DK2970263T3 - Processer til tilvirkning af et apoptose-foranledigende virkemiddel - Google Patents
Processer til tilvirkning af et apoptose-foranledigende virkemiddel Download PDFInfo
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- DK2970263T3 DK2970263T3 DK14715501.4T DK14715501T DK2970263T3 DK 2970263 T3 DK2970263 T3 DK 2970263T3 DK 14715501 T DK14715501 T DK 14715501T DK 2970263 T3 DK2970263 T3 DK 2970263T3
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- IPRZKPSZGFFWEI-MRVPVSSYSA-N (1S)-1-methyl-4-(nitromethyl)cyclohex-3-en-1-ol Chemical compound C[C@]1(CC=C(CC1)C[N+](=O)[O-])O IPRZKPSZGFFWEI-MRVPVSSYSA-N 0.000 description 1
- FGXQQTSLFAVOCN-UHFFFAOYSA-N 1,4-dioxaspiro[4.5]decan-6-one Chemical compound O=C1CCCCC11OCCO1 FGXQQTSLFAVOCN-UHFFFAOYSA-N 0.000 description 1
- KISZDCHFJKYNFW-UHFFFAOYSA-N 1-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazine;dihydrochloride Chemical compound Cl.Cl.C=1C=C(Cl)C=CC=1C=1CC(C)(C)CCC=1CN1CCNCC1 KISZDCHFJKYNFW-UHFFFAOYSA-N 0.000 description 1
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- OPVMBGKPGCGHOW-UHFFFAOYSA-N 2-chloro-4,4-dimethylcyclohexane-1-carbaldehyde Chemical compound CC1(C)CCC(C=O)C(Cl)C1 OPVMBGKPGCGHOW-UHFFFAOYSA-N 0.000 description 1
- BSXRPCFOXBDGBC-UHFFFAOYSA-N 2-chloro-4,4-dimethylcyclohexene-1-carbaldehyde Chemical compound CC1(C)CCC(C=O)=C(Cl)C1 BSXRPCFOXBDGBC-UHFFFAOYSA-N 0.000 description 1
- ZVJQBBYAVPAFLX-UHFFFAOYSA-N 3,3-dimethylcyclohexan-1-one Chemical compound CC1(C)CCCC(=O)C1 ZVJQBBYAVPAFLX-UHFFFAOYSA-N 0.000 description 1
- HNQRHNYBVWICKB-UHFFFAOYSA-N 3-nitro-4-(oxan-4-ylmethylamino)benzenesulfonamide Chemical compound [O-][N+](=O)C1=CC(S(=O)(=O)N)=CC=C1NCC1CCOCC1 HNQRHNYBVWICKB-UHFFFAOYSA-N 0.000 description 1
- DMRMYQUGHOAQFW-UHFFFAOYSA-N 4-[4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazin-1-yl]-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzoic acid Chemical compound C1C(C)(C)CCC(CN2CCN(CC2)C=2C=C(OC=3C=C4C=CNC4=NC=3)C(C(O)=O)=CC=2)=C1C1=CC=C(Cl)C=C1 DMRMYQUGHOAQFW-UHFFFAOYSA-N 0.000 description 1
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- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
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- 238000010268 HPLC based assay Methods 0.000 description 1
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- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-O Methylammonium ion Chemical compound [NH3+]C BAVYZALUXZFZLV-UHFFFAOYSA-O 0.000 description 1
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- 239000007832 Na2SO4 Substances 0.000 description 1
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N Pd(PPh3)4 Substances [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
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- 230000002378 acidificating effect Effects 0.000 description 1
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- 239000000538 analytical sample Substances 0.000 description 1
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- 238000005859 coupling reaction Methods 0.000 description 1
- 238000006880 cross-coupling reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 229910052805 deuterium Inorganic materials 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 150000004795 grignard reagents Chemical class 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 238000001511 high performance liquid chromatography nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 230000001613 neoplastic effect Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 235000011118 potassium hydroxide Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000006268 reductive amination reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- ZGQXNVGCEUEJOC-UHFFFAOYSA-N tert-butyl 4-[[2-(4-chlorophenyl)-4,4-dimethylcyclohexen-1-yl]methyl]piperazine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCN1CC1=C(C=2C=CC(Cl)=CC=2)CC(C)(C)CC1 ZGQXNVGCEUEJOC-UHFFFAOYSA-N 0.000 description 1
- QTUZSJSEZUZNAS-UHFFFAOYSA-N tert-butyl 4-bromo-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(Br)C=C1OC1=CN=C(NC=C2)C2=C1 QTUZSJSEZUZNAS-UHFFFAOYSA-N 0.000 description 1
