FR2461711A1 - Composes du 1h-pyrrolo-(2,1-c) (1,4) benzodiazepine-2-acrylamide, leur procede de preparation et compositions pharmaceutiques en contenant - Google Patents
Composes du 1h-pyrrolo-(2,1-c) (1,4) benzodiazepine-2-acrylamide, leur procede de preparation et compositions pharmaceutiques en contenant Download PDFInfo
- Publication number
- FR2461711A1 FR2461711A1 FR8006153A FR8006153A FR2461711A1 FR 2461711 A1 FR2461711 A1 FR 2461711A1 FR 8006153 A FR8006153 A FR 8006153A FR 8006153 A FR8006153 A FR 8006153A FR 2461711 A1 FR2461711 A1 FR 2461711A1
- Authority
- FR
- France
- Prior art keywords
- compound
- formula
- pyrrolo
- benzodiazepine
- acrylamide
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 title claims 2
- HGOZVUMJMGXJJB-UHFFFAOYSA-N 3-(7h-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)prop-2-enamide Chemical class C1=C2C=CC=CC2=NC=C2CC(C=CC(=O)N)=CN21 HGOZVUMJMGXJJB-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 52
- 239000001257 hydrogen Substances 0.000 claims abstract description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 12
- 150000001768 cations Chemical class 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 51
- 239000000203 mixture Substances 0.000 claims description 29
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 22
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 239000002184 metal Substances 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000002252 acyl group Chemical group 0.000 claims description 15
- BIVATAPISXAMKP-UHFFFAOYSA-N 3-(1h-1,4-benzodiazepin-2-yl)prop-2-enamide Chemical compound N1C(C=CC(=O)N)=CN=CC2=CC=CC=C21 BIVATAPISXAMKP-UHFFFAOYSA-N 0.000 claims description 14
- 229910052751 metal Inorganic materials 0.000 claims description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- 239000003513 alkali Substances 0.000 claims description 12
- -1 alkali metal cation Chemical class 0.000 claims description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 8
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 8
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- 238000006243 chemical reaction Methods 0.000 claims description 6
- 239000012442 inert solvent Substances 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 239000011593 sulfur Substances 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- RMGVZKRVHHSUIM-UHFFFAOYSA-N dithionic acid Chemical compound OS(=O)(=O)S(O)(=O)=O RMGVZKRVHHSUIM-UHFFFAOYSA-N 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- KRURGYOKPVLRHQ-UHFFFAOYSA-N trithionic acid Chemical compound OS(=O)(=O)SS(O)(=O)=O KRURGYOKPVLRHQ-UHFFFAOYSA-N 0.000 claims description 3
- 229910006127 SO3X Inorganic materials 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims 3
- 239000010931 gold Substances 0.000 claims 3
- 229910052737 gold Inorganic materials 0.000 claims 3
- 229910044991 metal oxide Inorganic materials 0.000 claims 2
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims 1
- 241001331845 Equus asinus x caballus Species 0.000 claims 1
- 229940049706 benzodiazepine Drugs 0.000 claims 1
- 229910001882 dioxygen Inorganic materials 0.000 claims 1
- GRWZHXKQBITJKP-UHFFFAOYSA-N dithionous acid Chemical compound OS(=O)S(O)=O GRWZHXKQBITJKP-UHFFFAOYSA-N 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 abstract description 2
- YZCKVEUIGOORGS-UHFFFAOYSA-N Hydrogen atom Chemical group [H] YZCKVEUIGOORGS-UHFFFAOYSA-N 0.000 abstract 1
- QGLZXHRNAYXIBU-UHFFFAOYSA-N aldicarb Chemical compound CNC(=O)ON=CC(C)(C)SC QGLZXHRNAYXIBU-UHFFFAOYSA-N 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 22
- 239000000243 solution Substances 0.000 description 17
