biosynthetic process Effects 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 47
- 239000003638 chemical reducing agent Substances 0.000 claims 14
- 238000006243 chemical reaction Methods 0.000 claims 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 8
- -1 9-fluorenylmethyloxycarbonyl Chemical group 0.000 claims 7
- 238000010511 deprotection reaction Methods 0.000 claims 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims 6
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical group CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 5
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 4
- 150000007524 organic acids Chemical class 0.000 claims 4
- 125000006239 protecting group Chemical group 0.000 claims 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 2
- 230000008878 coupling Effects 0.000 claims 2
- 238000010168 coupling process Methods 0.000 claims 2
- 238000005859 coupling reaction Methods 0.000 claims 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims 2
- 239000000203 mixture Substances 0.000 claims 2
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims 2
- 239000003223 protective agent Substances 0.000 claims 2
- 239000012321 sodium triacetoxyborohydride Substances 0.000 claims 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical group NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 1
- MOHYOXXOKFQHDC-UHFFFAOYSA-N 1-(chloromethyl)-4-methoxybenzene Chemical compound COC1=CC=C(CCl)C=C1 MOHYOXXOKFQHDC-UHFFFAOYSA-N 0.000 claims 1
- IJIVZRMITPUVAC-UHFFFAOYSA-N 2,2,2-trichloroethyl N-(2,2-dimethoxyethylsulfamoyl)carbamate Chemical compound COC(CNS(=O)(=O)NC(=O)OCC(Cl)(Cl)Cl)OC IJIVZRMITPUVAC-UHFFFAOYSA-N 0.000 claims 1
- 125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims 1
- HUYOMBHZNMTQPT-UHFFFAOYSA-N 9H-fluoren-9-ylmethyl N-(2,2-dimethoxyethylsulfamoyl)carbamate Chemical compound COC(CNS(=O)(=O)NC(=O)OCC1c2ccccc2-c2ccccc12)OC HUYOMBHZNMTQPT-UHFFFAOYSA-N 0.000 claims 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims 1
- 150000001299 aldehydes Chemical class 0.000 claims 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 claims 1
- FEJQZESDPWHUIU-UHFFFAOYSA-N benzyl N-(2,2-dimethoxyethylsulfamoyl)carbamate Chemical compound COC(CNS(=O)(=O)NC(=O)OCc1ccccc1)OC FEJQZESDPWHUIU-UHFFFAOYSA-N 0.000 claims 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 claims 1
- 239000000460 chlorine Substances 0.000 claims 1
- 229910052801 chlorine Inorganic materials 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- KGVDNTXHSSRDTB-UHFFFAOYSA-N ethyl N-(2,2-dimethoxyethylsulfamoyl)carbamate Chemical compound CCOC(=O)NS(=O)(=O)NCC(OC)OC KGVDNTXHSSRDTB-UHFFFAOYSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- JETYSCOMGBXHSL-UHFFFAOYSA-N tert-butyl N-(2,2-dimethoxyethylsulfamoyl)carbamate Chemical compound COC(CNS(=O)(=O)NC(=O)OC(C)(C)C)OC JETYSCOMGBXHSL-UHFFFAOYSA-N 0.000 claims 1
- QFUUIYBSWTYLNT-UHFFFAOYSA-N tert-butyl N-[(4-methoxyphenyl)methyl]-N-[(4-methoxyphenyl)methyl-(2-oxoethyl)sulfamoyl]carbamate Chemical compound COc1ccc(CN(CC=O)S(=O)(=O)N(Cc2ccc(OC)cc2)C(=O)OC(C)(C)C)cc1 QFUUIYBSWTYLNT-UHFFFAOYSA-N 0.000 claims 1
- VNDJTNFKQAFSLL-UHFFFAOYSA-N tert-butyl N-[2-oxoethyl(prop-2-enyl)sulfamoyl]-N-prop-2-enylcarbamate Chemical compound CC(C)(C)OC(=O)N(CC=C)S(=O)(=O)N(CC=C)CC=O VNDJTNFKQAFSLL-UHFFFAOYSA-N 0.000 claims 1
- 239000011701 zinc Substances 0.000 claims 1
- 229910052725 zinc Inorganic materials 0.000 claims 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4245—Oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C307/00—Amides of sulfuric acids, i.e. compounds having singly-bound oxygen atoms of sulfate groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C307/04—Diamides of sulfuric acids
- C07C307/06—Diamides of sulfuric acids having nitrogen atoms of the sulfamide groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/04—1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/08—1,2,5-Oxadiazoles; Hydrogenated 1,2,5-oxadiazoles
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Indole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Claims (29)
1. Postupak koji obuhvaća reagiranje spoja formule F5:
[image]
s aldehidom formule F6:
[image]
pri čemu je Pg1amino zaštitna grupa, da se dobije spoj formule F7:
[image]
2. Postupak prema zahtjevu 1, pri čemu je Pg1 :
(a) etoksikarbonil, terc-butoksikarbonil, benziloksikarbonil, ili 9-fluorenilmetiloksikarbonil; ili
(b) terc-butoksikarbonil.
