CA2850103C - Pyrrolobenzodiazepines - Google Patents
Pyrrolobenzodiazepines Download PDFInfo
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- CA2850103C CA2850103C CA2850103A CA2850103A CA2850103C CA 2850103 C CA2850103 C CA 2850103C CA 2850103 A CA2850103 A CA 2850103A CA 2850103 A CA2850103 A CA 2850103A CA 2850103 C CA2850103 C CA 2850103C
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- YUOCYTRGANSSRY-UHFFFAOYSA-N pyrrolo[2,3-i][1,2]benzodiazepine Chemical class C1=CN=NC2=C3C=CN=C3C=CC2=C1 YUOCYTRGANSSRY-UHFFFAOYSA-N 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 126
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 104
- 125000003118 aryl group Chemical group 0.000 claims abstract description 87
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 55
- 125000001424 substituent group Chemical group 0.000 claims abstract description 54
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 43
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 37
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 34
- 125000005843 halogen group Chemical group 0.000 claims abstract description 30
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 19
- 150000001768 cations Chemical class 0.000 claims abstract description 14
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 14
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 12
- 229910052727 yttrium Inorganic materials 0.000 claims abstract description 12
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 7
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims abstract description 7
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- 125000000172 C5-C10 aryl group Chemical group 0.000 claims abstract description 3
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims abstract 2
- -1 methoxy, ethoxy Chemical group 0.000 claims description 97
- 239000003446 ligand Substances 0.000 claims description 95
- 239000003814 drug Substances 0.000 claims description 73
- 229940079593 drug Drugs 0.000 claims description 70
- 125000005647 linker group Chemical group 0.000 claims description 59
- 108010016626 Dipeptides Proteins 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 28
- 239000012453 solvate Substances 0.000 claims description 24
- OMRPLUKQNWNZAV-CONSDPRKSA-N (6as)-3-[3-[[(6as)-2-methoxy-8-(4-methoxyphenyl)-11-oxo-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-3-yl]oxy]propoxy]-8-(4-aminophenyl)-2-methoxy-6a,7-dihydropyrrolo[2,1-c][1,4]benzodiazepin-11-one Chemical compound C1=CC(OC)=CC=C1C1=CN2C(=O)C3=CC(OC)=C(OCCCOC=4C(=CC=5C(=O)N6C=C(C[C@H]6C=NC=5C=4)C=4C=CC(N)=CC=4)OC)C=C3N=C[C@@H]2C1 OMRPLUKQNWNZAV-CONSDPRKSA-N 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 230000002062 proliferating effect Effects 0.000 claims description 13
- 125000006850 spacer group Chemical group 0.000 claims description 12
- 125000003275 alpha amino acid group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 238000011282 treatment Methods 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 208000023275 Autoimmune disease Diseases 0.000 claims description 7
- GDIHDSKOVXEJQQ-UHFFFAOYSA-N NC(O)=O.NC(O)=O.NC(O)=O.N Chemical group NC(O)=O.NC(O)=O.NC(O)=O.N GDIHDSKOVXEJQQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 239000004472 Lysine Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 229960002173 citrulline Drugs 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002374 hemiaminals Chemical group 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- 229910002091 carbon monoxide Inorganic materials 0.000 claims 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 1
- 241000124008 Mammalia Species 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 13
- IBAHLNWTOIHLKE-UHFFFAOYSA-N cyano cyanate Chemical compound N#COC#N IBAHLNWTOIHLKE-UHFFFAOYSA-N 0.000 abstract description 4
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 133
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 66
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 239000000243 solution Substances 0.000 description 46
- 210000004027 cell Anatomy 0.000 description 39
- 239000000562 conjugate Substances 0.000 description 39
- 238000006243 chemical reaction Methods 0.000 description 38
- 125000006239 protecting group Chemical group 0.000 description 37
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 34
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 33
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 33
- 235000019341 magnesium sulphate Nutrition 0.000 description 33
- 239000000203 mixture Substances 0.000 description 33
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 29
- 238000003786 synthesis reaction Methods 0.000 description 29
- 239000011230 binding agent Substances 0.000 description 27
- 239000000047 product Substances 0.000 description 27