- 239000013078 crystal Substances 0.000 description 13
- 238000000862 absorption spectrum Methods 0.000 description 12
- 230000008018 melting Effects 0.000 description 12
- 238000002844 melting Methods 0.000 description 12
- 230000000259 anti-tumor effect Effects 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 159000000000 sodium salts Chemical class 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- MRGGOAHOCOOIMN-UHFFFAOYSA-N 3-(9H-pyrrolo[2,1-c][1,4]benzodiazepin-8-yl)prop-2-enamide Chemical compound C1=C(CN2C1=CN=C1C(=C2)C=CC=C1)C=CC(=O)N MRGGOAHOCOOIMN-UHFFFAOYSA-N 0.000 description 3
- OBAIHJABYRUGAP-UHFFFAOYSA-N 3-(diazepin-1-yl)prop-2-enamide Chemical compound NC(=O)C=CN1C=CC=CC=N1 OBAIHJABYRUGAP-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- 229920001429 chelating resin Polymers 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 229910006069 SO3H Inorganic materials 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 2
- 229940075931 sodium dithionate Drugs 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
- PCJZRPDVONTWOJ-UHFFFAOYSA-N 3-(1,2-benzodiazepin-2-yl)prop-2-enamide Chemical compound NC(=O)C=CN1C=CC=C2C=CC=CC2=N1 PCJZRPDVONTWOJ-UHFFFAOYSA-N 0.000 description 1
- ZAYPYKHINXAARV-UHFFFAOYSA-N 7h-pyrrolo[2,1-c][1,4]benzodiazepine Chemical compound C1=C2C=CC=CC2=NC=C2CC=CN21 ZAYPYKHINXAARV-UHFFFAOYSA-N 0.000 description 1
- 101100005765 Arabidopsis thaliana CDF1 gene Proteins 0.000 description 1
- 101100007579 Arabidopsis thaliana CPP1 gene Proteins 0.000 description 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical group COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 229920006063 Lamide® Polymers 0.000 description 1
- 208000008342 Leukemia P388 Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- SPDXDEIWVPHXKJ-UHFFFAOYSA-N OC(C=CC1=CN=CC(C=CC=C2)=C2N1)=O Chemical class OC(C=CC1=CN=CC(C=CC=C2)=C2N1)=O SPDXDEIWVPHXKJ-UHFFFAOYSA-N 0.000 description 1
- 239000004285 Potassium sulphite Substances 0.000 description 1
- 229910006080 SO2X Inorganic materials 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- WVHBHPATSLQXGC-UHFFFAOYSA-N benzene;ethanol Chemical compound CCO.C1=CC=CC=C1 WVHBHPATSLQXGC-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 235000021590 normal diet Nutrition 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 description 1
- 235000019252 potassium sulphite Nutrition 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000000213 sulfino group Chemical group [H]OS(*)=O 0.000 description 1
- 150000003464 sulfur compounds Chemical class 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 238000002723 toxicity assay Methods 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
Classifications
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP8988679A JPS5615289A (en) | 1979-07-17 | 1979-07-17 | Novel benzodiazepinnbased compound 3 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| FR2461711A1 true FR2461711A1 (fr) | 1981-02-06 |
| FR2461711B1 FR2461711B1 (OSRAM) | 1983-05-13 |
Family
ID=13983232
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FR8006153A Granted FR2461711A1 (fr) | 1979-07-17 | 1980-03-19 | Composes du 1h-pyrrolo-(2,1-c) (1,4) benzodiazepine-2-acrylamide, leur procede de preparation et compositions pharmaceutiques en contenant |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4309437A (OSRAM) |
| JP (1) | JPS5615289A (OSRAM) |
| BE (1) | BE882305A (OSRAM) |
| CA (1) | CA1152985A (OSRAM) |
| CH (1) | CH648848A5 (OSRAM) |
| DE (1) | DE3010544C2 (OSRAM) |
| FR (1) | FR2461711A1 (OSRAM) |
| GB (1) | GB2053894B (OSRAM) |
| LU (1) | LU82272A1 (OSRAM) |
| NL (1) | NL8001531A (OSRAM) |
