ES2205872T3 - Pirrolobenzodiaepinas. - Google Patents
Pirrolobenzodiaepinas.Info
- Publication number
- ES2205872T3 ES2205872T3 ES99941766T ES99941766T ES2205872T3 ES 2205872 T3 ES2205872 T3 ES 2205872T3 ES 99941766 T ES99941766 T ES 99941766T ES 99941766 T ES99941766 T ES 99941766T ES 2205872 T3 ES2205872 T3 ES 2205872T3
- Authority
- ES
- Spain
- Prior art keywords
- compound
- formula
- carbon
- group
- use according
- 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.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 130
- 238000000034 method Methods 0.000 claims abstract description 53
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 25
- 238000010914 gene-directed enzyme pro-drug therapy Methods 0.000 claims abstract description 16
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000010913 antigen-directed enzyme pro-drug therapy Methods 0.000 claims abstract 2
- 102000004190 Enzymes Human genes 0.000 claims description 56
- 108090000790 Enzymes Proteins 0.000 claims description 56
- -1 hydroxy, amino Chemical group 0.000 claims description 35
- 239000000539 dimer Substances 0.000 claims description 25
- 239000003814 drug Substances 0.000 claims description 24
- 238000011282 treatment Methods 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 125000004429 atom Chemical group 0.000 claims description 20
- 229940079593 drug Drugs 0.000 claims description 19
- 239000000178 monomer Substances 0.000 claims description 15
- 102000004459 Nitroreductase Human genes 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 108020001162 nitroreductase Proteins 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 8
- 102000005720 Glutathione transferase Human genes 0.000 claims description 7
- 108010070675 Glutathione transferase Proteins 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000001613 neoplastic effect Effects 0.000 claims description 5
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 238000005304 joining Methods 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 6
- 230000001681 protective effect Effects 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 150
- 239000000243 solution Substances 0.000 description 98
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 76
- 230000015572 biosynthetic process Effects 0.000 description 71
- 210000004027 cell Anatomy 0.000 description 69
- 238000003786 synthesis reaction Methods 0.000 description 69
- 229940002612 prodrug Drugs 0.000 description 64
- 239000000651 prodrug Substances 0.000 description 64
- 239000011541 reaction mixture Substances 0.000 description 49
- 238000003756 stirring Methods 0.000 description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 239000003921 oil Substances 0.000 description 43
- 235000019198 oils Nutrition 0.000 description 43
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- 238000006243 chemical reaction Methods 0.000 description 34
- 239000000203 mixture Substances 0.000 description 34
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 33
- 238000005160 1H NMR spectroscopy Methods 0.000 description 33
- 239000012299 nitrogen atmosphere Substances 0.000 description 33
- 239000000047 product Substances 0.000 description 32
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 31
- 150000001412 amines Chemical class 0.000 description 28
- 239000012267 brine Substances 0.000 description 26
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 26
- 206010028980 Neoplasm Diseases 0.000 description 25
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 239000013598 vector Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000003818 flash chromatography Methods 0.000 description 24
- 239000002253 acid Substances 0.000 description 22
- 238000004809 thin layer chromatography Methods 0.000 description 22