3. Postupak prema bilo kojem zahtjevu 1-2, pri čemu se spomenuta reakcija izvodi u prisustvu redukcijskog sredstva, gdje je spomenuto redukcijsko sredstvo:
(a) borhidridno redukcijsko sredstvo; ili
(b) borhidridno redukcijsko sredstvo koje je natrijev triacetoksiborohidrid.
4. Postupak prema bilo kojem zahtjevu 1-3, koji dalje obuhvaća uklanjanje zaštite spomenutog spoja formule F7 da se dobije spoj formule F8:
[image]
opcionalno gdje spomenuto uklanjanje zaštitne grupe uključuje reagiranje spoja formule F7 sa klorovodičnom kiselinom.
5. Postupak prema zahtjevu 4, koji dalje obuhvaća reagiranje spomenutog spoja formule F8, sa Pg2-NH-SO2-X, u prisustvu organske baze da se dobije spoj formule F9:
[image]
pri čemu:
Pg2 je amino zaštitna grupa; i
X je halo.
6. Postupak prema zahtjevu 5, pri čemu je Pg2 :
(a) etoksikarbonil, terc-butoksikarbonil, benziloksikarbonil, ili 9-fluorenilmetiloksikarbonil; ili
(b) terc-butoksikarbonil; i pri čemu X je klor.
7. Postupak prema bilo kojem zahtjevu 5-6, koji dalje obuhvaća i uklanjanje zaštite spomenutog spoja formule F9 da se dobije spoj formule F10:
[image]
opcionalno gdje spomenuto uklanjanje zaštitne grupe obuhvaća reagiranje spoja formule F9 sa klorovodičnom kiselinom.
8. Postupak prema zahtjevu 7, koji dalje obuhvaća reagiranje spomenutog spoja formule F10 sa bazom da se dobije spoj formule I:
[image]
opcionalno gdje je spomenuta baza natrijev hidroksid.
9. Postupak, koji obuhvaća reagiranje spoja formule F15:
[image]
sa spojem formule F5:
[image]
da se dobije spoj formule F16:
[image]
pri čemu:
svaki R1 je nezavisno amino zaštitna grupa izabrana od C2-4 alkenil-C1-3 alkil ili fenil-C1-3 alkil, pri čemu je spomenuti fenil-C1-3 alkil opcionalno supstituiran sa 1, 2, ili 3 nezavisno izabranih C1-4 alkoksi grupa;
i
R3 je C1-6 alkil ili benzil.
10. Postupak prema zahtjevu 9, pri čemu:
(a) svaki R1 je alil;
(b) svaki R1 je 4-metoksibenzil;
(c) R3 je C1-6 alkil; ili
(d) R3 je terc-butil.
11. Postupak prema bilo kojem zahtjevu 9-10, pri se čemu spomenuta reakcija izvodi u prisustvu redukcijskog sredstva, gdje je spomenuto redukcijsko sredstvo:
(a) borohidridno redukcijsko sredstvo; ili
(b) borohidridno redukcijsko sredstvo koje je natrijev triacetoksiborhidrid; i gdje se spomenuta reakcija izvodi u prisustvu trifluoroctene kiseline.
12. Postupak prema bilo kojem zahtjevu 9-11, koji dalje obuhvaća uklanjanje zaštite spomenutog spoja formule F16 da se dobije spoj formule F10:
[image]
pri čemu spomenuto uklanjanje zaštite obuhvaća:
(a) reagiranje spoja formule F16 sa trifluoroctenom kiselinom; ili
(b) reagiranje spojaformule F16 sa klorovodičnom kiselinom.