- 125000004954 trialkylamino group Chemical group 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/45—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation
- C07C45/455—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by condensation with carboxylic acids or their derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
- C07C45/68—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C47/00—Compounds having —CHO groups
- C07C47/38—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings
- C07C47/457—Unsaturated compounds having —CHO groups bound to carbon atoms of rings other than six—membered aromatic rings containing halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Plural Heterocyclic Compounds (AREA)
- Health & Medical Sciences (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
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Claims (24)
- 1. Proces til tilvirkning af en sammensætning af formel Al: Hi\r% V -Q cr (Ai), o hvori R er valgt fra o ,som omfatter: (a) at kombinere en sammensætning af formel (K): co2R N c: N (K) hvori R er Ci til C12 alkyl, med et tert-butoxid salt, et aprotisk organisk opløsningsmiddel og vand til at tilvejebringe en sammensætning af formel (L): co2h c": N Cl^ (L); og(b") at kombinere sammensætningen af formel (L) med l-methyl-3-(3-dimethylaminopropyl)carbodiimid hydrochlorid, 4-dimethylaminopyridin, et organisk opløsningsmiddel, og enten en sammensætning af formel (N) til at tilvejebringe en sammensætning af o formel (Al), hvori R er O no2h ,ιΑ'λ nh2 < J cr (N) eller en sammensætning af formel (P) til at tilvejebringe en sammensætning af o formel (Al), hvori R er aH no2 Η2Ν-έ^ΗΝΗ /-a oh 0 \-Τ"' (P); idet der derved tilvejebringes en sammensætning af formel (Al); hvorved sammensætningen af formel (K) bliver tilvirket ved: (d) at kombinere en sammensætning af formel (D): CO2R Br M (D) med en sammensætning af formel (I): H Λ 2HCI ci·^ (I), en kilde til palladium, et tert-butoxid salt, og en phosphin ligand i et aprotisk organisk opløsningsmiddel til at tilvejebringe sammensætningen af formel (K). o
- 2. Proces ifølge krav 1, hvorved R erχ>og trin (b") omfatter: (b") at kombinere sammensætningen af formel (L) med l-ethyl-3-(3-dimethylaminopropyl)carbodiimid hydrochlorid, 4-dimethylaminopyridin, et organisk opløsningsmiddel og sammensætningen af formel (N): NO2h nh2 k > ° (N); for at tilvejebringe en sammensætning af formel (Al). o
- 3. Proces ifølge krav 1, hvorved R er +o ? og processen yderligere omfatter: (c") at kombinere en sammensætning af formel (M): NO2 νά'01 NH2 (M) med en tertiær amin base, et organisk opløsningsmiddel og (tetrahydro-2H-pyran-4-yl)methanamin eller et salt deraf for at tilvejebringe sammensætningen af formel (N). o
- 4. Proces ifølge krav 1, hvorved R er ΟΉog processen yderligere omfatter: (c") at kombinere en sammensætning af formel (M):no2 NH2 (M) med en tertiær amin base, et organisk opløsningsmiddel og (lR,4R)-4-(aminomethyl)-l-methylcyclohexanol eller et salt deraf til at tilvejebringe sammensætningen af formel (P).
- 5. Proces ifølge et hvilket som helst af kravene 1-4, hvorved tert-butoxid saltet i trin (a) bliver valgt fra gruppen, der består af natrium tert-butoxid and kalium tert-butoxid.
- 6. Proces ifølge et hvilket som helst af kravene 3-5, hvorved den tertiære amin base i trin (c") er N,N-diisopropylethylamin.
- 7. Proces ifølge et hvilket som helst af kravene 1 til 6, hvorved sammensætningen fra formel (I) bliver kombineret med en base forud for kombinationen fra trin (d).
- 8. Proces ifølge et hvilket som helst af kravene 1 til 6 og krav 7, hvorved kilden til palladium i trin (d) er Pd2dba3 eller [(cinnamyl)PdCl]2.
- 9. Proces ifølge et hvilket som helst af kravene 1 til 6, 7 og 8, hvorved phosphin liganden fra trin (d) er en sammensætning af formel (J): >LpJ< Φ ΝΜθ2 (J).
- 10. Proces ifølge et hvilket som helst af kravene 1 til 6, 7, 8 og 9, hvorved kilden til palladium er Pd2dba3, der bliver benyttet en katalytisk mængde af Pd2dba3 i forhold til mængden af sammensætning (I), og hvorved den katalytiske mængde af Pd2dba3 er fra omkring 0,5 molprocent til omkring 2 molprocent.
