HRP20230002T1 - Postupci pripreme citotoksičnih derivata benzodiazepina - Google Patents
Postupci pripreme citotoksičnih derivata benzodiazepina Download PDFInfo
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- HRP20230002T1 HRP20230002T1 HRP20230002TT HRP20230002T HRP20230002T1 HR P20230002 T1 HRP20230002 T1 HR P20230002T1 HR P20230002T T HRP20230002T T HR P20230002TT HR P20230002 T HRP20230002 T HR P20230002T HR P20230002 T1 HRP20230002 T1 HR P20230002T1
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- 238000000034 method Methods 0.000 title claims 20
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 title 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 title 1
- 231100000433 cytotoxic Toxicity 0.000 title 1
- 230000001472 cytotoxic effect Effects 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims 66
- 150000003839 salts Chemical class 0.000 claims 45
- 238000006243 chemical reaction Methods 0.000 claims 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 9
- 150000002148 esters Chemical class 0.000 claims 9
- 150000004820 halides Chemical class 0.000 claims 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 8
- 125000006244 carboxylic acid protecting group Chemical group 0.000 claims 6
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims 4
- 239000003795 chemical substances by application Substances 0.000 claims 4
- 239000003638 chemical reducing agent Substances 0.000 claims 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 2
- 230000003213 activating effect Effects 0.000 claims 2
- 125000005604 azodicarboxylate group Chemical group 0.000 claims 2
- 239000012351 deprotecting agent Substances 0.000 claims 2
- 238000010511 deprotection reaction Methods 0.000 claims 2
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 claims 2
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 claims 2
- VVWRJUBEIPHGQF-UHFFFAOYSA-N propan-2-yl n-propan-2-yloxycarbonyliminocarbamate Chemical compound CC(C)OC(=O)N=NC(=O)OC(C)C VVWRJUBEIPHGQF-UHFFFAOYSA-N 0.000 claims 2
- QKSQWQOAUQFORH-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylimino]carbamate Chemical compound CC(C)(C)OC(=O)N=NC(=O)OC(C)(C)C QKSQWQOAUQFORH-UHFFFAOYSA-N 0.000 claims 2
- OQJBFFCUFALWQL-UHFFFAOYSA-N n-(piperidine-1-carbonylimino)piperidine-1-carboxamide Chemical compound C1CCCCN1C(=O)N=NC(=O)N1CCCCC1 OQJBFFCUFALWQL-UHFFFAOYSA-N 0.000 claims 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
- C07C205/19—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups bound to carbon atoms of six-membered aromatic rings and hydroxy groups bound to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/16—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C201/00—Preparation of esters of nitric or nitrous acid or of compounds containing nitro or nitroso groups bound to a carbon skeleton
- C07C201/06—Preparation of nitro compounds
- C07C201/12—Preparation of nitro compounds by reactions not involving the formation of nitro groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/44—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members
- C07D207/444—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5
- C07D207/448—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide
- C07D207/452—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having three double bonds between ring members or between ring members and non-ring members having two doubly-bound oxygen atoms directly attached in positions 2 and 5 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms, e.g. maleimide with hydrocarbon radicals, substituted by hetero atoms, directly attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- C07D519/04—Dimeric indole alkaloids, e.g. vincaleucoblastine
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Biophysics (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
Claims (15)
1. Postupak za pripremu spoja formule (A):
[image]
ili njegova sol, koji obuhvaća reakciju spoja formule (V):
[image]
ili njegove soli, sa spojem formule (X):
[image]
pri čemu:
svaka dvostruka linija
[image]
između N i C neovisno predstavlja jednostruku vezu ili dvostruku vezu, pod uvjetom da kada je to dvostruka veza X je odsutan i Y je -H, i kada je to jednostruka veza, X i Y su oba -H; i E je -OH, halid ili -C(=O)E je aktivirani ester.
2. Postupak prema zahtjevu 1, naznačen time što je spoj formule (A) ili njegova sol predstavljen formulom (A-1):
[image]
ili njegova sol, i postupak obuhvaća reakciju spoja formule (V-1):
[image]
ili njegove soli, sa spojem formule (X-1):
[image]
naznačen time što je E -OH, halid ili -C(=O)E je aktivirani ester.