| SE (1) | SE436882B (OSRAM) |
Families Citing this family (62)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1214774A (en) * | 1983-02-10 | 1986-12-02 | Yusei Shiraga | Benzodiazepine derivative |
| JPS59152329A (ja) * | 1983-02-17 | 1984-08-31 | Green Cross Corp:The | 局所障害抑制剤 |
| JPS60168512U (ja) * | 1985-03-25 | 1985-11-08 | 株式会社栗田機械製作所 | 圧搾濾板の圧搾膜検査装置 |
| GB9818732D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
| GB9818731D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
| ES2260570T3 (es) * | 1998-08-27 | 2006-11-01 | Spirogen Limited | Pirrolobenziodiazepinas dimericas. |
| GB9818730D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
| US6909006B1 (en) | 1999-08-27 | 2005-06-21 | Spirogen Limited | Cyclopropylindole derivatives |
| GB0226593D0 (en) * | 2002-11-14 | 2002-12-24 | Consultants Ltd | Compounds |
| GB0321295D0 (en) * | 2003-09-11 | 2003-10-15 | Spirogen Ltd | Synthesis of protected pyrrolobenzodiazepines |
| PT2270010E (pt) * | 2004-03-01 | 2012-03-12 | Spirogen Ltd | Derivados de 11-hidroxi-5h-pirrolo[2,1-c][1,4]benzodiazepin- 5-ona como intermediários chave para a preparação de pirrolobenzodiazepinas substituídas em c2 |
| GB0404577D0 (en) * | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0404578D0 (en) * | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| US7528126B2 (en) * | 2004-03-09 | 2009-05-05 | Spirogen Limited | Pyrrolobenzodiazepines |
| BRPI0610284A8 (pt) * | 2005-04-21 | 2017-05-09 | Spirogen Ltd | Pirrolobenzodiazepinas |
| GB0813432D0 (en) * | 2008-07-22 | 2008-08-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0819095D0 (en) | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| ES2623057T3 (es) | 2010-04-15 | 2017-07-10 | Medimmune Limited | Pirrolobenzodiazepinas usadas para tratar enfermedades proliferativas |
| GB201006340D0 (en) | 2010-04-15 | 2010-06-02 | Spirogen Ltd | Synthesis method and intermediates |
| CN107019804A (zh) | 2010-04-15 | 2017-08-08 | 西雅图基因公司 | 靶向吡咯并苯并二氮杂卓结合物 |
| MX341524B (es) | 2011-09-20 | 2016-08-24 | Medimmune Ltd | Pirrolobenzodiazepinas como compuestos pbd dimericos asimetricos para inclusion en conjugados dirigidos. |
| EA027386B1 (ru) | 2011-10-14 | 2017-07-31 | Медимьюн Лимитед | Пирролобензодиазепины |
| MX341523B (es) | 2011-10-14 | 2016-08-24 | Medimmune Ltd | Pirrolobenzodiazepinas. |
| AU2012322933B2 (en) | 2011-10-14 | 2017-02-02 | Medimmune Limited | Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines |
| ES2660233T3 (es) | 2011-10-14 | 2018-03-21 | Seattle Genetics, Inc. | Pirrolobenzodiazepinas y conjugados dirigidos |
| CA2850373C (en) | 2011-10-14 | 2019-07-16 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| JP6125614B2 (ja) | 2012-04-30 | 2017-05-10 | ユーシーエル ビジネス ピーエルシー | ピロロベンゾジアゼピン |
| SI2906251T1 (en) | 2012-10-12 | 2018-01-31 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-anti-cd22 antibody conjugates |
| SMT201900017T1 (it) | 2012-10-12 | 2019-02-28 | Medimmune Ltd | Coniugati pirrolobenzodiazepina-anticorpo |
| WO2014057072A1 (en) | 2012-10-12 | 2014-04-17 | Spirogen Sàrl | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
| DK2906296T3 (en) | 2012-10-12 | 2018-05-22 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
| CA2941485C (en) | 2012-10-12 | 2018-06-12 | Philip Wilson Howard | Pyrrolobenzodiazepines and conjugates thereof |
| US10695433B2 (en) | 2012-10-12 | 2020-06-30 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| CN110256469B (zh) | 2012-10-12 | 2022-05-17 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂卓及其结合物 |
| US10736903B2 (en) | 2012-10-12 | 2020-08-11 | Medimmune Limited | Pyrrolobenzodiazepine-anti-PSMA antibody conjugates |