- 11. Proces ifølge krav 10, hvorved der bliver benyttet en katalytisk mængde af sammensætningen af formel (J) i forhold til mængden af sammensætningen (I), og hvorved den katalytiske mængde af sammensætningen af formel (J) er fra omkring 1 molprocent til omkring 5 molprocent.
- 12. Proces ifølge et hvilket som helst af kravene 1-11, hvorved tert-butoxid saltet i trin (d) bliver valgt fra gruppen, der består af natrium tert-butoxid and kalium tert-butoxid.
- 13. Proces ifølge et hvilket som helst af kravene 1 - 12, hvorved processen yderligere omfatter: (e) at kombinere en sammensætning af formel (B) med en sammensætning af formel (C): co2r C Η (B) Br (C) og et tert-butoxid salt i et organisk opløsningsmiddel til at tilvejebringe sammensætningen af formel (D).
- 14. Proces ifølge krav 13, hvorved tert-butoxid saltet i trin (e) bliver valgt fra gruppen, der består af natrium tert-butoxid and kalium tert-butoxid.
- 15. Proces ifølge krav 13 eller 14, hvorved processen yderligere omfatter: (f) at kombinere en sammensætning af formel (A): Br(A) med R?MgX i et aprotisk organisk opløsningsmiddel; hvorved R1 er Ci til C6 alkyl og X er Cl, Br eller I; (g) at kombinere en Ci til C12 alkyl chloroformat eller en di-(Ci til C12 alkyljdicarbonat med produktet fra trin (f) for at tilvejebringe sammensætningen af formel (C).
- 16. Proces ifølge krav 15, hvorved R1 er isopropyl i trin (f).
- 17. Proces ifølge krav 15 eller 16, hvorved R er tert-butyl i trin (f), og di-(Ci til C12 alkyljdicarbonaten er di-tert-butyl dicarbonat.
- 18. Proces ifølge et hvilket som helst af kravene 1 - 17, hvorved processen yderligere omfatter: (h) at kombinere en sammensætning af formel (E):0<^<'(E)med dimethylformamid og POCI3 for at tilvejebringe en sammensætning af formel (F): O ba (F); (i) at kombinere sammensætningen af formel (F) med en kilde til palladium og 4-chlorophenylboronsyre i et organisk opløsningsmiddel for at tilvejebringe en sammensætning af formel (G): O CiX^^ (G). (j) at kombinere sammensætningen af formel (G) med BOC-piperazin og natrium triacetoxyborohydrid i et organisk opløsningsmiddel for at tilvejebringe en sammensætning af formel (H): Boc 0 (H); og (k) at kombinere sammensætningen af formel (H) med saltsyre for at tilvejebringe sammensætningen af formel (I).
- 19. Proces ifølge krav 18, hvorved kilden til palladium i trin (i) er Pd(OAc)2.
- 20. Proces ifølge krav 18 eller 19, hvorved trin (i) omfatter at kombinere tetrabutylammonium bromid med sammensætningen af formel (F), kilden til palladium og 4-chlorophenylboronsyre i det organiske opløsningsmiddel.
- 21. Proces ifølge et hvilket som helst af kravene 18 - 20, hvorved trin (j) yderligere omfatter at fremstille sammensætningen af formel (H) som et krystallinsk, fast stof.
- 22. Proces ifølge et hvilket som helst af kravene 18 - 21, hvorved trin (k) yderligere omfatter at fremstille sammensætningen af formel (I) som et krystallinsk, fast stof.
- 23. Proces ifølge et hvilket som helst af kravene 1 - 22, hvorved R er valgt fra gruppen, der består af methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl og neo-butyl.