13. Postupak prema bilo kojem zahtjevu 9-12, pri čemu je spomenuti spoj formule F15 dobijen postupkom koji obuhvaća tretiranje spoja formule F14:
[image]
sa redukcijskim sredstvom da se dobije spomenuti spoj formule F15; pri čemu R2 je C1-4 alkil; opcionalno gdje je spomenuto redukcijsko sredstvo diizobutilaluminijev hidrid.
14. Postupak prema zahtjevu 13, pri čemu je spomenuti spoj formule F14 dobijen postupkom koji obuhvaća zaštitu spoja formule F13:
[image]
s jednim ili više nezavisno izabranih amino zaštitnih sredstava da se dobije spoj formule F14; opcionalno gdje je spomenuto jedno ili više amino zaštitnih sredstava izabrano od alil bromida i 4-metoksibenzil klorida, i gdje se spomenuta zaštita izvodi u prisustvu baze.
15. Spoj formule F15:
[image]
pri čemu:
R3 je C1-6 alkil ili benzil; i
svaki R1 je nezavisno amino zaštitna grupa.
16. Spoj prema zahtjevu 15, koji je:
(a) terc-butil alil{[alil(2-oksoetil)amino] sulfonil} karbamat; ili
(b) terc-butil(4-metoksibenzil){[(4-metoksibenzil)(2-oksoetil)amino] sulfonil} karbamat.
17. Postupak, koji obuhvaća reagiranje spoja formule F17:
[image]
pri čemu R4 je C1-6 alkil, C1-6 haloalkil, benzil, ili 9H-fluoren-9-ilmetil sa spojem formule F5:
[image]
da se dobije spoj formule F18:
[image]
18. Postupak prema zahtjevu 17, pri čemu R4 je:
(a) terc-butil;
(b) benzil;
(c) etil; ili
(d) 2,2,2-trikloretil.
19. Postupak prema zahtjevu 18, pri čemu se spomenuta reakcija izvodi u prisustvu redukcijskog sredstva; opcionalno gdje je spomenuto redukcijskog sredstvo trietilsilan, i gdje se spomenuta reakcija izvodi u prisustvu organske kiseline; opcionalno gdje je spomenuta organska kiselina trifluoroctena kiselina.
20. Postupak prema bilo kojem zahtjevu 18-19, koji dalje obuhvaća uklanjanje zaštite spomenutog spoja formule F18 da se dobije spoj formule F10:
[image]
opcionalno gdje spomenuto uklanjanje zaštitne grupe uključuje reagiranje spoja formule F18 sa cinkom u prisustvu octenekiseline.
21. Postupak prema zahtjevu 20, koji dalje obuhvaća reagiranje spomenutog spoja formule F10 sa bazom da se dobije spoj formule I:
[image]
opcionalno gdje je spomenuta baza natrijev hidroksid.
22. Postupak prema zahtjevu 17, pri čemu R4 je 9H-fluoren-9-ilmetil.
23. Postupak prema zahtjevu 22, pri čemu se spomenuta reakcija izvodi u prisustvu redukcijskog sredstva; opcionalno gdje je spomenuto redukcijsko sredstvo trietilsilan; i gdje se spomenuta reakcija izvodi u prisustvu organske kiseline; opcionalno gdje je spomenuta organska kiselina metansulfonska kiselina.
24. Postupak prema bilo kojem zahtjevu 22-23, koji dalje obuhvaća pretvaranje spomenutog spoja formule F18 u spoj formule I:
[image]
pri čemu spomenuto pretvaranje obuhvaća spajanje spoja formule F18 sa bazom da bi se formirala prva smjesa; opcionalno gdje je spomenuta baza N,N-bis(2-aminoetil)etan-1,2-diamin.
25. Postupak prema zahtjevu 24, pri čemu spomenuto pretvaranje dalje obuhvaća dodavanje vodene klorovodične kiseline u spomenutu prvu smjesu.
26. Spoj formule F17:
[image]
gdje je R4C1-6 haloalkil, benzil, ili 9H-fluoren-9-ilmetil.
