ME03792B - Postupak sinteze inhibitora indolamin 2,3-dioksigenaze - Google Patents
Postupak sinteze inhibitora indolamin 2,3-dioksigenazeInfo
- Publication number
- ME03792B ME03792B MEP-2020-146A MEP2020146A ME03792B ME 03792 B ME03792 B ME 03792B ME P2020146 A MEP2020146 A ME P2020146A ME 03792 B ME03792 B ME 03792B
- Authority
- ME
- Montenegro
- Prior art keywords
- compound
- formula
- reducing agent
- optionally
- reacting
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims 28
- 230000015572 biosynthetic process Effects 0.000 title 1
- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 title 1
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 title 1
- 239000003112 inhibitor Substances 0.000 title 1
- 238000003786 synthesis reaction Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 53
- 239000003638 chemical reducing agent Substances 0.000 claims 14
- 238000006243 chemical reaction Methods 0.000 claims 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical group CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 claims 8
- -1 9-fluorenylmethyloxycarbonyl Chemical group 0.000 claims 7
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [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
- 125000002924 primary amino group Chemical group [H]N([H])* 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
- 238000010511 deprotection reaction Methods 0.000 claims 5
- 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims 3
- 230000008878 coupling Effects 0.000 claims 3
- 238000010168 coupling process Methods 0.000 claims 3
- 238000005859 coupling reaction Methods 0.000 claims 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims 3
- MBYLVOKEDDQJDY-UHFFFAOYSA-N tris(2-aminoethyl)amine Chemical group NCCN(CCN)CCN MBYLVOKEDDQJDY-UHFFFAOYSA-N 0.000 claims 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 2
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 2
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims 2
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 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
- 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
- 125000003545 alkoxy group Chemical group 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 group 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
- 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
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- 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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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (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)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Indole Compounds (AREA)
Claims (29)
1. Postupak koji obuhvata reagovanje jedinjenja formule F5: sa aldehidom formule F6: pri čemu je Pg1 amino zaštitna grupa, da se dobije jedinjenje formule F7:
2. Postupak prema zahtevu 1, pri čemu je Pg1 : (a) etoksikarbonil, terc-butoksikarbonil, benziloksikarbonil, ili 9-fluorenilmetiloksikarbonil; ili (b) terc-butoksikarbonil.
3. Postupak prema bilo kom zahtevu 1-2, pri čemu se pomenuta reakcija izvodi u prisustvu redukcionog sredstva, gde je pomenuto redukciono sredstvo: (a) borhidridno redukciono sredstvo; ili (b) borhidridno redukciono sredstvo koje je natrijum triacetoksiborhidrid.
4. Postupak prema bilo kom zahtevu 1-3, koji dalje obuhvata uklanjanje zaštite pomenutog jedinjenja formule F7 da se dobije jedinjenje formule F8: opciono gde pomenuto uklanjanje zaštitne grupe uključuje reagovanje jedinjenja formule F7 sa hlorovodoničnom kiselinom.
5. Postupak prema zahtevu 4, koji dalje obuhvata reagovanje pomenutog jedinjenja formule F8, sa Pg2-NH-SO2-X, u prisustvu organske baze da se dobije jedinjenje formule F9: pri čemu: Pg2 je amino zaštitna grupa; i X je halo.
6. Postupak prema zahtevu 5, pri čemu je Pg2 : (a) etoksikarbonil, terc-butoksikarbonil, benziloksikarbonil, ili 9-fluorenilmetiloksikarbonil; ili (b) terc-butoksikarbonil; i pri čemu X je hlor.
7. Postupak prema bilo kom zahtevu 5-6, koji dalje obuhvatai uklanjanje zaštite pomenutog jedinjenja formule F9 da se dobije jedinjenje formule F10: opciono gde pomenuto uklanjanje zaštitne grupe obuhvata reagovanje jedinjenje formule F9 sa hlorovodoničnom kiselinom.
8. Postupak prema zahtevu 7, koji dalje obuhvata reagovanje pomenutog jedinjenja formule F10 sa bazom da se dobije jedinjenje formule I: opciono gde je pomenuta baza natrijum hidroksid.
9. Postupak, koji obuhvata reagovanje jedinjenja formule F15: sa jedinjenjem formule F5: da se dobije jedinjenje formule F16: 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 pomenuti fenil-C1-3 alkil opciono supstituisan sa 1, 2, ili 3 nezavisno izabranih C1-4 alkoksi grupa; i R3 je C1-6 alkil ili benzil.
10. Postupak prema zahtevu 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 kom zahtevu 9-10, pri čemu pomenuta reakcija se izvodi u prisustvu redukcionog sredstva, gde je pomenuto redukciono sredstvo: (a) borhidridno redukciono sredstvo; ili (b) borhidridno redukciono sredstvo koje je natrijum triacetoksiborhidrid; i gde se pomenuta reakcija izvodi u prisustvu trifluorosirćetne kiseline.