- 24. Proces ifølge et hvilket som helst af kravene 23, hvorved R er tert-butyl.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361780621P | 2013-03-13 | 2013-03-13 | |
| US201461947850P | 2014-03-04 | 2014-03-04 | |
| PCT/US2014/024224 WO2014165044A1 (en) | 2013-03-13 | 2014-03-12 | Processes for the preparation of an apoptosis-inducing agent |
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| Publication Number | Publication Date |
|---|---|
| DK2970263T3 true DK2970263T3 (da) | 2018-08-13 |
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| CN104370905B (zh) * | 2014-10-22 | 2016-06-01 | 南京友杰医药科技有限公司 | Bcl-2抑制剂ABT-199的合成 |
| WO2017156398A1 (en) | 2016-03-10 | 2017-09-14 | Assia Chemical Industries Ltd. | Solid state forms of venetoclax and processes for preparation of venetoclax |
| CN107089981A (zh) * | 2017-04-24 | 2017-08-25 | 杭州科耀医药科技有限公司 | 一种BCL‑2抑制剂Venetoclax的合成方法 |
| MX2020002032A (es) | 2017-08-23 | 2020-09-17 | Guangzhou Lupeng Pharmaceutical Company Ltd | Inhibidores de bcl-2. |
| CN108037196B (zh) * | 2017-11-23 | 2020-06-23 | 中山奕安泰医药科技有限公司 | 一种3-硝基-4-[[(四氢-2h-吡喃-4-基)甲基]氨基]苯磺酰胺的检测方法 |
| IL316472A (en) | 2018-01-10 | 2024-12-01 | Recurium Ip Holdings Llc | Benzamide compounds |
| WO2020003272A1 (en) | 2018-06-29 | 2020-01-02 | Fresenius Kabi Oncology Ltd. | An improved process for the preparation of venetoclax |
| CN108997333A (zh) * | 2018-07-04 | 2018-12-14 | 江苏中邦制药有限公司 | 一种b细胞淋巴瘤因子-2抑制剂abt-199的制备方法 |
| WO2020023435A1 (en) | 2018-07-24 | 2020-01-30 | Albany Molecular Research, Inc. | Venetoclax basic salts and processes for the purification of venetoclax |
| US11903950B2 (en) | 2018-08-22 | 2024-02-20 | Newave Pharmaceutical Inc. | BCL-2 inhibitors |
| WO2020049599A1 (en) * | 2018-09-07 | 2020-03-12 | Msn Laboratories Private Limited, R&D Center | Process for the preparation of 4-(4-{[2-(4-chlorophenyl)-4,4-dimethylcyclohex-1-en-1- yl]methyl}piperazin-1-yl)-n-({3-nitro-4-[(tetrahydro-2h-pyran-4-ylmethyl)amino] phenyl}sulfonyl)-2-(1h-pyrrolo[2,3-b]pyridin-5-yloxy)benzamide) |
| WO2020140005A2 (en) | 2018-12-29 | 2020-07-02 | Newave Pharmaceutical Inc. | Bcl-2 inhibitors |
| US12552784B2 (en) | 2019-12-27 | 2026-02-17 | Newave Pharmaceutical Inc. | 1H-pyrrolo[2,3-b]pyridine derivatives as BCL-2 inhibitors for the treatment of neoplastic and autoimmune diseases |
| CN112079795B (zh) * | 2020-09-16 | 2022-12-09 | 广东莱佛士制药技术有限公司 | 一种维奈托克中间体及其类似物的合成方法 |
| IT202100025976A1 (it) | 2021-10-06 | 2023-04-06 | Univ Degli Studi Di Perugia | Combinazione di principi attivi per il trattamento della leucemia acuta mieloide (LAM) con mutazione della nucleofosmina (NPM1) |
| CN114163369A (zh) * | 2021-12-17 | 2022-03-11 | 武汉工程大学 | 一种含硫/氧酯基芳烃化合物的制备方法 |
| CN116496239A (zh) * | 2022-12-14 | 2023-07-28 | 南京哈柏医药科技有限公司 | 一种维奈托克关键中间体及原料药的合成方法 |
| EP4421075A1 (en) | 2023-02-27 | 2024-08-28 | KRKA, d.d., Novo mesto | Process for the preparation of venetoclax and intermediates used therein |
| IT202400014839A1 (it) | 2024-06-27 | 2025-12-27 | Olon Spa | Processo per preparare venetoclax e relativo intermedio. |
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| KR101278522B1 (ko) | 2004-12-02 | 2013-06-25 | 다이이찌 산쿄 가부시키가이샤 | 7원환 화합물 및 그 제조법 및 의약 용도 |
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| US8546399B2 (en) * | 2009-05-26 | 2013-10-01 | Abbvie Inc. | Apoptosis inducing agents for the treatment of cancer and immune and autoimmune diseases |
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| CN102030651A (zh) * | 2009-09-28 | 2011-04-27 | 莱阳市盛华科技有限公司 | 2-氟-4-溴联苯基甲酸乙酯的合成方法 |
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| KR20180059560A (ko) | 2010-10-29 | 2018-06-04 | 애브비 인코포레이티드 | 아폽토시스―유도제를 포함하는 고체 분산체 |
| RU2593231C2 (ru) | 2010-11-23 | 2016-08-10 | ЭббВи Айэленд Анлимитед Компани | Способы лечения с использованием селективных ингибиторов bcl-2 |
| WO2012071336A1 (en) | 2010-11-23 | 2012-05-31 | Abbott Laboratories | Salts and crystalline forms of an apoptosis-inducing agent |
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