3. Postupak za pripremu spoja formule (A):
[image]
ili njegova sol, koji obuhvaća korake:
1) reakciju spoja formule (IV):
[image]
ili njegove soli, s redukcijskim sredstvom da se dobije spoj formule (V):
[image]
ili njegova sol; i
2) reakciju spoja formule (V) ili njegove soli, sa spojem formule (X):
[image]
pri čemu:
svaka dvostruka linija
[image]
između N i C neovisno predstavlja jednostruku vezu ili dvostruku vezu, pod uvjetom da kada je to dvostruka veza X je odsutan i Y je -H, i kada je to jednostruka veza, X i Y su oba -H; i E je -OH, halid ili -C(=O)E je aktivirani ester.
4. Postupak prema zahtjevu 3, naznačen time što je spoj formule (A) ili njegova sol predstavljen formulom (A-1):
[image]
ili njegova sol, i postupak obuhvaća korake:
1) reakciju spoja formule (IV-1):
[image]
ili njegove soli, s redukcijskim sredstvom da se dobije spoj formule (V-1):
[image]
ili njegova sol; i
2) reakciju spoja formule (V-1) ili njegove sol, sa spojem formule (X-1):
[image]
naznačen time što je E -OH, halid ili -C(=O)E je aktivirani ester.
5. Postupak za pripremu spoja formule (Xa):
[image]
ili njegove soli, koji obuhvaća reakciju spoja formule (IX):
[image]
ili njegova sol, sa sredstvom za uklanjanje zaštite karboksilne kiseline, naznačen time što je P1 zaštitna skupina karboksilne kiseline.
6. Postupak prema zahtjevu 5, naznačen time što je spoj formule (Xa) ili njegova sol predstavljen formulom (X-la):
[image]
ili njegova sol, i postupak obuhvaća reakciju spoja formule (IX-1):
[image]
ili njegove soli, sa sredstvom za uklanjanje zaštite karboksilne kiseline, naznačen time što je P1 zaštitna skupina karboksilne kiseline.
7. Postupak pripreme formule spoja (IX):
[image]
ili njegova sol, koji obuhvaća reakciju spoja formule (VIII):
[image]
ili njegove soli, sa spojem formule (c):
[image]
ili njegova sol, naznačen time što E1 je -OH, halid ili -C(=O)E1 je aktivirani ester; i P1 je zaštitna skupina karboksilne kiseline.
8. Postupak prema zahtjevu 7, naznačen time što je spoj formule (IX) ili njegova sol predstavljen formulom (IX-1):
[image]
ili njegova sol, i postupak obuhvaća reakciju spoja formule (VIII):
[image]
ili njegove soli, sa spojem formule (c-1):
[image]
ili njegova sol, gdje E1 je -OH, halid ili -C(=O)E1 je aktivirani ester; i P1 je zaštitna skupina karboksilne kiseline.
9. Postupak za pripremu spoja formule (Xa):
[image]
ili njegova sol, koji obuhvaća korake:
1) reakciju spoja formule (VIII):
[image]
ili njegove soli, sa spojem formule (c):
[image]
ili njegove soli, da se dobije spoj formule (IX):
[image]
i
2) reakciju spoja formule (IX) sa sredstvom za uklanjanje zaštite karboksilne kiseline, naznačen time što E1 je -OH, halid ili -C(=O)E1 je aktivirani ester; i P1 je zaštitna skupina karboksilne kiseline.
10. Postupak prema zahtjevu 9, naznačen time što je spoj formule (Xa) ili njegova sol predstavljen formulom (X-la):
[image]
ili njegova sol, koji obuhvaća korake:
1) reakciju spoja formule (VIII):
[image]
ili njegove soli, sa spojem formule (c-1):
[image]
ili njegove soli, da se dobije spoj formule (IX-1):
[image]
i
2) reakciju spoja formule (IX-1) sa sredstvom za uklanjanje zaštite karboksilne kiseline, naznačen time što E1 je -OH, halid ili -C(=O)E1 je aktivirani ester; i P1 je zaštitna skupina karboksilne kiseline.
11. Postupak za pripremu spoja formule (II),
[image]
koji obuhvaća reakciju spoja formule (I):
[image]
s klorovodičnom kiselinom u toluenu.
12. Postupak za pripremu spoja formule (IV-1):
[image]
ili njegova sol, koji obuhvaća korake:
1) reakciju spoja formule (I):
[image]
s klorovodičnom kiselinom u toluenu da se dobije spoj formule (II):
[image]
2) reakciju spoja formule (II) s monomernim spojem formule (a),
[image]
da se dobije spoj formule (III):
[image]
ili njegova sol;
3) reakciju spoja formule (III) ili njegove soli s monomernim spojem formule (b):
[image]
da nastane spoj formule (IV-1) ili njegova sol.