12. Postupak prema bilo kom zahtevu 9-11, koji dalje obuhvata uklanjanje zaštite pomenutog jedinjenja formule F16 da se dobije jedinjenje formule F10: pri čemu pomenuto uklanjanje zaštite obuhvata: (a) reagovanje jedinjenja formule F16 sa trifluorosirćetnom kiselinom; ili (b) reagovanje jedinjenja formule F16 sa hlorovodoničnom kiselinom.
13. Postupak prema bilo kom zahtevu 9-12, pri čemu je pomenuto jedinjenje formule F15 dobijeno postupkom koji obuhvata tretiranje jedinjenja formule F14: sa redukcionim sredstvom da se dobije pomenuto jedinjenje formule F15; pri čemu R2 je C1-4 alkil; opciono gde je pomenuto redukciono sredstvo diizobutilaluminijum hidrid.
14. Postupak prema zahtevu 13, pri čemu je pomenuto jedinjenje formule F14 dobijeno postupkom koji obuhvata zaštitu jedinjenja formule F13: sa jednim ili više nezavisno izabranih amino zaštitnih sredstava da se dobije jedinjenje formule F14; opciono gde je pomenuto jedno ili više amino zaštitnih sredstava izabrano od alil bromida i 4-metoksibenzil hlorida, i gde se pomenuta zaštita izvodi u prisustvu baze.
15. Jedinjenje formule F15: pri čemu: R3 je C1-6 alkil ili benzil; i svaki R1 je nezavisno amino zaštitna grupa.
16. Jedinjenje prema zahtevu 15, koje 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 obuhvata reagovanje jedinjenja formule F17: pri čemu R4 je C1-6 alkil, C1-6 haloalkil, benzil, ili 9H-fluoren-9-ilmetil sa jedinjenjem formule F5: da se dobije jedinjenje formule F18:
18. Postupak prema zahtevu 17, pri čemu R4 je: (a) terc-butil; (b) benzil; (c) etil; ili (d) 2,2,2-trihloretil.
19. Postupak prema zahtevu 18, pri čemu se pomenuta reakcija izvodi u prisustvu redukcionog sredstva; opciono gde je pomenuto redukciono sredstvo trietilsilan, i gde se pomenuta reakcija izvodi u prisustvu organske kiseline; opciono gde je pomenuta organska kiselina trifluorosirćetna kiselina.
20. Postupak prema bilo kom zahtevu 18-19, koji dalje obuhvata uklanjanje zaštite pomenutog jedinjenja formule F18 da se dobije jedinjenje formule F10: opciono gde pomenuto uklanjanje zaštitne grupe uključuje reagovanje jedinjenja formule F18 sa cinkom u prisustvu sirćetne kiseline.
21. Postupak prema zahtevu 20, koji dalje obuhvata reagovanje pomenutog jedinjenja formule F10 sa bazom da se dobije jedinjenje formule I: opciono gde je pomenuta baza natrijum hidroksid.
22. Postupak prema zahtevu 17, pri čemu R4 je 9H-fluoren-9-ilmetil.
23. Postupak prema zahtevu 22, pri čemu se pomenuta reakcija izvodi u prisustvu redukcionog sredstva; opciono gde je pomenuto redukciono sredstvo trietilsilan; i gde se pomenuta reakcija izvodi u prisustvu organske kiseline; opciono gde je pomenuta organska kiselina metansulfonska kiselina.
24. Postupak prema bilo kom zahtevu 22-23, koji dalje obuhvata pretvaranje pomenutog jedinjenja formule F18 u jedinjenje formule I: pri čemu pomenuto pretvaranje obuhvata spajanje jedinjenja formule F18 sa bazom da bi se obrazovala prva smeša; opciono gde je pomenuta baza N,N-bis(2-aminoetil)etan-1,2-diamin.
25. Postupak prema zahtevu 24, pri čemu pomenuto pretvaranje dalje obuhvata dodavanje vodene hlorovodonične kiseline u pomenutu prvu smešu.
26. Jedinjenje formule F17: gde je R4 C1-6 haloalkil, benzil, ili 9H-fluoren-9-ilmetil.
27. Jedinjenje prema zahtevu 26, koje je: (a) benzil N-(2,2-dimetoksietil)sulfamoilkarbamat; (b) 2,2,2-trihloretil N-(2,2-dimetoksietil)sulfamoilkarbamat; ili (c) (9H-fluoren-9-il)metil N-(2,2-dimetoksietil)sulfamoilkarbamat.
28. Jedinjenje koje je: (a) terc-butil N-(2,2-dimetoksietil)sulfamoilkarbamat; ili (b) etil N-(2,2-dimetoksietil)sulfamoilkarbamat.
