HRP20130906T1 - Postupci i intermedijeri za pripravu makrocikliäśkog inhibitora hcv proteaze - Google Patents
Postupci i intermedijeri za pripravu makrocikliäśkog inhibitora hcv proteaze Download PDFInfo
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- HRP20130906T1 HRP20130906T1 HRP20130906AT HRP20130906T HRP20130906T1 HR P20130906 T1 HRP20130906 T1 HR P20130906T1 HR P20130906A T HRP20130906A T HR P20130906AT HR P20130906 T HRP20130906 T HR P20130906T HR P20130906 T1 HRP20130906 T1 HR P20130906T1
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- Prior art keywords
- compound
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- solvent
- salt
- cinchonidine
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- 238000000034 method Methods 0.000 title claims 32
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 title 1
- 239000000543 intermediate Substances 0.000 title 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 16
- KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical compound C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 claims 11
- 239000002904 solvent Substances 0.000 claims 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 9
- 150000003839 salts Chemical class 0.000 claims 8
- 238000006243 chemical reaction Methods 0.000 claims 7
- 239000000203 mixture Substances 0.000 claims 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
- -1 bicyclic lactone amide Chemical class 0.000 claims 6
- 150000001408 amides Chemical class 0.000 claims 5
- KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 claims 5
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- 239000003153 chemical reaction reagent Substances 0.000 claims 3
- 239000011877 solvent mixture Substances 0.000 claims 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 3
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 2
- 239000004215 Carbon black (E152) Substances 0.000 claims 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims 2
- GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 claims 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- 150000001298 alcohols Chemical class 0.000 claims 2
- 239000000010 aprotic solvent Substances 0.000 claims 2
- 239000003054 catalyst Substances 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
- 239000003759 ester based solvent Substances 0.000 claims 2
- 150000002170 ethers Chemical class 0.000 claims 2
- 229930195733 hydrocarbon Natural products 0.000 claims 2
- 150000002430 hydrocarbons Chemical class 0.000 claims 2
- 238000001953 recrystallisation Methods 0.000 claims 2
- 239000000725 suspension Substances 0.000 claims 2
- 150000003512 tertiary amines Chemical class 0.000 claims 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical group C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims 1
- 239000007821 HATU Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 238000002425 crystallisation Methods 0.000 claims 1
- 230000008025 crystallization Effects 0.000 claims 1
- 150000008282 halocarbons Chemical class 0.000 claims 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims 1
- 239000012442 inert solvent Substances 0.000 claims 1
- 125000000686 lactone group Chemical group 0.000 claims 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- QLSTWGZDXAHREY-UHFFFAOYSA-N n-methylhex-1-en-1-amine Chemical compound CCCCC=CNC QLSTWGZDXAHREY-UHFFFAOYSA-N 0.000 claims 1
- UGLYZKRVGNAOLZ-UHFFFAOYSA-N propan-2-yl 2-propan-2-yloxy-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)C)C(OC(C)C)C=CC2=C1 UGLYZKRVGNAOLZ-UHFFFAOYSA-N 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/475—Preparation of carboxylic acid esters by splitting of carbon-to-carbon bonds and redistribution, e.g. disproportionation or migration of groups between different molecules
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/40—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
- C07D453/04—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Virology (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Furan Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Claims (29)
1. Postupak za dobivanje spoja sa formulom (VIII), koji započinje od soli kinkonidina (XXa), koja reagira sa N-metil-heksenaminom (NMHA) (XIX) u reakciji kojom nastaje amid da se dobije biciklički laktonski amid (XVIII), u kojem je laktonska skupina otvorena, da se dobije željeni produkt (VIII), kako je prikazano u dolje navedenoj shemi, pri čemu R1 je C1-4alkil:
[image]
2. Postupak prema zahtjevu 1 naznačen time da R1 je metil.
3. Postupak prema zahtjevima 1 ili 2, naznačen time da se reakcija kojom nastaje amid provodi u prisutnosti reagensa za spajanje amida u reakcijski inertnom otapalu.