- 238000003756 stirring Methods 0.000 description 27
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- 235000001014 amino acid Nutrition 0.000 description 24
- 239000007787 solid Substances 0.000 description 24
- 150000001413 amino acids Chemical class 0.000 description 23
- 125000003277 amino group Chemical group 0.000 description 23
- 230000015572 biosynthetic process Effects 0.000 description 22
- 125000000524 functional group Chemical group 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000012267 brine Substances 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 21
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
- 125000006413 ring segment Chemical group 0.000 description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 238000000034 method Methods 0.000 description 17
- 108090000765 processed proteins & peptides Proteins 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 16
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 238000000746 purification Methods 0.000 description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 125000003342 alkenyl group Chemical group 0.000 description 13
- 125000000304 alkynyl group Chemical group 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000003643 water by type Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 102000005600 Cathepsins Human genes 0.000 description 12
- 108010084457 Cathepsins Proteins 0.000 description 12
- 239000000427 antigen Substances 0.000 description 12
- 102000036639 antigens Human genes 0.000 description 12
- 108091007433 antigens Proteins 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 230000009471 action Effects 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 239000012299 nitrogen atmosphere Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- VVJKKWFAADXIJK-UHFFFAOYSA-N Allylamine Chemical compound NCC=C VVJKKWFAADXIJK-UHFFFAOYSA-N 0.000 description 10
- 206010028980 Neoplasm Diseases 0.000 description 10
- 239000003242 anti bacterial agent Substances 0.000 description 10
- 229940088710 antibiotic agent Drugs 0.000 description 10
- 230000008878 coupling Effects 0.000 description 10
- 238000010168 coupling process Methods 0.000 description 10
- 238000005859 coupling reaction Methods 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 description 10
- 229920006395 saturated elastomer Polymers 0.000 description 10
- 238000004809 thin layer chromatography Methods 0.000 description 10
- 125000003396 thiol group Chemical group [H]S* 0.000 description 10
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 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 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 238000004949 mass spectrometry Methods 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 9
- ORLCYMQZIPSODD-UHFFFAOYSA-N 1-chloro-2-[chloro(2,2,2-trichloroethoxy)phosphoryl]oxybenzene Chemical compound ClC1=CC=CC=C1OP(Cl)(=O)OCC(Cl)(Cl)Cl ORLCYMQZIPSODD-UHFFFAOYSA-N 0.000 description 8
- LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 description 8
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
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- YMXFJTUQQVLJEN-UHFFFAOYSA-N pyrimidine Chemical compound C1=CN=CN=C1.C1=CN=CN=C1 YMXFJTUQQVLJEN-UHFFFAOYSA-N 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- ZZOKVYOCRSMTSS-UHFFFAOYSA-N 9h-fluoren-9-ylmethyl carbamate Chemical compound C1=CC=C2C(COC(=O)N)C3=CC=CC=C3C2=C1 ZZOKVYOCRSMTSS-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
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- 230000021615 conjugation Effects 0.000 description 7
- QWHNJUXXYKPLQM-UHFFFAOYSA-N dimethyl cyclopentane Natural products CC1(C)CCCC1 QWHNJUXXYKPLQM-UHFFFAOYSA-N 0.000 description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 7
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- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical compound C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
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- 238000004128 high performance liquid chromatography Methods 0.000 description 6
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Classifications
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/62—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being a protein, peptide or polyamino acid
- A61K47/65—Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/54—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic compound
- A61K47/549—Sugars, nucleosides, nucleotides or nucleic acids
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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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Biotechnology (AREA)
- Genetics & Genomics (AREA)