27. Spoj prema zahtjevu 26, koji je:
(a) benzil N-(2,2-dimetoksietil)sulfamoilkarbamat;
(b) 2,2,2-trikloretil N-(2,2-dimetoksietil)sulfamoilkarbamat; ili
(c) (9H-fluoren-9-il)metil N-(2,2-dimetoksietil)sulfamoilkarbamat.
28. Spoj koji je:
(a) terc-butil N-(2,2-dimetoksietil)sulfamoilkarbamat; ili
(b) etil N-(2,2-dimetoksietil)sulfamoilkarbamat.
29. Postupak, koji obuhvaća:
i) reagiranje spoja formule F19:
[image]
sa spojem formule F5:
[image]
u prisustvu trietilsilana i metansulfonske kiseline da se dobije spoj formule F20:
[image]
i
ii) pretvaranje spomenutog spoja formule F20 u spoj formule I:
[image]
gdje spomenuto pretvaranje obuhvaća spajanje spomenutog spoja formule F20 sN,N-bis(2-aminoetil)etan-1,2-diaminom.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US201361901689P | 2013-11-08 | 2013-11-08 | |
EP14812015.7A EP3066085B1 (en) | 2013-11-08 | 2014-11-07 | Process for the synthesis of an indoleamine 2,3-dioxygenase inhibitor |
PCT/US2014/064531 WO2015070007A1 (en) | 2013-11-08 | 2014-11-07 | Process for the synthesis of an indoleamine 2,3-dioxygenase inhibitor |
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Publication Number | Publication Date |
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HRP20201089T1 true HRP20201089T1 (hr) | 2020-10-30 |
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HRP20201089TT HRP20201089T1 (hr) | 2013-11-08 | 2020-07-13 | Postupak sinteze inhibitora indolamin 2,3-dioksigenaze |
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US (3) | US9321755B2 (hr) |
EP (2) | EP3744715A1 (hr) |
JP (4) | JP6461953B2 (hr) |
KR (2) | KR102370067B1 (hr) |
CN (2) | CN109810104B (hr) |
AR (1) | AR098343A1 (hr) |
AU (2) | AU2014346647B2 (hr) |
BR (2) | BR122020009912B1 (hr) |
CA (1) | CA2929552C (hr) |
CL (1) | CL2016001082A1 (hr) |
CR (2) | CR20160252A (hr) |
CY (1) | CY1123164T1 (hr) |
DK (1) | DK3066085T3 (hr) |
EA (2) | EA033667B1 (hr) |
ES (1) | ES2799582T3 (hr) |
HR (1) | HRP20201089T1 (hr) |
HU (1) | HUE049337T2 (hr) |
IL (2) | IL245314B (hr) |
LT (1) | LT3066085T (hr) |
ME (1) | ME03792B (hr) |
MX (2) | MX366874B (hr) |
MY (1) | MY174254A (hr) |
PE (2) | PE20220430A1 (hr) |
PH (2) | PH12016500818B1 (hr) |
PL (1) | PL3066085T3 (hr) |
PT (1) | PT3066085T (hr) |
RS (1) | RS60598B1 (hr) |
SG (2) | SG10201803874PA (hr) |
SI (1) | SI3066085T1 (hr) |
TW (4) | TWI696618B (hr) |
WO (1) | WO2015070007A1 (hr) |
Families Citing this family (26)
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---|---|---|---|---|
KR101562549B1 (ko) | 2005-05-10 | 2015-10-23 | 인사이트 홀딩스 코포레이션 | 인돌아민 2,3-디옥시게나제의 조절제 및 이의 사용방법 |
EA029781B1 (ru) | 2008-07-08 | 2018-05-31 | Инсайт Корпорейшн | 1,2,5-оксадиазолы в качестве ингибиторов индоламин-2,3-диоксигеназы |
GB201311888D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compounds |
GB201311891D0 (en) | 2013-07-03 | 2013-08-14 | Glaxosmithkline Ip Dev Ltd | Novel compound |