4. Postupak prema zahtjevu 3, naznačen time da se reakcija provodi u prisutnosti baze.
5. Postupak prema zahtjevu 3 ili zahtjevu 4 naznačen time da otapalo sadrži halogenirane ugljikovodike, etere, alkohole, ugljikovodikova otapala, bipolarna aprotična otapala, ili njihove smjese.
6. Postupak prema zahtjevu 5 naznačen time da su halogenirana otapala diklorometan (DCM) ili kloroform, eteri su tetrahidrofuran (THF) ili 2-metiltetrahidrofuran (MeTHF), alkoholi su metanol ili etanol, ugljikovodikova otapala su toluen ili ksilen, a bipolarna aprotična otapala su DMF, DMA ili acetonitril.
7. Postupak prema zahtjevu 3 ili zahtjevu 4 naznačen time da reagens za spajanje amida sadrži slijedeća sredstva N-etoksikarbonil-2-etoksi-1,2-dihidrokinolin (EEDQ), N-izopropoksikarbonil-2-izopropoksi-1,2-dihidrokinolin (IIDQ), N,N,N',N'-tetrametil-O-(7-azabenzotriazol-1-il)uronij heksafluorofosfat (HATU), benzotriazol-1-il-oksi-tris-pirolidino-fosfonij heksafluorofosfat, CDI, 1-etil-3-(3-dimetilaminopropil) karbodiimid (EDCI) ili njegov hidroklorid, dicikloheksilkarbodiimid (DCC), 1,3-diizopropilkarbodiimid, ili O-benzotriazol-N,N,N',N'-tetrametil-uronij-heksafluorofosfat (HBTU).
8. Postupak prema zahtjevu 7 naznačen time da je reagens za spajanje amida u prisutnosti katalizatora.
9. Postupak prema zahtjevu 8 naznačen time da katalizator je 1-hidroksibenzotriazol (HOBt) ili 4-dimetilaminopiridin (DMAP).
10. Postupak prema zahtjevu 4 naznačen time da baza je tercijarni amin.
11. Postupak prema zahtjevu 10, naznačen time da tercijarni amin je trietilamin, N-metilmorfolin, N,N-diizopropiletilamin.
12. Postupak za dobivanje soli kinkonidina (XXa), koja se dobiva iz racemske soli (XX) pomoću kristalizacije:
[image]
13. Postupak prema zahtjevu 12, naznačen time da se racemska sol (XX) dobiva pomoću kontakta bicikličke laktonske karboksilne kiseline (XV) sa kinkonidinom:
[image]
14. Postupak prema zahtjevu 13, naznačen time da se suspenzija kinkonidina dodaje u otopinu (XV) kod temperature od oko 50 do oko 70°C i potom se smjesa ostavlja da se ohladi, poslije čega kristalizira željeni proizvod (XXa).
15. Postupak prema zahtjevu 13, naznačen time da je (XV) otopljen u otapalu koje je odabrano od esterskih otapala, te otapala za suspenziju kinkonidina uključuju acetonitril.
16. Postupak prema zahtjevu 15, naznačen time da esterska otapala su etil acetat.
17. Postupak prema zahtjevima 14 ili 15, naznačen time da se formiranje soli provodi kod temperature od oko 60°C, te je smjesa ostavljena da se ohladi približno do temperature okoline.
18. Postupak prema zahtjevu 17, naznačen time da je smjesa ostavljena da se ohladi do temperature u rasponu od oko 20 do oko 25°C.
19. Postupak prema zahtjevima 14 ili 15, naznačen time da se sol nadalje pročišćava sa rekristalizacijom od prikladnog otapala ili smjese otapala; ili pomoću ponovnog miješanja sa otapalom ili smjesom otapala.
20. Postupak prema zahtjevu 19, naznačen time da otapalo u rekristalizaciji je C1-4alkanol, ili kod ponovnog miješanja otapalo ili smjesa otapala je smjesa etanol/voda.
21. Postupak prema zahtjevu 20, naznačen time da C1-4alkanol je izopropanol i/ili smjesa etanol/voda sa omjerom 5%/95% (tež./tež.) smjese voda/etanol.