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
- 230000004913 activation Effects 0.000 description 18
- 238000001994 activation Methods 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- PWDSJBHSKYBUEX-UHFFFAOYSA-N 1,4-benzodiazepin-5-one Chemical compound O=C1N=CC=NC2=CC=CC=C12 PWDSJBHSKYBUEX-UHFFFAOYSA-N 0.000 description 16
- 241000790917 Dioxys <bee> Species 0.000 description 16
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 16
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000003208 petroleum Substances 0.000 description 15
- GUFUWKKDHIABBW-UHFFFAOYSA-N pyrrolidin-1-ylmethanol Chemical compound OCN1CCCC1 GUFUWKKDHIABBW-UHFFFAOYSA-N 0.000 description 15
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 14
- LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 14
- 238000001914 filtration Methods 0.000 description 14
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 14
- 238000002428 photodynamic therapy Methods 0.000 description 14
- 238000002560 therapeutic procedure Methods 0.000 description 14
- 210000004881 tumor cell Anatomy 0.000 description 14
- 230000003013 cytotoxicity Effects 0.000 description 13
- 231100000135 cytotoxicity Toxicity 0.000 description 13
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 12
- 150000001299 aldehydes Chemical class 0.000 description 12
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 12
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
- VTHHRADLOLKTLD-UHFFFAOYSA-N 4-(benzyloxy)-5-methoxy-2-nitrobenzoic acid Chemical compound COC1=CC(C(O)=O)=C([N+]([O-])=O)C=C1OCC1=CC=CC=C1 VTHHRADLOLKTLD-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000003242 anti bacterial agent Substances 0.000 description 11
- 229940088710 antibiotic agent Drugs 0.000 description 11
- NNWJWOBAKPTVJQ-DEQUOLNYSA-N (6as)-6-hydroxy-2-methoxy-5-[(4-nitrophenyl)methoxy]-11-oxo-3-phenylmethoxy-6a,7,8,9-tetrahydro-6h-pyrrolo[2,1-c][1,4]benzodiazepine-7-carboxylic acid Chemical compound COC1=CC(C(N2CCC([C@H]2C(O)N2OCC=3C=CC(=CC=3)[N+]([O-])=O)C(O)=O)=O)=C2C=C1OCC1=CC=CC=C1 NNWJWOBAKPTVJQ-DEQUOLNYSA-N 0.000 description 10
- LSBDFXRDZJMBSC-UHFFFAOYSA-N 2-phenylacetamide Chemical compound NC(=O)CC1=CC=CC=C1 LSBDFXRDZJMBSC-UHFFFAOYSA-N 0.000 description 10
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 10
- 239000007924 injection Substances 0.000 description 10
- 238000002347 injection Methods 0.000 description 10
- 239000002502 liposome Substances 0.000 description 10
- 239000002808 molecular sieve Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- DWOHOXQIYBJNJS-UHFFFAOYSA-N 5-methoxy-2-nitro-4-propoxybenzoic acid Chemical compound CCCOC1=CC([N+]([O-])=O)=C(C(O)=O)C=C1OC DWOHOXQIYBJNJS-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 150000001241 acetals Chemical class 0.000 description 9
- 150000002828 nitro derivatives Chemical class 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 9
- 239000007787 solid Substances 0.000 description 9
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- 210000001519 tissue Anatomy 0.000 description 9
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- 230000003612 virological effect Effects 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
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- 150000002576 ketones Chemical class 0.000 description 8
- 230000003647 oxidation Effects 0.000 description 8
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- NQLRKKYEAIYVMB-HPZKVCJDSA-N (3ar)-7-[3-[[(6as)-11-oxo-6a,7,8,9-tetrahydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-8-methoxy-2,3,3a,10a-tetrahydro-1h-pyrrolo[3,2-c][1]benzazepin-10-one Chemical compound C1=C2N=C[C@@H]3CCCN3C(=O)C2=CC=C1OCCCOC1=CC(N=C[C@H]2C(NCC2)C2=O)=C2C=C1OC NQLRKKYEAIYVMB-HPZKVCJDSA-N 0.000 description 7