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- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Transplantation (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161547198P | 2011-10-14 | 2011-10-14 | |
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Families Citing this family (127)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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 |
| KR101772354B1 (ko) | 2010-04-15 | 2017-08-28 | 시애틀 지네틱스, 인크. | 표적화된 피롤로벤조디아제핀 접합체 |
| WO2013041606A1 (en) | 2011-09-20 | 2013-03-28 | Spirogen Sàrl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
| US9526798B2 (en) | 2011-10-14 | 2016-12-27 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| US9388187B2 (en) | 2011-10-14 | 2016-07-12 | Medimmune Limited | Pyrrolobenzodiazepines |
| BR112014008888A2 (pt) | 2011-10-14 | 2017-04-18 | Seattle Genetics Inc | pirrolobenzodiazepinas |
| MX358757B (es) | 2011-10-14 | 2018-09-03 | Seattle Genetics Inc | Pirrolobenzodiazepinas y conjugados dirigidos. |
| ES2680153T3 (es) | 2012-10-12 | 2018-09-04 | Adc Therapeutics Sa | Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas |
| HRP20190366T1 (hr) | 2012-10-12 | 2019-04-19 | Medimmune Limited | Pirolobenzodiazepini i njihovi konjugati |
| PL2906251T3 (pl) | 2012-10-12 | 2018-02-28 | Adc Therapeutics Sa | Koniugaty pirolobenzodiazepina-przeciwciało anty-CD22 |
| WO2014057117A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| MX364328B (es) | 2012-10-12 | 2019-04-23 | Medimmune Ltd | Conjugados del anticuerpo pirrolobenzodiazepina. |
| HRP20181646T2 (hr) | 2012-10-12 | 2019-08-09 | Adc Therapeutics Sa | Konjugati pirolobenzodiazepin - anti-psma protutijela |
| KR101645905B1 (ko) | 2012-10-12 | 2016-08-04 | 스피로즌 살 | 피롤로벤조디아제핀 및 그의 컨주게이트 |
| AU2013328673B2 (en) | 2012-10-12 | 2017-07-13 | Medimmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
| WO2014057120A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| AU2013366493B2 (en) | 2012-12-21 | 2017-08-24 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| CN105246894A (zh) | 2012-12-21 | 2016-01-13 | 斯皮罗根有限公司 | 用于治疗增殖性和自身免疫疾病的非对称吡咯并苯并二氮杂卓二聚物 |
| MX385713B (es) | 2013-03-13 | 2025-03-18 | Seagen Inc | Ciclodextrina y formulaciones de conjugados anticuerpo-fármaco. |
| JP6445519B2 (ja) | 2013-03-13 | 2018-12-26 | メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ | ピロロベンゾジアゼピン及びそのコンジュゲート |
| WO2014140862A2 (en) | 2013-03-13 | 2014-09-18 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| EP3441072B1 (en) | 2013-03-13 | 2020-12-30 | Seagen Inc. | Activated carbon filtration for purification of benzodiazepine adcs |
| AU2014233385C1 (en) | 2013-03-15 | 2019-09-19 | Regeneron Pharmaceuticals, Inc. | Biologically active molecules, conjugates thereof, and therapeutic uses |
| KR102252925B1 (ko) | 2013-08-26 | 2021-05-18 | 리제너론 파마슈티칼스 인코포레이티드 | 마크롤라이드 디아스테레오머를 포함하는 약제학적 조성물, 이의 합성 방법 및 치료학적 용도 |
| KR20160047567A (ko) * | 2013-08-28 | 2016-05-02 | 스템센트알엑스 인코포레이티드 | 조작된 항-dll3 접합체 및 사용 방법 |
| JP2016538318A (ja) | 2013-08-28 | 2016-12-08 | ステムセントリックス， インコーポレイテッド | 新規ｓｅｚ６モジュレーターおよび使用方法 |
| WO2015031698A1 (en) | 2013-08-28 | 2015-03-05 | Stem Centrx, Inc. | Site-specific antibody conjugation methods and compositions |
| US9950078B2 (en) | 2013-10-11 | 2018-04-24 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| US10010624B2 (en) | 2013-10-11 | 2018-07-03 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| EP3054986B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| CA3187392A1 (en) | 2013-10-15 | 2015-04-23 | Seagen Inc. | Pegylated drug-linkers for improved ligand-drug conjugate pharmacokinetics |
| CN103641834B (zh) * | 2013-12-12 | 2015-12-09 | 沈阳药科大学 | 吡咯并苯并二氮杂*类化合物及其制备方法和应用 |
| MX381017B (es) | 2013-12-16 | 2025-03-12 | Genentech Inc | Compuestos peptidomiméticos y conjugados anticuerpo-fármaco de estos. |
| TWI727919B (zh) | 2013-12-19 | 2021-05-21 | 美商西雅圖遺傳學公司 | 與標的-藥物結合物併用之亞甲基胺基甲酸酯連接物 |
| KR20170008202A (ko) | 2014-02-21 | 2017-01-23 | 애브비 스템센트알엑스 엘엘씨 | 흑색종에 사용하기 위한 항-ｄｌｌ3 항체 및 약물 접합체 |
| RS59077B1 (sr) | 2014-03-11 | 2019-09-30 | Regeneron Pharma | Anti-egfrviii antitela i njihova primena |
| WO2016037644A1 (en) | 2014-09-10 | 2016-03-17 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| AU2015314954B2 (en) | 2014-09-12 | 2021-05-13 | Genentech, Inc. | Anti-HER2 antibodies and immunoconjugates |
| GB201416112D0 (en) | 2014-09-12 | 2014-10-29 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| US10780096B2 (en) | 2014-11-25 | 2020-09-22 | Adc Therapeutics Sa | Pyrrolobenzodiazepine-antibody conjugates |
| WO2016115191A1 (en) | 2015-01-14 | 2016-07-21 | Bristol-Myers Squibb Company | Benzodiazepine dimers, conjugates thereof, and methods of making and using |
| ES2747386T3 (es) | 2015-01-14 | 2020-03-10 | Bristol Myers Squibb Co | Dímeros de benzodiacepina unidos por heteroarileno, conjugados de los mismos y métodos de preparación y uso |