22. Sol kinkonidina naznačena time da ima formulu
[image]
23. Uporaba soli kinkonidina (XXa) definirane u zahtjevu 22, naznačena time da se koristi kao intermedijer za dobivanje intermedijera (VIII).
24. Postupak za dobivanje spoja sa formulom (I)
[image]
naznačen time da se navedeni postupak sastoji od postupka za dobivanje spoja sa formulom (VIII) prema bilo kojem zahtjevu od 1 do 11, te potom slijedi konverzija u spoj sa formulom (I).
25. Postupak prema zahtjevu 24, naznačen time da se konverzija u spoj sa formulom (I) provodi kako slijedi:
(i) reakcijom spoja sa formulom (VIII) sa spojem sa formulom (VII) da se dobije spoj sa formulom (VI),
[image]
(ii) konverzijom (VI) u (I) u skladu sa slijedećom shemom:
[image]
[image]
26. Postupak za dobivanje spoja sa formulom (I), kako je definirano u zahtjevu 24, naznačen time da navedeni postupak sadrži postupak za dobivanje spoja sa formulom (XXa) prema bilo kojem zahtjevu od 12 do 21, te potom slijedi konverzija u spoj sa formulom (I).
27. Postupak prema zahtjevu 26, naznačen time da se spoj sa formulom (XXa) prvo pretvara u spoj sa formulom (VIII) prateći postupak prema bilo kojem zahtjevu od 1 do 11.
28. Postupak prema zahtjevu 27, naznačen time da je konverzija od spoja sa formulom (VIII) u spoj sa formulom (I) kako je zatraženo u zahtjevu 25.
29. Uporaba soli kinkonidina (XXa) definirane u zahtjevu 22, naznačena time da se koristi kao intermedijer za dobivanje spoja (I) kako je definirano u zahtjevu 24.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP08172691 | 2008-12-23 | ||
| PCT/EP2009/067715 WO2010072742A1 (en) | 2008-12-23 | 2009-12-22 | Processes and intermediates for preparing a macrocyclic protease inhibitor of hcv |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20130906T1 true HRP20130906T1 (hr) | 2013-10-25 |
Family
ID=40548041
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20130906AT HRP20130906T1 (hr) | 2008-12-23 | 2013-09-24 | Postupci i intermedijeri za pripravu makrocikliäśkog inhibitora hcv proteaze |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US8927722B2 (hr) |
| EP (1) | EP2382198B1 (hr) |
| JP (1) | JP5687631B2 (hr) |
| KR (1) | KR101734507B1 (hr) |
| CN (1) | CN102264715B (hr) |
| AR (1) | AR074863A1 (hr) |
| AU (1) | AU2009331530B2 (hr) |
| BR (1) | BRPI0923393B1 (hr) |
| CA (1) | CA2745565C (hr) |
| CY (1) | CY1114488T1 (hr) |
| DK (1) | DK2382198T3 (hr) |
| ES (1) | ES2429013T3 (hr) |
| HK (1) | HK1164839A1 (hr) |
| HR (1) | HRP20130906T1 (hr) |
| IL (1) | IL213246A (hr) |
| MX (1) | MX2011006764A (hr) |
| PL (1) | PL2382198T3 (hr) |
| PT (1) | PT2382198E (hr) |
| RU (1) | RU2016120007A (hr) |
| SI (1) | SI2382198T1 (hr) |
| SM (1) | SMT201300116B (hr) |
| TW (1) | TWI461424B (hr) |
| WO (1) | WO2010072742A1 (hr) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2016120007A (ru) | 2008-12-23 | 2018-11-13 | Орто-Макнейл-Янссен Фармасьютикалз, Инк | Способы и промежуточные соединения для получения макроциклического ингибитора протеазы вируса гепатита c |