- BQXUPNKLZNSUMC-YUQWMIPFSA-N CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 Chemical compound CCN(CCCCCOCC(=O)N[C@H](C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@@H](C)c1ccc(cc1)-c1scnc1C)C(C)(C)C)CCOc1ccc(cc1)C(=O)c1c(sc2cc(O)ccc12)-c1ccc(O)cc1 BQXUPNKLZNSUMC-YUQWMIPFSA-N 0.000 description 7
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- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
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- 238000012360 testing method Methods 0.000 description 6
- HKXGXGVWIPRDEP-UHFFFAOYSA-N 1-(6-fluoro-1h-benzimidazol-2-yl)ethanone Chemical compound C1=C(F)C=C2NC(C(=O)C)=NC2=C1 HKXGXGVWIPRDEP-UHFFFAOYSA-N 0.000 description 5
- PYAZCFCEURLPSU-UHFFFAOYSA-N 3-methoxy-4-propoxybenzoic acid Chemical compound CCCOC1=CC=C(C(O)=O)C=C1OC PYAZCFCEURLPSU-UHFFFAOYSA-N 0.000 description 5
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- 230000009471 action Effects 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
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- 229910052736 halogen Inorganic materials 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
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- XMYQHJDBLRZMLW-UHFFFAOYSA-N methanolamine Chemical compound NCO XMYQHJDBLRZMLW-UHFFFAOYSA-N 0.000 description 5
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 5
- BOPGDPNILDQYTO-NNYOXOHSSA-N nicotinamide-adenine dinucleotide Chemical compound C1=CCC(C(=O)N)=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC=NC(N)=C3N=C2)O)O1 BOPGDPNILDQYTO-NNYOXOHSSA-N 0.000 description 5
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- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 4
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- YUYIORPWPCVEMZ-UHFFFAOYSA-N (5-methoxy-4-propoxycyclohexa-2,4-dien-1-ylidene)methanone Chemical compound CCCOC1=C(OC)CC(=C=O)C=C1 YUYIORPWPCVEMZ-UHFFFAOYSA-N 0.000 description 3
- WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 3
- IBOFVQJTBBUKMU-UHFFFAOYSA-N 4,4'-methylene-bis-(2-chloroaniline) Chemical compound C1=C(Cl)C(N)=CC=C1CC1=CC=C(N)C(Cl)=C1 IBOFVQJTBBUKMU-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- 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
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- 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
- A61P31/10—Antimycotics
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- A—HUMAN NECESSITIES
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- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Virology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9818731 | 1998-08-27 | ||
| GBGB9818731.3A GB9818731D0 (en) | 1998-08-27 | 1998-08-27 | Compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2205872T3 true ES2205872T3 (es) | 2004-05-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES99941766T Expired - Lifetime ES2205872T3 (es) | 1998-08-27 | 1999-08-27 | Pirrolobenzodiaepinas. |
Country Status (12)
| Country | Link |
|---|---|
| US (2) | US6562806B1 (enExample) |
| EP (1) | EP1109811B1 (enExample) |
| JP (1) | JP4669611B2 (enExample) |
| AT (1) | ATE246687T1 (enExample) |
| CA (1) | CA2341968C (enExample) |
| DE (1) | DE69910227T2 (enExample) |
| DK (1) | DK1109811T3 (enExample) |
| ES (1) | ES2205872T3 (enExample) |
| GB (1) | GB9818731D0 (enExample) |
| NZ (1) | NZ510492A (enExample) |
| PT (1) | PT1109811E (enExample) |
| WO (1) | WO2000012507A2 (enExample) |
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| GB9818732D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
| GB9818730D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