| KR20240142591A (ko) | 2015-03-27 | 2024-09-30 | 리제너론 파아마슈티컬스, 인크. | 메이탄시노이드 유도체, 이의 컨주게이트, 및 사용 방법 |
| GB201506411D0 (en) | 2015-04-15 | 2015-05-27 | Bergenbio As | Humanized anti-axl antibodies |
| GB201506402D0 (en) | 2015-04-15 | 2015-05-27 | Berkel Patricius H C Van And Howard Philip W | Site-specific antibody-drug conjugates |
| EA201792516A1 (ru) | 2015-06-23 | 2018-05-31 | Бристол-Маерс Сквибб Компани | Макроциклические димеры бензодиазепина, их конъюгаты, получение и применение |
| US11191844B2 (en) | 2015-07-06 | 2021-12-07 | Regeneran Pharmaceuticals, Inc. | Multispecific antigen-binding molecules and uses thereof |
| NZ741261A (en) * | 2015-10-02 | 2019-11-29 | Genentech Inc | Pyrrolobenzodiazepine antibody drug conjugates and methods of use |
| US11229708B2 (en) | 2015-12-04 | 2022-01-25 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| US11793880B2 (en) | 2015-12-04 | 2023-10-24 | Seagen Inc. | Conjugates of quaternized tubulysin compounds |
| MA43416A (fr) | 2015-12-11 | 2018-10-17 | Regeneron Pharma | Méthodes pour ralentir ou empêcher la croissance de tumeurs résistantes au blocage de l'egfr et/ou d'erbb3 |
| KR102885186B1 (ko) | 2016-01-25 | 2025-11-17 | 리제너론 파아마슈티컬스, 인크. | 메이탄시노이드 유도체, 그의 접합체, 및 사용 방법 |
| GB201601431D0 (en) | 2016-01-26 | 2016-03-09 | Medimmune Ltd | Pyrrolobenzodiazepines |
| GB201602359D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| GB201602356D0 (en) | 2016-02-10 | 2016-03-23 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| MA43835A (fr) | 2016-03-25 | 2018-11-28 | Seattle Genetics Inc | Procédé de préparation de lieurs de médicaments pégylés et leurs intermédiaires |
| EP3448891A1 (en) | 2016-04-28 | 2019-03-06 | Regeneron Pharmaceuticals, Inc. | Methods of making multispecific antigen-binding molecules |
| GB201607478D0 (en) | 2016-04-29 | 2016-06-15 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| US10143695B2 (en) | 2016-05-18 | 2018-12-04 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepines and conjugates thereof |
| JP7049276B2 (ja) | 2016-06-24 | 2022-04-06 | メルサナ セラピューティクス インコーポレイテッド | ピロロベンゾジアゼピンおよびその結合体 |
| WO2018002902A1 (en) | 2016-07-01 | 2018-01-04 | Glaxosmithkline Intellectual Property (No.2) Limited | Antibody-drug conjugates and therapeutic methods using the same |
| WO2018058001A1 (en) | 2016-09-23 | 2018-03-29 | Regeneron Pharmaceuticals, Inc. | Anti-steap2 antibodies, antibody-drug conjugates, and bispecific antigen-binding molecules that bind steap2 and cd3, and uses thereof |
| HRP20221202T1 (hr) | 2016-09-23 | 2022-12-09 | Regeneron Pharmaceuticals, Inc. | Anti-muc16 (mucin 16) antitijela |
| GB201617466D0 (en) | 2016-10-14 | 2016-11-30 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
| KR20190074310A (ko) | 2016-11-08 | 2019-06-27 | 리제너론 파마슈티칼스 인코포레이티드 | 스테로이드 및 이의 단백질-접합체 |
| TWI782930B (zh) | 2016-11-16 | 2022-11-11 | 美商再生元醫藥公司 | 抗ｍｅｔ抗體，結合ｍｅｔ之雙特異性抗原結合分子及其使用方法 |
| UA125198C2 (uk) | 2017-02-08 | 2022-01-26 | Ейдісі Терапьютікс Са | Кон'югати піролобензодіазепін-антитіло |
| GB201702031D0 (en) | 2017-02-08 | 2017-03-22 | Medlmmune Ltd | Pyrrolobenzodiazepine-antibody conjugates |
| KR102648564B1 (ko) | 2017-03-24 | 2024-03-19 | 씨젠 인크. | 글루쿠로니드 약물-링커의 제조 공정 및 그 중간물 |
| SI3612537T1 (sl) | 2017-04-18 | 2022-10-28 | Medimmune Limited | Konjugati pirolobenzodiazepina |
| WO2018193102A1 (en) | 2017-04-20 | 2018-10-25 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
| CN111065622A (zh) | 2017-05-18 | 2020-04-24 | 里珍纳龙药品有限公司 | 双八氢菲羧酰胺类化合物及其蛋白质偶联物 |
| CA3063871A1 (en) | 2017-05-18 | 2018-11-22 | Regeneron Pharmaceuticals, Inc. | Cyclodextrin protein drug conjugates |
| EP3635009B1 (en) | 2017-06-07 | 2026-02-25 | Regeneron Pharmaceuticals, Inc. | Compositions and methods for internalizing enzymes |
| JP7145891B2 (ja) | 2017-06-14 | 2022-10-03 | アーデーセー セラピューティクス ソシエテ アノニム | 抗ｃｄ１９ ａｄｃを投与するための投与レジメ |
| BR112020003003A2 (pt) | 2017-08-18 | 2020-08-11 | Medimmune Limited | conjugados de pirrolobenzodiazepina |
| CN117003875A (zh) | 2017-09-29 | 2023-11-07 | 第一三共株式会社 | 抗体或其功能性片段、多核苷酸、表达载体、宿主细胞、糖链重构抗体、药物组合物、应用 |
| JP7426931B2 (ja) | 2017-11-07 | 2024-02-02 | レゲネロン ファーマシューティカルス，インコーポレーテッド | 抗体薬物コンジュゲートのための親水性リンカー |
| CN111417409B (zh) | 2017-11-14 | 2022-07-08 | 麦迪穆有限责任公司 | 吡咯并苯并二氮杂䓬缀合物 |
| US11638760B2 (en) | 2017-11-27 | 2023-05-02 | Mersana Therapeutics, Inc. | Pyrrolobenzodiazepine antibody conjugates |
| JP2021506883A (ja) | 2017-12-21 | 2021-02-22 | メルサナ セラピューティクス インコーポレイテッド | ピロロベンゾジアゼピン抗体結合体 |
| BR112020013492A2 (pt) | 2018-01-08 | 2020-12-08 | Regeneron Pharmaceuticals, Inc. | Esteroides e conjugados de anticorpo dos mesmos |
| GB201803342D0 (en) | 2018-03-01 | 2018-04-18 | Medimmune Ltd | Methods |
| MX2020010110A (es) | 2018-03-28 | 2020-11-06 | Mitsubishi Tanabe Pharma Corp | Conjugados de farmacos de agentes de union monoclonales de cmet, y usos de los mismos. |