| BR112014006984A2 (pt) * | 2011-09-22 | 2017-04-04 | Janssen Pharmaceuticals Inc | processos e intermediários para a preparação de um inibidor macrocíclico de proteases do hcv |
| CA2848377A1 (en) * | 2011-10-28 | 2013-05-02 | Janssen Pharmaceuticals, Inc. | Improved process for preparing an intermediate of the macrocyclic protease inhibitor tmc 435 |
| CN103387509B (zh) * | 2012-05-11 | 2016-06-08 | 重庆博腾制药科技股份有限公司 | 一种hcv蛋白酶抑制剂中间体的制备方法 |
| BR112014030649A2 (pt) | 2012-06-08 | 2017-06-27 | Gilead Sciences Inc | inibidores macrocíclicos da flaviviridae vírus |
| WO2013185103A1 (en) | 2012-06-08 | 2013-12-12 | Gilead Sciences, Inc. | Macrocyclic inhibitors of flaviviridae viruses |
| AR091279A1 (es) | 2012-06-08 | 2015-01-21 | Gilead Sciences Inc | Inhibidores macrociclicos de virus flaviviridae |
| UA119315C2 (uk) | 2012-07-03 | 2019-06-10 | Гіліад Фармассет Елелсі | Інгібітори вірусу гепатиту с |
| WO2014145095A1 (en) | 2013-03-15 | 2014-09-18 | Gilead Sciences, Inc. | Macrocyclic and bicyclic inhibitors of hepatitis c virus |
| CN105308043B (zh) * | 2014-05-29 | 2018-01-30 | 杭州普晒医药科技有限公司 | 丙型肝炎药物的晶型及其制备方法、其药物组合物和用途 |
| MA41812A (fr) | 2015-03-27 | 2018-01-30 | Janssen Pharmaceuticals Inc | Procédés et intermédiaires pour la préparation d'un inhibiteur de protéase macrocyclique du vhc |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL8300536A (nl) * | 1983-02-14 | 1984-09-03 | Oce Andeno Bv | Optisch actief alfa-azido-p-hydroxyfenylazijnzuur en zijn zouten alsmede de bereiding daarvan. |
| JPS6124539A (ja) * | 1984-07-11 | 1986-02-03 | Sagami Chem Res Center | 光学活性（ｒ）−２，５，１２−トリヒドロキシ−１，２，３，４−テトラヒドロナフタセン−６，１１−ジオン−２−カルボン酸の取得方法 |
| JP4218040B2 (ja) * | 1997-12-26 | 2009-02-04 | 曽田香料株式会社 | 有機酸とアミンの複合塩の製造法 |
| JP3844112B2 (ja) | 2000-08-23 | 2006-11-08 | 高砂香料工業株式会社 | ３，５，６−トリヒドロキシヘキサン酸アンモニウム塩誘導体、及びその製造方法 |
| NZ548739A (en) | 2004-01-30 | 2010-10-29 | Medivir Ab | HCV NS-3 Serine protease inhibitors |
| CN101146794A (zh) | 2005-01-21 | 2008-03-19 | 阿斯泰克斯治疗有限公司 | 用于抑制cdk和gsk的吡唑衍生物 |
| PE20070211A1 (es) * | 2005-07-29 | 2007-05-12 | Medivir Ab | Compuestos macrociclicos como inhibidores del virus de hepatitis c |
| MY139988A (en) * | 2005-07-29 | 2009-11-30 | Tibotec Pharm Ltd | Macrocylic inhibitors of hepatitis c virus |
| PT2121674E (pt) * | 2007-02-01 | 2010-09-03 | Tibotec Pharm Ltd | Processos e intermediários para a preparação de um inibidor macrocíclico da protease do hcv |
| CN101627020B (zh) * | 2007-02-08 | 2015-06-17 | 泰博特克药品有限公司 | 抑制hcv的大环苯基氨基甲酸酯 |
| RU2016120007A (ru) | 2008-12-23 | 2018-11-13 | Орто-Макнейл-Янссен Фармасьютикалз, Инк | Способы и промежуточные соединения для получения макроциклического ингибитора протеазы вируса гепатита c |
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2009
- 2009-12-22 RU RU2016120007A patent/RU2016120007A/ru not_active Application Discontinuation
- 2009-12-22 SI SI200930731T patent/SI2382198T1/sl unknown
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- 2009-12-22 BR BRPI0923393-8A patent/BRPI0923393B1/pt not_active IP Right Cessation
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