SI3066085T1 (sl) | 2013-11-08 | 2020-08-31 | Incyte Holdings Corporation | Postopek sinteze inhibitorja indolamina 2,3-dioksigenaze |
KR20160108568A (ko) * | 2014-02-04 | 2016-09-19 | 인사이트 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 ido1 억제제의 조합 |
US20180271861A1 (en) * | 2015-07-14 | 2018-09-27 | Kyowa Hakko Kirin Co., Ltd. | Therapeutic agent for a tumor comprising an ido inhibitor administered in combination with an antibody |
JP2018532756A (ja) | 2015-11-04 | 2018-11-08 | インサイト・コーポレイションIncyte Corporation | インドールアミン2,3−ジオキシゲナーゼを阻害するための医薬組成物と方法、及びその適応 |
US10538497B2 (en) | 2015-12-15 | 2020-01-21 | Merck Sharp & Dohme Corp. | Compounds as indoleamine 2,3-dioxygenase inhibitors |
US9624185B1 (en) * | 2016-01-20 | 2017-04-18 | Yong Xu | Method for preparing IDO inhibitor epacadostat |
CN105646389B (zh) * | 2016-01-28 | 2019-06-28 | 中国科学院上海有机化学研究所 | 一种作为吲哚胺-2,3-双加氧酶抑制剂的氨基磺酸脂及其制备方法和用途 |
CN107304191B (zh) * | 2016-04-20 | 2023-09-29 | 上海翰森生物医药科技有限公司 | 吲哚胺2,3-双加氧酶抑制剂及其制备方法与应用 |
WO2017181849A1 (zh) * | 2016-04-20 | 2017-10-26 | 江苏豪森药业集团有限公司 | 吲哚胺2,3-双加氧酶抑制剂及其制备方法与应用 |
EP3505517A4 (en) | 2016-08-23 | 2020-01-15 | Beijing InnoCare Pharma Tech Co., Ltd. | FUSED HETEROCYCLIC DERIVATIVE, ITS PREPARATION METHOD AND ITS MEDICAL USE |
EP3515914A4 (en) | 2016-09-24 | 2020-04-15 | BeiGene, Ltd. | NEW IMIDAZO [1,5-A] PYRIDINES SUBSTITUTED IN POSITION 5 OR 8 AS INDOLEAMINE AND / OR TRYPTOPHANE 2,3-DIOXYGENASES |
EP3544965A4 (en) * | 2016-11-28 | 2020-05-20 | Shanghai Fochon Pharmaceutical Co., Ltd. | SULFOXIMIN, SULFONIMIDAMID, SULFONDIIMIN AND DIIMIDOSULFONAMID COMPOUNDS AS INHIBITORS OF INDOLAMINE-2,3-DIOXYGENASE |
ES2970715T3 (es) | 2016-12-22 | 2024-05-30 | Prec Pharmaceuticals Inc | Composiciones y métodos para inhibir la actividad de la arginasa |
CN109206380A (zh) * | 2017-07-03 | 2019-01-15 | 上海时莱生物技术有限公司 | 吲哚胺2,3-双加氧酶抑制剂化合物及其制备方法和用途 |
CN110066253B (zh) * | 2018-01-24 | 2023-06-23 | 江苏柯菲平医药股份有限公司 | 1,2,5-噁二唑类衍生物,其制备方法及其在医药中的应用 |
CN108101899B (zh) * | 2018-02-11 | 2021-01-26 | 中国药科大学 | IDO1抑制剂Epacadostat中间体的制备方法 |
CN109180603A (zh) * | 2018-10-10 | 2019-01-11 | 中国药科大学 | Epacadostat关键中间体的制备方法 |
EP4007602A1 (en) | 2019-08-01 | 2022-06-08 | Incyte Corporation | A dosing regimen for an ido inhibitor |
JP2023501496A (ja) * | 2019-11-14 | 2023-01-18 | ノバ サウスイースタン ユニバーシティー | F16イソインドール小分子を使用する固形腫瘍の治療のための方法及び組成物 |
CN112341403B (zh) * | 2020-11-10 | 2022-06-28 | 南京工业大学 | 一种利用微流场反应技术制备3-氨基-4-偕胺肟基呋咱的方法 |
EP4301358A2 (en) | 2021-03-05 | 2024-01-10 | Universität Basel Vizerektorat Forschung | Compositions for the treatment of ebv associated diseases or conditions |
EP4052705A1 (en) | 2021-03-05 | 2022-09-07 | Universität Basel Vizerektorat Forschung | Compositions for the treatment of ebv associated diseases or conditions |
Family Cites Families (73)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3236855A (en) | 1964-01-17 | 1966-02-22 | Merck & Co Inc | Certain n-phenyl(thiazole-hydroxamidine) compounds and their preparation |