| GB201806022D0 (en) | 2018-04-12 | 2018-05-30 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| IL278244B2 (en) | 2018-04-30 | 2026-01-01 | Regeneron Pharma | Antibodies and bispecific antigen-binding molecules that bind HER2 and/or APLP2, conjugates and uses thereof |
| KR20210008008A (ko) | 2018-05-09 | 2021-01-20 | 리제너론 파마슈티칼스 인코포레이티드 | 항-msr1 항체 및 이의 사용 방법 |
| MA52626A (fr) | 2018-05-17 | 2021-03-24 | Regeneron Pharma | Anticorps anti-cd63, conjugués et leurs utilisations |
| IL278973B2 (en) * | 2018-05-29 | 2025-07-01 | Intocell Inc | History of new benzodiazepines and their uses |
| CA3118026A1 (en) | 2018-10-31 | 2020-05-07 | Intocell, Inc. | Fused heterocyclic benzodiazepine derivatives and uses thereof |
| EP4428142A3 (en) | 2018-11-20 | 2024-11-20 | Regeneron Pharmaceuticals, Inc. | Bis-octahydrophenanthrene carboxamide derivatives and protein conjugates thereof |
| MY208067A (en) | 2018-12-21 | 2025-04-11 | Regeneron Pharma | Tubulysins and protein-tubulysin conjugates |
| WO2020132483A1 (en) | 2018-12-21 | 2020-06-25 | Regeneron Pharmaceuticals, Inc. | Rifamycin analogs and antibody-drug conjugates thereof |
| JP2022517767A (ja) | 2019-01-08 | 2022-03-10 | レゲネロン ファーマシューティカルス，インコーポレーテッド | 無痕跡型リンカー及びそのタンパク質－コンジュゲート |
| SG11202108525VA (en) | 2019-02-21 | 2021-09-29 | Regeneron Pharma | Methods of treating ocular cancer using anti-met antibodies and bispecific antigen binding molecules that bind met |
| MX2021010477A (es) | 2019-03-15 | 2021-10-01 | Medimmune Ltd | Dimeros de azetidobenzodiazepina y conjugados que los comprenden para uso en el tratamiento de cancer. |
| CN110078749B (zh) * | 2019-06-04 | 2021-01-01 | 贵州省中国科学院天然产物化学重点实验室(贵州医科大学天然产物化学重点实验室) | 3a，3a′-双呋喃[2,3-b]吲哚啉类化合物、制备方法、药物组合物及应用 |
| CN114340684B (zh) | 2019-09-16 | 2025-09-12 | 瑞泽恩制药公司 | 用于免疫pet成像的放射性标记的met结合蛋白 |
| US11814428B2 (en) | 2019-09-19 | 2023-11-14 | Regeneron Pharmaceuticals, Inc. | Anti-PTCRA antibody-drug conjugates and uses thereof |
| US20240123081A1 (en) | 2019-10-25 | 2024-04-18 | Medimmune, Llc | Branched moiety for use in conjugates |
| CN115210247A (zh) | 2019-12-31 | 2022-10-18 | 乐高化学生物科学股份有限公司 | 吡咯并苯二氮卓类衍生物及其配体-接头偶联物 |
| IL294989A (en) | 2020-01-24 | 2022-09-01 | Regeneron Pharma | Conjugated protein-antiviral compounds |
| MX2022010599A (es) | 2020-02-28 | 2022-09-09 | Regeneron Pharma | Moleculas biespecificas de union al antigeno que se unen a her2, y metodos de uso de los mismos. |
| US11701427B2 (en) | 2020-04-16 | 2023-07-18 | Regeneron Pharmaceuticals, Inc. | Diels-alder conjugation methods |
| CN115867563B (zh) | 2020-06-24 | 2025-06-27 | 里珍纳龙药品有限公司 | 微管溶素及蛋白质-微管溶素偶联物 |
| KR20240038138A (ko) | 2020-07-13 | 2024-03-22 | 리제너론 파마슈티칼스 인코포레이티드 | 단백질에서 글루타민 잔기에 접합된 캄토테신 유사체 및 그의 용도 |
| WO2022056494A1 (en) | 2020-09-14 | 2022-03-17 | Regeneron Pharmaceuticals, Inc. | Antibody-drug conjugates comprising glp1 peptidomimetics and uses thereof |
| NZ797493A (en) | 2020-10-22 | 2024-05-31 | Regeneron Pharma | Anti-fgfr2 antibodies and methods of use thereof |
| CA3220081A1 (en) | 2021-07-28 | 2023-02-02 | Thomas Nittoli | Protein-antiviral compound conjugates |
| US20230414775A1 (en) | 2021-12-29 | 2023-12-28 | Regeneron Pharmaceuticals, Inc. | Tubulysins and protein-tubulysin conjugates |
| MX2024008640A (es) | 2022-01-12 | 2024-07-24 | Regeneron Pharma | Analogos de camptotecina conjugados a un residuo de glutamina en una proteina y su uso. |
| AU2023208050A1 (en) | 2022-01-14 | 2024-07-04 | Regeneron Pharmaceuticals, Inc. | Verrucarin a derivatives and antibody drug conjugates thereof |
| EP4489855A1 (en) | 2022-03-11 | 2025-01-15 | Regeneron Pharmaceuticals, Inc. | Anti-glp1r antibody-drug conjugates comprising glp1 peptidomimetics and uses thereof |
| US20250367307A1 (en) | 2022-06-30 | 2025-12-04 | Toray Industries, Inc. | Pharmaceutical composition for cancer treatment and/or prevention |
| CN120239705A (zh) | 2022-07-21 | 2025-07-01 | 萤火虫生物股份有限公司 | 糖皮质激素受体激动剂和其缀合物 |
| EP4626553A2 (en) | 2022-11-30 | 2025-10-08 | Regeneron Pharmaceuticals, Inc. | Tlr7 agonists and antibody-drug-conjugates thereof |
| WO2024138000A1 (en) | 2022-12-21 | 2024-06-27 | Regeneron Pharmaceuticals, Inc. | Prodrugs of topoisomerase i inhibitor for adc conjugations and methods of use thereof |
| EP4661914A1 (en) | 2023-02-09 | 2025-12-17 | Regeneron Pharmaceuticals, Inc. | Antibody-drug conjugates via inverse electron demand diels-alder reactions |
| CN121240890A (zh) | 2023-04-18 | 2025-12-30 | 阿斯利康(瑞典)有限公司 | 包含可裂解接头的缀合物 |
| AU2024265507A1 (en) | 2023-05-02 | 2025-10-30 | Regeneron Pharmaceuticals, Inc. | Anti-human m-cadherin (cdh15) antibodies, conjugates, and uses thereof for delivery of genetic payloads to muscle cells |
| CN121568720A (zh) | 2023-07-10 | 2026-02-24 | 瑞泽恩制药公司 | 抗人类cacng1抗体-药物缀合物及其用途 |