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| FR2844273B1 (fr) | 2002-09-05 | 2008-04-04 | Aventis Pharma Sa | Nouveaux composes heterocycliques, procede et intermediaires de preparation et utilisation comme medicament, notamment comme inhibiteurs de beta-lactamases et anti-bacteriens. |
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| 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 |
| US3524849A (en) | 1967-10-27 | 1970-08-18 | Hoffmann La Roche | Process for the preparation of pyrrolo-benzodiazepine acrylamides and intermediates useful therein |
| DE1965304A1 (de) | 1968-12-30 | 1970-07-23 | Fujisawa Pharmaceutical Co | Benzdiazepinon-Verbindungen und Verfahren zu ihrer Herstellung |
| JPS585916B2 (ja) * | 1977-12-27 | 1983-02-02 | 株式会社ミドリ十字 | 新規ベンゾジアゼピン系化合物 |
| JPS5615289A (en) * | 1979-07-17 | 1981-02-14 | Green Cross Corp:The | Novel benzodiazepinnbased compound 3 |
| JPS58180487A (ja) | 1982-04-16 | 1983-10-21 | Kyowa Hakko Kogyo Co Ltd | 抗生物質ｄｃ−８１およびその製造法 |
| FR2586683B1 (fr) | 1985-08-29 | 1988-07-01 | Centre Nat Rech Scient | Nouveaux derives de neothramycine, leur procede de preparation et leur application en tant que medicaments |
| GB8607679D0 (en) | 1986-03-27 | 1986-04-30 | Winter G P | Recombinant dna product |
| GB8705477D0 (en) | 1987-03-09 | 1987-04-15 | Carlton Med Prod | Drug delivery systems |
| GB8809616D0 (en) | 1988-04-22 | 1988-05-25 | Cancer Res Campaign Tech | Further improvements relating to drug delivery systems |
| US5143854A (en) * | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
| FR2676230B1 (fr) | 1991-05-07 | 1993-08-27 | Centre Nat Rech Scient | Nouveaux derives de pyrrolo [1,4]-benzodiazepines, leur procede de preparation et medicaments les contenant. |
| AU681337B2 (en) | 1991-10-23 | 1997-08-28 | Cancer Research Campaign Technology Limited | Bacterial nitroreductase for the reduction of CB 1954 and analogues thereof to a cytotoxic form |
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| GB9818732D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
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| GB9818731D0 (en) * | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
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-
1998
- 1998-08-27 GB GBGB9818731.3A patent/GB9818731D0/en not_active Ceased
-
1999
- 1999-08-27 NZ NZ510492A patent/NZ510492A/en not_active IP Right Cessation
- 1999-08-27 US US09/763,814 patent/US6562806B1/en not_active Expired - Lifetime
- 1999-08-27 PT PT99941766T patent/PT1109811E/pt unknown
- 1999-08-27 CA CA002341968A patent/CA2341968C/en not_active Expired - Lifetime
- 1999-08-27 EP EP99941766A patent/EP1109811B1/en not_active Expired - Lifetime
- 1999-08-27 DE DE69910227T patent/DE69910227T2/de not_active Expired - Lifetime
- 1999-08-27 DK DK99941766T patent/DK1109811T3/da active
- 1999-08-27 ES ES99941766T patent/ES2205872T3/es not_active Expired - Lifetime
- 1999-08-27 AT AT99941766T patent/ATE246687T1/de active
- 1999-08-27 WO PCT/GB1999/002837 patent/WO2000012507A2/en not_active Ceased
- 1999-08-27 JP JP2000571053A patent/JP4669611B2/ja not_active Expired - Lifetime
-
2003
- 2003-03-04 US US10/379,049 patent/US20030195196A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CA2341968C (en) | 2009-04-07 |
| CA2341968A1 (en) | 2000-03-09 |
| WO2000012507A3 (en) | 2000-08-31 |
| WO2000012507A8 (en) | 2000-10-19 |
| GB9818731D0 (en) | 1998-10-21 |
| EP1109811B1 (en) | 2003-08-06 |
| DE69910227T2 (de) | 2004-06-17 |
| DK1109811T3 (da) | 2003-11-24 |
| US20030195196A1 (en) | 2003-10-16 |
| JP4669611B2 (ja) | 2011-04-13 |
| JP2002525284A (ja) | 2002-08-13 |
| EP1109811A2 (en) | 2001-06-27 |
| ATE246687T1 (de) | 2003-08-15 |
| PT1109811E (pt) | 2003-12-31 |
| US6562806B1 (en) | 2003-05-13 |
| WO2000012507A2 (en) | 2000-03-09 |
| NZ510492A (en) | 2003-08-29 |
| DE69910227D1 (de) | 2003-09-11 |
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