US3354174A (en) | 1964-02-19 | 1967-11-21 | Sterling Drug Inc | 1-and 2-benzimidazolyl-lower-alkylamidoximes, amidines-, and guanidines |
US3553228A (en) | 1967-09-26 | 1971-01-05 | Colgate Palmolive Co | 3-substituted-4h(1)benzopyrano(3,4-d) isoxazoles |
DE2040628A1 (de) | 1970-08-17 | 1972-02-24 | Fahlberg List Veb | Neue herbizide Mittel |
US3948928A (en) | 1972-03-17 | 1976-04-06 | Dainippon Pharmaceutical Co., Ltd. | 3-Substituted-1,2-benzisoxazoles and pharmaceutically acceptable acid addition salts thereof |
JPS5621033B2 (hr) | 1973-09-05 | 1981-05-16 | ||
DE2640484A1 (de) | 1975-09-11 | 1977-04-07 | Philagro Sa | Amidoxim-derivate, ihre herstellung und verwendung |
FR2323683A1 (fr) | 1975-09-11 | 1977-04-08 | Philagro Sa | Nouveaux derives d'amidoximes, leur preparation et les compositions qui les contiennent |
US4323681A (en) | 1980-09-29 | 1982-04-06 | American Home Products Corporation | 4-Amino-2-substituted-5-pyrimidinecarboxamidoximes and carbothioamides |
JPS58208275A (ja) | 1982-05-20 | 1983-12-03 | Lion Corp | 5−アミノ−ピラゾ−ル誘導体及び該化合物を含有する抗腫瘍剤 |
DE3462259D1 (de) | 1983-07-22 | 1987-03-05 | Bayer Ag | Substituted furazans |
US4507485A (en) | 1984-01-23 | 1985-03-26 | Bristol-Myers Company | 3,4-Disubstituted-1,2,5-oxadiazoles having histamine H2 -receptor antagonist activity |
JPS60193968A (ja) | 1984-03-13 | 1985-10-02 | Toyo Jozo Co Ltd | シクロペンテン環を有するイミダゾ−ルアミドオキシムおよびその製造法 |
JPS6259283A (ja) | 1985-09-10 | 1987-03-14 | Kaken Pharmaceut Co Ltd | セフアロスポリン化合物 |
JP2696342B2 (ja) | 1988-06-27 | 1998-01-14 | 日本曹達株式会社 | アミジン誘導体、その製造方法及び殺ダニ剤・農園芸用殺菌剤 |
EP0352832B1 (en) | 1988-07-05 | 1992-05-06 | Akzo N.V. | Compounds with bronchodilator activity |
JPH04297449A (ja) | 1991-03-27 | 1992-10-21 | Hokko Chem Ind Co Ltd | N−ヒドロキシベンジルグアニジン誘導体および農園芸用殺菌剤 |
JPH05186458A (ja) | 1991-04-26 | 1993-07-27 | Japan Tobacco Inc | 新規なベンゾピラン誘導体 |
FR2677019B1 (fr) | 1991-05-27 | 1994-11-25 | Pf Medicament | Nouvelles piperidines disubstituees-1,4, leur preparation et leur application en therapeutique. |
JP2709677B2 (ja) | 1992-06-19 | 1998-02-04 | 株式会社大塚製薬工場 | ホスホン酸ジエステル誘導体 |
FR2720396B1 (fr) | 1994-05-27 | 1996-06-28 | Adir | Nouveaux N-pyridyl carboxamides et dérivés leur procédé de préparation et les compositions pharmaceutiques qui les contiennent. |
US5731315A (en) | 1995-06-07 | 1998-03-24 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted sulfonic acid n- (aminoiminomethyl)phenylalkyl!-azaheterocyclamide compounds |
JPH11513679A (ja) | 1995-10-17 | 1999-11-24 | アストラ・フアーマシユウテイカルズ・リミテツド | 薬剤活性キナゾリン化合物 |
WO1997030047A1 (en) | 1996-02-17 | 1997-08-21 | Agrevo Uk Limited | Fungicidal 1,2,4-oxadiazoles and analogues |
US5955495A (en) | 1996-05-03 | 1999-09-21 | Hoffmann-La Roche Inc. | Method of treating diseases of the CNS |
JPH11171702A (ja) | 1997-09-24 | 1999-06-29 | Takeda Chem Ind Ltd | 害虫防除方法 |
US6395876B1 (en) | 1997-12-05 | 2002-05-28 | Medical College Of Georgia Research Institute, Inc. | High-affinity tryptophan transporter |