| US20250171516A1 (en) | 2023-11-03 | 2025-05-29 | Regeneron Pharmaceuticals, Inc. | Peptide acids as a glp1r agonist and antibody-drug conjugates thereof |
| WO2025117727A1 (en) | 2023-11-29 | 2025-06-05 | Regeneron Pharmaceuticals, Inc. | Analogs of quinoxaline/quinoline cytotoxins, linker- payloads, protein-drug conjugates, and uses thereof |
| WO2026020031A2 (en) | 2024-07-18 | 2026-01-22 | Novarock Biotherapeutics, Ltd. | Cdh17 antibodies and uses thereof |
Family Cites Families (119)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3361742A (en) | 1964-12-07 | 1968-01-02 | Hoffmann La Roche | 5-oxo-1h-pyrrolo-[2, 1-c][1, 4]-benzodiazepin-2-crylamides |
| 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 |
| IL33558A (en) | 1968-12-30 | 1973-10-25 | Fujisawa Pharmaceutical Co | Antibiotic pyrrolo-benzodiazepine compound,its derivatives and processes for their production |
| JPS4843755B1 (enExample) | 1969-06-26 | 1973-12-20 | ||
| DE1965304A1 (de) | 1968-12-30 | 1970-07-23 | Fujisawa Pharmaceutical Co | Benzdiazepinon-Verbindungen und Verfahren zu ihrer Herstellung |
| JPS5382792U (enExample) | 1976-12-10 | 1978-07-08 | ||
| 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 |
| JPH0353356Y2 (enExample) | 1981-02-06 | 1991-11-21 | ||
| CA1185602A (en) | 1981-02-27 | 1985-04-16 | Emilio Kyburz | Imidazodiazepines |
| CA1184175A (en) | 1981-02-27 | 1985-03-19 | Walter Hunkeler | Imidazodiazepines |
| CA1173441A (en) | 1981-02-27 | 1984-08-28 | Hoffmann-La Roche Limited | Imidazodiazepines |
| 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 |
| JPS58180487U (ja) | 1982-05-28 | 1983-12-02 | 松下電工株式会社 | 光線式報知器の組立体 |
| US4427588A (en) | 1982-11-08 | 1984-01-24 | Bristol-Myers Company | Process for conversion of oxotomaymycin to tomaymycin |
| US4427587A (en) | 1982-11-10 | 1984-01-24 | Bristol-Myers Company | Total synthesis of antitumor antibiotics BBM-2040A and BBM-2040B |
| JPS59152329A (ja) | 1983-02-17 | 1984-08-31 | Green Cross Corp:The | 局所障害抑制剤 |
| JPS59190992A (ja) * | 1983-04-12 | 1984-10-29 | Green Cross Corp:The | ベンゾジアゼピン誘導体 |
| 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 |
| JP2660201B2 (ja) | 1988-08-05 | 1997-10-08 | 塩野義製薬株式会社 | 新規ピロロ［１，４］ベンゾジアゼピン誘導体および老人性痴呆薬 |
| 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. |
| GB9205051D0 (en) | 1992-03-09 | 1992-04-22 | Cancer Res Campaign Tech | Pyrrolobenzodiazepine derivatives,their preparation,and compositions containing them |
| FR2696176B1 (fr) | 1992-09-28 | 1994-11-10 | Synthelabo | Dérivés de pipéridine, leur préparation et leur application en thérapeutique. |
| US6214345B1 (en) | 1993-05-14 | 2001-04-10 | Bristol-Myers Squibb Co. | Lysosomal enzyme-cleavable antitumor drug conjugates |
| GB9316162D0 (en) | 1993-08-04 | 1993-09-22 | Zeneca Ltd | Fungicides |
| EP1754995B1 (en) | 1998-07-08 | 2012-04-04 | E Ink Corporation | Methods for achieving improved color in microencapsulted electrophoretic devices |
| GB9818730D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
| CA2341471C (en) | 1998-08-27 | 2009-04-07 | Spirogen Limited | Pyrrolbenzodiazepines |
| GB9818731D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
| GB9818732D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
| US6909006B1 (en) | 1999-08-27 | 2005-06-21 | Spirogen Limited | Cyclopropylindole derivatives |
| CN1315805C (zh) | 2000-09-19 | 2007-05-16 | 斯皮罗根公司 | Cc－1065和多卡米新的非手性类似物的组合物及其使用方法 |
| US6362331B1 (en) | 2001-03-30 | 2002-03-26 | Council Of Scientific And Industrial Research | Process for the preparation of antitumor agents |
| US6660856B2 (en) | 2002-03-08 | 2003-12-09 | Kaohsiung Medical University | Synthesis of pyrrolo[2,1-c][1,4]benzodiazepine analogues |
| DK1545613T3 (da) | 2002-07-31 | 2011-11-14 | Seattle Genetics Inc | Auristatinkonjugater og deres anvendelse til behandling af cancer, en autoimmun sygdom eller en infektiøs sygdom |
| US20040138269A1 (en) | 2002-10-11 | 2004-07-15 | Sugen, Inc. | Substituted pyrroles as kinase inhibitors |
| GB0226593D0 (en) | 2002-11-14 | 2002-12-24 | Consultants Ltd | Compounds |
| ATE421967T1 (de) | 2003-03-31 | 2009-02-15 | Council Scient Ind Res | Nichtvernetzende pyrroloä2,1-cüä1, 4übenzodiazepine als potentielle antitumor- agentien und ihre herstellung |
| GB0321295D0 (en) | 2003-09-11 | 2003-10-15 | Spirogen Ltd | Synthesis of protected pyrrolobenzodiazepines |
| WO2005040170A2 (en) | 2003-10-22 | 2005-05-06 | Government Of The United States Of America, Represented By The Secretary, Department Of Health And Human Services | Pyrrolobenzodiazepine derivatives, compositions comprising the same and methods related thereto |
| GB0416511D0 (en) | 2003-10-22 | 2004-08-25 | Spirogen Ltd | Pyrrolobenzodiazepines |
| CN107213469A (zh) | 2003-11-06 | 2017-09-29 | 西雅图基因公司 | 能够与配体偶联的单甲基缬氨酸化合物 |