13. Postupak za pripremu spoja formule (A-1):
[image]
ili njegova sol, koji obuhvaća korake:
1) reakciju spoja formule (I):
[image]
s klorovodičnom kiselinom u toluenu da se dobije spoj formule (II):
[image]
2) reakciju spoja formule (II) s monomernim spojem formule (a),
[image]
da se dobije spoj formule (III):
[image]
ili njegova sol;
3) reakciju spoja formule (III) ili njegove soli s monomernim spojem formule (b):
[image]
da se dobije spoj formule (IV-1):
[image]
ili njegova sol;
4) reakciju spoja formule (IV-1) ili njegove soli s redukcijskim sredstvom da se dobije spoj formule (V-1):
[image]
ili njegova sol; i
5) reakciju spoja formule (V-1) ili njegove soli, sa spojem formule (X-1):
[image]
da nastane spoj formule (A-1) ili njegova sol, naznačen time što E je -OH, halid ili -C(=O)E je aktivirani ester.
14. Postupak prema zahtjevu 11, 12 ili 13, naznačen time što 30-38 w/w% klorovodične kiseline u vodi reagira sa spojem formule (I).
15. Postupak prema bilo kojem od zahtjeva 12-14, naznačen time što u koraku 2),
spoj formule (II) reagira s monomernim spojem formule (a) u prisutnosti sredstva za aktiviranje alkohola, izborno gdje je sredstvo za aktiviranje alkohola trialkilfosfin, triarilfosfin, ili triheteroarilfosfin, poželjno tributilfosfin; i
izborno pri čemu spoj formule (II) reagira s monomernim spojem formule (a) u prisutnosti azodikarboksilata, izborno pri čemu je azodikarboksilat odabran iz skupine koju čine: dietil azodikarboksilat (DEAD), diizopropil azodikarboksilat (DIAD), 1,1'- (azodikarbonil)dipiperidin (ADDP), i ditertbutil azodikarboksilat (DTAD).
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762450270P | 2017-01-25 | 2017-01-25 | |
| PCT/US2018/014956 WO2018140435A1 (en) | 2017-01-25 | 2018-01-24 | Methods of preparing cytotoxic benzodiazepine derivatives |
| EP18704352.6A EP3573948B1 (en) | 2017-01-25 | 2018-01-24 | Methods of preparing cytotoxic benzodiazepine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20230002T1 true HRP20230002T1 (hr) | 2023-02-17 |
Family
ID=61189535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20230002TT HRP20230002T1 (hr) | 2017-01-25 | 2018-01-24 | Postupci pripreme citotoksičnih derivata benzodiazepina |
Country Status (22)
| Country | Link |
|---|---|
| US (4) | US10385071B2 (hr) |
| EP (2) | EP4148044A1 (hr) |
| JP (3) | JP7066725B2 (hr) |
| KR (2) | KR102480594B1 (hr) |
| CN (3) | CN116554262A (hr) |
| AU (3) | AU2018213202B2 (hr) |
| CA (1) | CA3050262A1 (hr) |
| DK (1) | DK3573948T3 (hr) |
| ES (1) | ES2935346T3 (hr) |
| FI (1) | FI3573948T3 (hr) |
| HR (1) | HRP20230002T1 (hr) |
| HU (1) | HUE060746T2 (hr) |
| IL (3) | IL293645A (hr) |
| LT (1) | LT3573948T (hr) |
| PL (1) | PL3573948T3 (hr) |
| PT (1) | PT3573948T (hr) |
| RS (1) | RS63871B1 (hr) |
| RU (2) | RU2021138005A (hr) |
| SG (1) | SG11201906666QA (hr) |
| SI (1) | SI3573948T1 (hr) |
| TW (3) | TWI763771B (hr) |
| WO (1) | WO2018140435A1 (hr) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SG11201906666QA (en) | 2017-01-25 | 2019-08-27 | Immunogen Inc | Methods of preparing cytotoxic benzodiazepine derivatives |
| KR20210099010A (ko) * | 2018-11-12 | 2021-08-11 | 이뮤노젠 아이엔씨 | 세포독성 벤조디아제핀 유도체의 제조 방법 |
| MA54228A (fr) | 2018-11-12 | 2021-09-22 | Immunogen Inc | Procédés de préparation de dérivés de benzodiazépine cytotoxiques |
| TW202102506A (zh) * | 2019-03-29 | 2021-01-16 | 美商伊繆諾金公司 | 苯二氮平衍生物 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9018601D0 (en) | 1990-08-24 | 1990-10-10 | Fujisawa Pharmaceutical Co | Tricyclic compounds |