RO121119B1 (ro) | 1997-12-10 | 2006-12-29 | Dainippon Ink And Chemicals, Inc. | Derivaţi de oximă şi chimicale pentru agricultură, incluzând aceşti derivaţi |
EP1084121B1 (en) | 1998-06-02 | 2002-07-31 | Takeda Chemical Industries, Ltd. | Oxadiazoline derivatives and their use as insecticides |
FR2784678B1 (fr) | 1998-09-23 | 2002-11-29 | Sod Conseils Rech Applic | Nouveaux derives de n-(iminomethyl)amines, leur preparation, leur application a titre de medicaments et les compositions pharmaceutiques les contenant |
AU763030B2 (en) | 1999-03-03 | 2003-07-10 | Samjin Pharmaceutical Co., Ltd. | Piperazine derivatives and process for the preparation thereof |
AU765244B2 (en) | 1999-04-09 | 2003-09-11 | Abbott Gmbh & Co. Kg | Prodrugs of thrombin inhibitors |
BR0011542A (pt) | 1999-05-24 | 2002-03-05 | Mitsubishi Pharma Corp | Compostos de fenoxipropilamina |
JP2001158785A (ja) | 1999-11-30 | 2001-06-12 | Takeda Chem Ind Ltd | 農薬組成物 |
JP2001158786A (ja) | 1999-11-30 | 2001-06-12 | Takeda Chem Ind Ltd | 哺乳動物の外部寄生虫防除剤 |
AU2001239725A1 (en) | 2000-01-13 | 2001-07-24 | Tularik, Inc. | Antibacterial agents |
JP2001233861A (ja) | 2000-02-22 | 2001-08-28 | Ube Ind Ltd | ピラゾールオキシム化合物、その製法及び用途 |
AU1560802A (en) | 2000-06-28 | 2002-01-08 | Smithkline Beecham Plc | Wet milling process |
GB0108102D0 (en) | 2001-03-30 | 2001-05-23 | Pfizer Ltd | Compounds |
EP1444225B1 (en) | 2001-06-18 | 2012-10-10 | Merck Serono SA | Pyrrolidine oxadiazole- and thiadiazole oxime derivatives being oxytocin receptor antagonists. |
US20040127492A1 (en) | 2002-02-19 | 2004-07-01 | Pharmacia Corporation | Cyclic pyrazoles for the inhibition of mitogen activated protein kinase-activated protein kinase-2 |
GB0208224D0 (en) | 2002-04-10 | 2002-05-22 | Celltech R&D Ltd | Chemical compounds |
CA2483451C (en) | 2002-04-12 | 2014-07-29 | Medical College Of Georgia Research Institute, Inc. | Antigen-presenting cell populations and their use as reagents for enhancing or reducing immune tolerance |
JP2005538953A (ja) | 2002-05-28 | 2005-12-22 | 3−ディメンショナル ファーマシューティカルズ, インコーポレイテッド | 新規チオフェンアミジン、それらの組成物、および補体媒介疾患および病気を治療する方法 |
US7157462B2 (en) | 2002-09-24 | 2007-01-02 | Euro-Celtique S.A. | Therapeutic agents useful for treating pain |
US7015321B2 (en) * | 2002-10-12 | 2006-03-21 | The Scripps Research Institute | Synthesis of non-symmetrical sulfamides using burgess-type reagents |
EP2260846B1 (en) | 2003-03-27 | 2018-11-28 | Lankenau Institute for Medical Research | Novel methods for the treatment of cancer |
US7598287B2 (en) | 2003-04-01 | 2009-10-06 | Medical College Of Georgia Research Institute, Inc. | Use of inhibitors of indoleamine-2,3-dioxygenase in combination with other therapeutic modalities |
JP2007512230A (ja) | 2003-08-20 | 2007-05-17 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼ阻害剤として有用な(4−アミノ−1,2,5−オキサジアゾール−4−イル)−ヘテロ芳香族化合物 |