| EP1718667B1 (en) | 2004-02-23 | 2013-01-09 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
| CA2558195C (en) * | 2004-03-01 | 2012-11-06 | Spirogen Limited | 11-hydroxy-5h-pyrrolo[2,1-c][1,4]benzodiazepin-5-one derivatives as key intermediates for the preparation of c2 substituted pyrrolobenzodiazepines |
| GB0404574D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Amino acids |
| GB0404578D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0404577D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| DE102004010943A1 (de) | 2004-03-03 | 2005-09-29 | Degussa Ag | Verfahren zur Herstellung von N-geschützten 4-Ketprolinderivaten |
| US7528126B2 (en) | 2004-03-09 | 2009-05-05 | Spirogen Limited | Pyrrolobenzodiazepines |
| FR2869231B1 (fr) | 2004-04-27 | 2008-03-14 | Sod Conseils Rech Applic | Composition therapeutique contenant au moins un derive de la pyrrolobenzodiazepine et la fludarabine |
| GB0410725D0 (en) | 2004-05-13 | 2004-06-16 | Spirogen Ltd | Pyrrolobenzodiazepine therapeutic agents |
| KR101270829B1 (ko) | 2004-09-23 | 2013-06-07 | 제넨테크, 인크. | 시스테인 유전자조작 항체 및 접합체 |
| EP1831418A2 (en) | 2004-12-24 | 2007-09-12 | Showa Denko Kabushiki Kaisha | Production method of thermoelectric semiconductor alloy, thermoelectric conversion module and thermoelectric power generating device |
| CN101203241B (zh) | 2005-04-19 | 2012-02-22 | 西雅图基因公司 | 人源化抗-cd70结合物和其应用 |
| GB0508084D0 (en) * | 2005-04-21 | 2005-06-01 | Spirogen Ltd | Pyrrolobenzodiazepines |
| NZ563136A (en) | 2005-04-21 | 2009-11-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
| US8637664B2 (en) | 2005-10-05 | 2014-01-28 | Spirogen Sarl | Alkyl 4- [4- (5-oxo-2,3,5, 11a-tetrahydo-5H-pyrrolo [2, 1-c] [1,4] benzodiazepine-8-yloxy)-butyrylamino]-1H-pyrrole-2-carboxylate derivatives and related compounds for the treatment of a proliferative disease |
| US20070154906A1 (en) | 2005-10-05 | 2007-07-05 | Spirogen Ltd. | Methods to identify therapeutic candidates |
| SI1813614T1 (sl) | 2006-01-25 | 2012-01-31 | Sanofi 174 | Citotoksična sredstva, ki obsegajo nove tomajmicinske derivate |
| NZ574215A (en) | 2006-07-18 | 2012-07-27 | Sanofi Aventis | Antagonist antibody against epha2 for the treatment of cancer |
| EP1914242A1 (en) | 2006-10-19 | 2008-04-23 | Sanofi-Aventis | Novel anti-CD38 antibodies for the treatment of cancer |
| WO2008050140A2 (en) | 2006-10-27 | 2008-05-02 | Spirogen Limited | Compounds for treatment of parasitic infection |
| DK2099823T4 (da) | 2006-12-01 | 2022-05-09 | Seagen Inc | Målbindingsmiddelvarianter og anvendelser deraf |
| US8465883B2 (en) | 2007-07-11 | 2013-06-18 | The Regents Of The University Of California | Nanostructured polymer membranes for proton conduction |
| SI2019104T1 (sl) | 2007-07-19 | 2013-12-31 | Sanofi | Citotoksična sredstva, ki obsegajo nove tomaimicinske derivate, in njihova terapevtska uporaba |
| GB0722087D0 (en) | 2007-11-09 | 2007-12-19 | Spirogen Ltd | Polyamides |
| GB0722088D0 (en) | 2007-11-09 | 2007-12-19 | Spirogen Ltd | Pyrrolobenzodiazepines |
| US20090310707A1 (en) | 2008-06-17 | 2009-12-17 | Jung-Fu Cheng | Transmitter and method for transmitting soft pilot symbols in a digital communication system |
| GB0813432D0 (en) | 2008-07-22 | 2008-08-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0819095D0 (en) * | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0819097D0 (en) | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| SG173152A1 (en) | 2009-02-05 | 2011-08-29 | Immunogen Inc | Novel benzodiazepine derivatives |
| FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
| EP2480230A4 (en) | 2009-09-24 | 2015-06-10 | Seattle Genetics Inc | DR5 Ligand-HEILMITTELKONJUGATE |
| US9040526B2 (en) | 2010-02-09 | 2015-05-26 | Bristol-Myers Squibb Company | Benzylpyrrolidinone derivatives as modulators of chemokine receptor activity |
| 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 |
| WO2011130598A1 (en) | 2010-04-15 | 2011-10-20 | Spirogen Limited | Pyrrolobenzodiazepines and conjugates thereof |
| KR101772354B1 (ko) | 2010-04-15 | 2017-08-28 | 시애틀 지네틱스, 인크. | 표적화된 피롤로벤조디아제핀 접합체 |
| KR20190089048A (ko) | 2011-02-15 | 2019-07-29 | 이뮤노젠 아이엔씨 | 컨쥬게이트의 제조방법 |
| WO2013041606A1 (en) | 2011-09-20 | 2013-03-28 | Spirogen Sàrl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
| WO2013055987A1 (en) | 2011-10-14 | 2013-04-18 | Spirogen Sàrl | Pyrrolobenzodiazepines and conjugates thereof |
| BR112014008888A2 (pt) | 2011-10-14 | 2017-04-18 | Seattle Genetics Inc | pirrolobenzodiazepinas |
| US9388187B2 (en) | 2011-10-14 | 2016-07-12 | Medimmune Limited | Pyrrolobenzodiazepines |
| US9526798B2 (en) | 2011-10-14 | 2016-12-27 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| MX358757B (es) | 2011-10-14 | 2018-09-03 | Seattle Genetics Inc | Pirrolobenzodiazepinas y conjugados dirigidos. |