| NZ610939A (en) | 2010-12-21 | 2014-07-25 | Janssen Pharmaceutica Nv | Novel antifungal 5,6-dihydro-4h-pyrrolo[1,2-a][1,4]- benzodiazepines and 6h-pyrrolo[1,2-a][1,4]benzodiazepines substituted with bicyclic benzene derivatives |
| EP3666289A1 (en) * | 2011-02-15 | 2020-06-17 | ImmunoGen, Inc. | Cytotoxic benzodiazepine derivatives |
| CA2973354A1 (en) | 2015-01-14 | 2016-07-21 | Bristol-Myers Squibb Company | Benzodiazepine dimers, conjugates thereof, and methods of making and using |
| RU2739612C2 (ru) * | 2015-06-29 | 2020-12-28 | Иммуноджен, Инк. | Анти-cd123 антитела и их конъюгаты и производные |
| PL3325482T3 (pl) | 2015-07-21 | 2021-01-11 | Immunogen, Inc. | Sposoby otrzymywania cytotoksycznych pochodnych benzodiazepiny |
| SG11201906666QA (en) | 2017-01-25 | 2019-08-27 | Immunogen Inc | Methods of preparing cytotoxic benzodiazepine derivatives |
-
2018
- 2018-01-24 SG SG11201906666QA patent/SG11201906666QA/en unknown
- 2018-01-24 FI FIEP18704352.6T patent/FI3573948T3/fi active
- 2018-01-24 SI SI201830832T patent/SI3573948T1/sl unknown
- 2018-01-24 RS RS20221193A patent/RS63871B1/sr unknown
- 2018-01-24 DK DK18704352.6T patent/DK3573948T3/da active
- 2018-01-24 WO PCT/US2018/014956 patent/WO2018140435A1/en unknown
- 2018-01-24 CN CN202310124650.6A patent/CN116554262A/zh active Pending
- 2018-01-24 PT PT187043526T patent/PT3573948T/pt unknown
- 2018-01-24 JP JP2019540404A patent/JP7066725B2/ja active Active
- 2018-01-24 ES ES18704352T patent/ES2935346T3/es active Active
- 2018-01-24 TW TW107102506A patent/TWI763771B/zh active
- 2018-01-24 RU RU2021138005A patent/RU2021138005A/ru unknown
- 2018-01-24 TW TW112117953A patent/TW202400551A/zh unknown
- 2018-01-24 LT LTEPPCT/US2018/014956T patent/LT3573948T/lt unknown
- 2018-01-24 TW TW111114178A patent/TWI805325B/zh active
- 2018-01-24 KR KR1020197024738A patent/KR102480594B1/ko active IP Right Grant
- 2018-01-24 IL IL293645A patent/IL293645A/en unknown
- 2018-01-24 CN CN202310124604.6A patent/CN116102615A/zh active Pending
- 2018-01-24 US US15/878,991 patent/US10385071B2/en active Active
- 2018-01-24 IL IL287405A patent/IL287405B/en unknown
- 2018-01-24 KR KR1020227044421A patent/KR20230005410A/ko active IP Right Grant
- 2018-01-24 EP EP22199432.0A patent/EP4148044A1/en not_active Withdrawn
- 2018-01-24 AU AU2018213202A patent/AU2018213202B2/en active Active
- 2018-01-24 CN CN201880008141.4A patent/CN110225904B/zh active Active
- 2018-01-24 PL PL18704352.6T patent/PL3573948T3/pl unknown
- 2018-01-24 EP EP18704352.6A patent/EP3573948B1/en active Active
- 2018-01-24 HU HUE18704352A patent/HUE060746T2/hu unknown
- 2018-01-24 HR HRP20230002TT patent/HRP20230002T1/hr unknown
- 2018-01-24 RU RU2019125133A patent/RU2762891C2/ru active
- 2018-01-24 CA CA3050262A patent/CA3050262A1/en active Pending
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2019
- 2019-06-17 US US16/442,718 patent/US10844078B2/en active Active
- 2019-07-22 IL IL268213A patent/IL268213B/en unknown
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2020
- 2020-10-22 US US17/077,688 patent/US11390633B2/en active Active
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2022
- 2022-03-07 AU AU2022201572A patent/AU2022201572B2/en active Active
- 2022-04-27 JP JP2022072946A patent/JP7400005B2/ja active Active
- 2022-06-15 US US17/841,026 patent/US11981687B2/en active Active
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2023
- 2023-12-06 JP JP2023205788A patent/JP2024028860A/ja not_active Withdrawn
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2024
- 2024-02-21 AU AU2024201119A patent/AU2024201119A1/en active Pending
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