DE10348022A1 (de) | 2003-10-15 | 2005-05-25 | Imtm Gmbh | Neue Dipeptidylpeptidase IV-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen |
DE10348023A1 (de) | 2003-10-15 | 2005-05-19 | Imtm Gmbh | Neue Alanyl-Aminopeptidasen-Inhibitoren zur funktionellen Beeinflussung unterschiedlicher Zellen und zur Behandlung immunologischer, entzündlicher, neuronaler und anderer Erkrankungen |
US7151097B2 (en) * | 2003-11-07 | 2006-12-19 | Pfizer Inc. | Bicyclic pyrazolyl and imidazolyl compounds and uses thereof |
CN101014580B (zh) | 2004-09-08 | 2011-05-04 | 田边三菱制药株式会社 | 吗啉化合物 |
JP5065908B2 (ja) | 2004-12-24 | 2012-11-07 | プロシディオン・リミテッド | Gタンパク質結合受容体作動薬 |
US7429667B2 (en) | 2005-01-20 | 2008-09-30 | Ardea Biosciences, Inc. | Phenylamino isothiazole carboxamidines as MEK inhibitors |
KR101562549B1 (ko) | 2005-05-10 | 2015-10-23 | 인사이트 홀딩스 코포레이션 | 인돌아민 2,3-디옥시게나제의 조절제 및 이의 사용방법 |
WO2006133417A1 (en) | 2005-06-07 | 2006-12-14 | Valeant Pharmaceuticals International | Phenylamino isothiazole carboxamidines as mek inhibitors |
CA2613548A1 (en) | 2005-06-30 | 2007-01-11 | Anthrogenesis Corporation | Repair of tympanic membrane using placenta derived collagen biofabric |
DE102005060466A1 (de) | 2005-12-17 | 2007-06-28 | Bayer Cropscience Ag | Carboxamide |
CA2634198C (en) | 2005-12-20 | 2014-06-03 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
US20070203140A1 (en) | 2006-02-09 | 2007-08-30 | Combs Andrew P | N-hydroxyguanidines as modulators of indoleamine 2,3-dioxygenase |
JP4297449B2 (ja) | 2006-05-12 | 2009-07-15 | 株式会社サクラクレパス | 墨汁 |
CL2007002650A1 (es) | 2006-09-19 | 2008-02-08 | Incyte Corp | Compuestos derivados de heterociclo n-hidroxiamino; composicion farmaceutica, util para tratar cancer, infecciones virales y desordenes neurodegenerativos entre otras. |
WO2008036643A2 (en) | 2006-09-19 | 2008-03-27 | Incyte Corporation | Amidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
WO2008036652A2 (en) | 2006-09-19 | 2008-03-27 | Incyte Corporation | Amidines as modulators of indoleamine 2,3-dioxygenase |
WO2008036642A2 (en) | 2006-09-19 | 2008-03-27 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
WO2008058178A1 (en) * | 2006-11-08 | 2008-05-15 | Incyte Corporation | N-hydroxyamidinoheterocycles as modulators of indoleamine 2,3-dioxygenase |
EP2121621B1 (en) | 2006-12-08 | 2014-05-07 | Exelixis Patent Company LLC | Lxr and fxr modulators |
TW200845991A (en) | 2007-01-12 | 2008-12-01 | Smithkline Beecham Corp | N-substituted glycine derivatives: hydroxylase inhibitors |
JP2011507910A (ja) | 2007-12-21 | 2011-03-10 | ユニバーシティー オブ ロチェスター | 真核生物の寿命を変更するための方法 |
WO2009128521A1 (ja) * | 2008-04-15 | 2009-10-22 | 帝人ファーマ株式会社 | システインプロテアーゼ阻害剤 |
EA029781B1 (ru) | 2008-07-08 | 2018-05-31 | Инсайт Корпорейшн | 1,2,5-оксадиазолы в качестве ингибиторов индоламин-2,3-диоксигеназы |
SI3066085T1 (sl) | 2013-11-08 | 2020-08-31 | Incyte Holdings Corporation | Postopek sinteze inhibitorja indolamina 2,3-dioksigenaze |
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