| EP2751076B1 (en) | 2011-10-14 | 2018-04-25 | MedImmune Limited | Synthesis method and intermediates useful in the preparation of pyrrolobenzodiazepines |
| NZ701290A (en) | 2012-04-30 | 2016-08-26 | Medimmune Ltd | Pyrrolobenzodiazepines |
| KR101960130B1 (ko) | 2012-04-30 | 2019-03-19 | 메디뮨 리미티드 | 피롤로벤조디아제핀 |
| TW201406785A (zh) | 2012-07-09 | 2014-02-16 | Genentech Inc | 抗ｃｄ２２抗體及免疫結合物 |
| IN2014DN10652A (enExample) | 2012-07-09 | 2015-09-11 | Genentech Inc | |
| BR112015002193A2 (pt) | 2012-08-02 | 2017-07-04 | Genentech Inc | anticorpos anti-etbr e imunoconjugados |
| WO2014057118A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sarl | Pyrrolobenzodiazepine-anti-cd22 antibody conjugates |
| AU2013328673B2 (en) | 2012-10-12 | 2017-07-13 | Medimmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
| HRP20171264T1 (hr) | 2012-10-12 | 2017-10-20 | Adc Therapeutics Sa | Konjugati protutijela anti-her2-pirolobenzodiazepina |
| HRP20190366T1 (hr) | 2012-10-12 | 2019-04-19 | Medimmune Limited | Pirolobenzodiazepini i njihovi konjugati |
| HRP20181646T2 (hr) | 2012-10-12 | 2019-08-09 | Adc Therapeutics Sa | Konjugati pirolobenzodiazepin - anti-psma protutijela |
| PL2906251T3 (pl) | 2012-10-12 | 2018-02-28 | Adc Therapeutics Sa | Koniugaty pirolobenzodiazepina-przeciwciało anty-CD22 |
| KR101645905B1 (ko) | 2012-10-12 | 2016-08-04 | 스피로즌 살 | 피롤로벤조디아제핀 및 그의 컨주게이트 |
| WO2014057117A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| ES2680153T3 (es) | 2012-10-12 | 2018-09-04 | Adc Therapeutics Sa | Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas |
| WO2014057120A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| MX364328B (es) | 2012-10-12 | 2019-04-23 | Medimmune Ltd | Conjugados del anticuerpo pirrolobenzodiazepina. |
| CN105246894A (zh) | 2012-12-21 | 2016-01-13 | 斯皮罗根有限公司 | 用于治疗增殖性和自身免疫疾病的非对称吡咯并苯并二氮杂卓二聚物 |
| AU2013366493B2 (en) | 2012-12-21 | 2017-08-24 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| RU2019109456A (ru) | 2013-02-22 | 2019-04-10 | ЭББВИ СТЕМСЕНТРКС ЭлЭлСи | Новые конъюгаты антител и их применения |
| WO2014140862A2 (en) | 2013-03-13 | 2014-09-18 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| EP2968585B1 (en) | 2013-03-13 | 2018-07-18 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| JP6445519B2 (ja) | 2013-03-13 | 2018-12-26 | メドイミューン・リミテッドＭｅｄＩｍｍｕｎｅ Ｌｉｍｉｔｅｄ | ピロロベンゾジアゼピン及びそのコンジュゲート |
| WO2014174111A1 (en) | 2013-04-26 | 2014-10-30 | Pierre Fabre Medicament | Axl antibody-drug conjugate and its use for the treatment of cancer |
| US9950078B2 (en) | 2013-10-11 | 2018-04-24 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| EP3054986B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| EP3054984A1 (en) | 2013-10-11 | 2016-08-17 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| US10010624B2 (en) | 2013-10-11 | 2018-07-03 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| MX381017B (es) | 2013-12-16 | 2025-03-12 | Genentech Inc | Compuestos peptidomiméticos y conjugados anticuerpo-fármaco de estos. |
| GB201406767D0 (en) | 2014-04-15 | 2014-05-28 | Cancer Rec Tech Ltd | Humanized anti-Tn-MUC1 antibodies anf their conjugates |
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- 2012-10-12 BR BR112014008888A patent/BR112014008888A2/pt not_active Application Discontinuation
- 2012-10-12 SG SG11201401021TA patent/SG11201401021TA/en unknown
- 2012-10-12 MX MX2014004557A patent/MX341523B/es active IP Right Grant
- 2012-10-12 CA CA2850103A patent/CA2850103C/en not_active Expired - Fee Related
- 2012-10-12 EA EA201490535A patent/EA028457B1/ru unknown
- 2012-10-12 EP EP12772782.4A patent/EP2751111B1/en not_active Not-in-force
- 2012-10-12 AU AU2012322934A patent/AU2012322934B2/en not_active Ceased
- 2012-10-12 KR KR1020147012411A patent/KR101891859B1/ko not_active Expired - Fee Related
- 2012-10-12 WO PCT/EP2012/070233 patent/WO2013053873A1/en not_active Ceased
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Also Published As
| Publication number | Publication date |
|---|---|
| JP6170497B2 (ja) | 2017-07-26 |
| CN103998450B (zh) | 2017-03-08 |
| WO2013053873A1 (en) | 2013-04-18 |
| CA2850103A1 (en) | 2013-04-18 |
| EA201490535A1 (ru) | 2014-09-30 |
| BR112014008888A2 (pt) | 2017-04-18 |
| CN103998450A (zh) | 2014-08-20 |
| MX341523B (es) | 2016-08-24 |
| KR20140099449A (ko) | 2014-08-12 |
| MX2014004557A (es) | 2015-02-12 |
| JP2014528467A (ja) | 2014-10-27 |
| AU2012322934A1 (en) | 2014-05-29 |
| EP2751111B1 (en) | 2017-04-26 |
| SG11201401021TA (en) | 2014-08-28 |
| AU2012322934B2 (en) | 2016-09-08 |
| EA028457B1 (ru) | 2017-11-30 |
| US9399073B2 (en) | 2016-07-26 |
| KR101891859B1 (ko) | 2018-08-24 |
| EP2751111A1 (en) | 2014-07-09 |
| US20140274907A1 (en) | 2014-09-18 |
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