29. Postupak, koji obuhvata:i) reagovanje jedinjenja formule F19:img22 sa jedinjenjem formule F5:img23 u prisustvu trietilsilana i metansulfonske kiseline da se dobije jedinjenje formule F20:img24 iii) pretvaranje pomenutog jedinjenja formule F20 u jedinjenje formule I:img25 gde pomenuto pretvaranje obuhvata spajanje pomenutog jedinjenja formule F20 sa N,N-bis(2-aminoetil)etan-1,2-diaminom. Incyte Holdings Corporation Zastupaju, Postupak, koji obuhvata:i) reagovanje jedinjenja formule F19: sa jedinjenjem formule F5: u prisustvu trietilsilana i metansulfonske kiseline da se dobije jedinjenje formule F20: iii) pretvaranje pomenutog jedinjenja formule F20 u jedinjenje formule I: gde pomenuto pretvaranje obuhvata spajanje pomenutog jedinjenja formule F20 sa N,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 | |
| PCT/US2014/064531 WO2015070007A1 (en) | 2013-11-08 | 2014-11-07 | Process for the synthesis of an indoleamine 2,3-dioxygenase inhibitor |
| EP14812015.7A EP3066085B1 (en) | 2013-11-08 | 2014-11-07 | Process for the synthesis of an indoleamine 2,3-dioxygenase inhibitor |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ME03792B true ME03792B (me) | 2021-04-20 |
Family
ID=52023608
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| MEP-2020-146A ME03792B (me) | 2013-11-08 | 2014-11-07 | Postupak sinteze inhibitora indolamin 2,3-dioksigenaze |
Country Status (33)
| Country | Link |
|---|---|
| US (3) | US9321755B2 (me) |
| EP (2) | EP3066085B1 (me) |
| JP (4) | JP6461953B2 (me) |
| KR (2) | KR102617531B1 (me) |
| CN (2) | CN105899498B (me) |
| AR (1) | AR098343A1 (me) |
| AU (2) | AU2014346647B2 (me) |
| BR (2) | BR122020009912B1 (me) |
| CA (1) | CA2929552C (me) |
| CL (1) | CL2016001082A1 (me) |
| CR (2) | CR20160252A (me) |
| CY (1) | CY1123164T1 (me) |
| DK (1) | DK3066085T3 (me) |
| EA (2) | EA201991770A1 (me) |
| ES (1) | ES2799582T3 (me) |
| HR (1) | HRP20201089T1 (me) |
| HU (1) | HUE049337T2 (me) |
| IL (2) | IL245314B (me) |
| LT (1) | LT3066085T (me) |
| ME (1) | ME03792B (me) |
| MX (2) | MX366874B (me) |
| MY (1) | MY174254A (me) |
| PE (2) | PE20160863A1 (me) |
| PH (2) | PH12019500770B1 (me) |
| PL (1) | PL3066085T3 (me) |
| PT (1) | PT3066085T (me) |
| RS (1) | RS60598B1 (me) |
| SG (2) | SG10201803874PA (me) |
| SI (1) | SI3066085T1 (me) |
| SM (1) | SMT202000381T1 (me) |
| TW (5) | TW202440069A (me) |
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| KR20160108568A (ko) * | 2014-02-04 | 2016-09-19 | 인사이트 코포레이션 | 암을 치료하기 위한 pd-1 길항제 및 ido1 억제제의 조합 |
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| HK1252514A1 (zh) * | 2015-07-14 | 2019-05-31 | Kyowa Kirin Co., Ltd. | 包含与抗体组合施予的ido抑制剂的肿瘤治疗剂 |
| MX2018005600A (es) | 2015-11-04 | 2018-11-09 | Incyte Corp | Composiciones farmaceuticas y metodos para la inhibicion de indolamina 2,3-dioxigenasa e indicaciones para ello. |
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| 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 |
| 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 |
| 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 |
| CN109689652B (zh) | 2016-08-23 | 2022-04-26 | 北京诺诚健华医药科技有限公司 | 稠杂环类衍生物、其制备方法及其在医学上的应用 |
| CN109952300B (zh) | 2016-09-24 | 2022-01-18 | 百济神州有限公司 | 5或8-取代的咪唑并[1,5-a]吡啶 |
| US11168078B2 (en) * | 2016-11-28 | 2021-11-09 | Shanghai Fochon Pharmaceutical Co., Ltd. | Sulfoximine, sulfonimidamide, sulfondiimine and diimidosulfonamide compounds as inhibitors of indoleamine 2,3-dioxygenase |
| EP3559009B1 (en) | 2016-12-22 | 2021-04-07 | Calithera Biosciences, Inc. | Compositions and methods for inhibiting arginase activity |
| 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 |
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| 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 |
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