| PL2906253T3 (pl) | 2012-10-12 | 2019-02-28 | Adc Therapeutics Sa | Koniugaty pirolobenzodiazepina-przeciwciało anty-psma |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| US9956299B2 (en) | 2013-10-11 | 2018-05-01 | Medimmune Limited | Pyrrolobenzodiazepine—antibody conjugates |
| GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
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| WO2017201132A2 (en) | 2016-05-18 | 2017-11-23 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepines and conjugates thereof |
| TWI760344B (zh) | 2016-06-24 | 2022-04-11 | 美商梅爾莎納醫療公司 | 吡咯並苯並二氮呯類和彼等之共軛物類 |
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| SMT202100543T1 (it) | 2017-02-08 | 2021-11-12 | Adc Therapeutics Sa | Coniugati pirrolobenzodiazepina-anticorpo |
| GB201702031D0 (en) | 2017-02-08 | 2017-03-22 | Medlmmune Ltd | Pyrrolobenzodiazepine-antibody conjugates |
| SMT202200490T1 (it) | 2017-04-18 | 2023-01-13 | Medimmune Ltd | Coniugati di pirrolobenzodiazepina |
| US20200129637A1 (en) | 2017-04-20 | 2020-04-30 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
| EP3638373B1 (en) | 2017-06-14 | 2024-09-04 | ADC Therapeutics SA | Dosage regimes for the administration of an anti-cd19 adc |
| CN111065638B (zh) | 2017-08-18 | 2021-04-09 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂䓬缀合物 |
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| US12209099B2 (en) | 2019-03-15 | 2025-01-28 | Medimmune Limited | Azetidobenzodiazepine dimers and conjugates comprising them for use in the treatment of cancer |
| USD925487S1 (en) * | 2019-10-22 | 2021-07-20 | Lg Electronics Inc. | Audio player |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3523941A (en) * | 1967-03-06 | 1970-08-11 | Hoffmann La Roche | Benzodiazepine compounds and process for their preparation |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3524849A (en) * | 1967-10-27 | 1970-08-18 | Hoffmann La Roche | Process for the preparation of pyrrolo-benzodiazepine acrylamides and intermediates useful therein |
-
1979
- 1979-07-17 JP JP8988679A patent/JPS5615289A/ja active Granted
-
1980
- 1980-02-25 SE SE8001458A patent/SE436882B/sv not_active IP Right Cessation
- 1980-02-27 CA CA000346511A patent/CA1152985A/en not_active Expired
- 1980-03-04 US US06/127,984 patent/US4309437A/en not_active Expired - Lifetime
- 1980-03-10 GB GB8008033A patent/GB2053894B/en not_active Expired
- 1980-03-14 NL NL8001531A patent/NL8001531A/nl not_active Application Discontinuation
- 1980-03-19 FR FR8006153A patent/FR2461711A1/fr active Granted
- 1980-03-19 LU LU82272A patent/LU82272A1/fr unknown
- 1980-03-19 DE DE3010544A patent/DE3010544C2/de not_active Expired
- 1980-03-19 BE BE0/199851A patent/BE882305A/fr not_active IP Right Cessation
- 1980-03-20 CH CH2187/80A patent/CH648848A5/de not_active IP Right Cessation
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3523941A (en) * | 1967-03-06 | 1970-08-11 | Hoffmann La Roche | Benzodiazepine compounds and process for their preparation |
Also Published As
| Publication number | Publication date |
|---|---|
| NL8001531A (nl) | 1981-01-20 |
| GB2053894A (en) | 1981-02-11 |
| SE436882B (sv) | 1985-01-28 |
| DE3010544C2 (de) | 1982-07-01 |
| LU82272A1 (fr) | 1980-07-01 |
| JPS6237631B2 (OSRAM) | 1987-08-13 |
| DE3010544A1 (de) | 1981-01-29 |
| BE882305A (fr) | 1980-07-16 |
| GB2053894B (en) | 1983-04-20 |
| FR2461711B1 (OSRAM) | 1983-05-13 |
| SE8001458L (sv) | 1981-01-18 |
| US4309437A (en) | 1982-01-05 |
| CH648848A5 (de) | 1985-04-15 |
| CA1152985A (en) | 1983-08-30 |
| JPS5615289A (en) | 1981-02-14 |
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