JP6367204B2 - 結合用のピロロベンゾジアゼピン誘導体の合成および中間体 - Google Patents
結合用のピロロベンゾジアゼピン誘導体の合成および中間体 Download PDFInfo
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- JP6367204B2 JP6367204B2 JP2015536138A JP2015536138A JP6367204B2 JP 6367204 B2 JP6367204 B2 JP 6367204B2 JP 2015536138 A JP2015536138 A JP 2015536138A JP 2015536138 A JP2015536138 A JP 2015536138A JP 6367204 B2 JP6367204 B2 JP 6367204B2
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- 230000015572 biosynthetic process Effects 0.000 title description 23
- 238000003786 synthesis reaction Methods 0.000 title description 21
- 239000000543 intermediate Substances 0.000 title description 4
- 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 3
- 230000021615 conjugation Effects 0.000 title description 2
- -1 (2-trimethylsilyl) ethoxycarbonyl Chemical group 0.000 claims description 108
- 125000003118 aryl group Chemical group 0.000 claims description 95
- 150000001875 compounds Chemical class 0.000 claims description 73
- 125000000623 heterocyclic group Chemical group 0.000 claims description 51
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- 125000001424 substituent group Chemical group 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 41
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 25
- 125000005843 halogen group Chemical group 0.000 claims description 22
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000003342 alkenyl group Chemical group 0.000 claims description 16
- 125000000304 alkynyl group Chemical group 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 229910052717 sulfur Inorganic materials 0.000 claims description 12
- 108010016626 Dipeptides Proteins 0.000 claims description 11
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 11
- 125000001544 thienyl group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 8
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical group OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 229910052727 yttrium Inorganic materials 0.000 claims description 8
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 claims description 7
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 7
- 230000008878 coupling Effects 0.000 claims description 7
- 238000010168 coupling process Methods 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000002194 synthesizing effect Effects 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 125000000539 amino acid group Chemical group 0.000 claims description 3
- IBAHLNWTOIHLKE-UHFFFAOYSA-N cyano cyanate Chemical compound N#COC#N IBAHLNWTOIHLKE-UHFFFAOYSA-N 0.000 claims description 3
- 125000005519 fluorenylmethyloxycarbonyl group Chemical group 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 125000006681 (C2-C10) alkylene group Chemical group 0.000 claims description 2
- 125000005620 boronic acid group Chemical group 0.000 claims description 2
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 description 66
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- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 34
- 238000004949 mass spectrometry Methods 0.000 description 28
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 23
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- 125000006413 ring segment Chemical group 0.000 description 21
- 239000003242 anti bacterial agent Substances 0.000 description 20
- 229940088710 antibiotic agent Drugs 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000000047 product Substances 0.000 description 19
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- 238000006243 chemical reaction Methods 0.000 description 17
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- 238000002390 rotary evaporation Methods 0.000 description 17
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
- 239000012267 brine Substances 0.000 description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 16
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
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- 235000019439 ethyl acetate Nutrition 0.000 description 15
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 14
- 125000003277 amino group Chemical group 0.000 description 14
- 238000000746 purification Methods 0.000 description 13
- 235000001014 amino acid Nutrition 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- 239000001257 hydrogen Substances 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 150000001413 amino acids Chemical class 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
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- 238000010898 silica gel chromatography Methods 0.000 description 9
- 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 8
- 102000005600 Cathepsins Human genes 0.000 description 8
- 108010084457 Cathepsins Proteins 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 8
- 150000001721 carbon Chemical group 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 235000019253 formic acid Nutrition 0.000 description 8
- 125000005647 linker group Chemical group 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [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 8
- 239000012071 phase Substances 0.000 description 8
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- 229910052786 argon Inorganic materials 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 7
- 239000000178 monomer Substances 0.000 description 7
- 229920006395 saturated elastomer Polymers 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000003545 alkoxy group Chemical group 0.000 description 6
- 238000009739 binding Methods 0.000 description 6
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- 239000011734 sodium Substances 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
- 125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 description 5
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- 125000004122 cyclic group Chemical group 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
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- 125000006239 protecting group Chemical group 0.000 description 5
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- ARKUDJPBDMAVBL-UHFFFAOYSA-N 3-[2-[2-[2-[2-[2-[2-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoic acid Chemical compound OC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCN1C(=O)C=CC1=O ARKUDJPBDMAVBL-UHFFFAOYSA-N 0.000 description 4
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- 125000003368 amide group Chemical group 0.000 description 4
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- KQZMZNLKVKGMJS-JLTOFOAXSA-N (2r)-2-[[(2r)-2-(9h-fluoren-9-ylmethoxycarbonylamino)-3-methylbutanoyl]amino]propanoic acid Chemical compound C1=CC=C2C(COC(=O)N[C@H](C(C)C)C(=O)N[C@H](C)C(O)=O)C3=CC=CC=C3C2=C1 KQZMZNLKVKGMJS-JLTOFOAXSA-N 0.000 description 3
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- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003506 n-propoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])O* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000000018 nitroso group Chemical group N(=O)* 0.000 description 1
- UMRZSTCPUPJPOJ-KNVOCYPGSA-N norbornane Chemical compound C1C[C@H]2CC[C@@H]1C2 UMRZSTCPUPJPOJ-KNVOCYPGSA-N 0.000 description 1
- NIHNNTQXNPWCJQ-UHFFFAOYSA-N o-biphenylenemethane Natural products C1=CC=C2CC3=CC=CC=C3C2=C1 NIHNNTQXNPWCJQ-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- GHCAUEMXBSLMGU-UHFFFAOYSA-N oxadiazole;1,2,5-oxadiazole Chemical compound C=1C=NON=1.C1=CON=N1 GHCAUEMXBSLMGU-UHFFFAOYSA-N 0.000 description 1
- NFBOHOGPQUYFRF-UHFFFAOYSA-N oxanthrene Chemical compound C1=CC=C2OC3=CC=CC=C3OC2=C1 NFBOHOGPQUYFRF-UHFFFAOYSA-N 0.000 description 1
- AZHVQJLDOFKHPZ-UHFFFAOYSA-N oxathiazine Chemical compound O1SN=CC=C1 AZHVQJLDOFKHPZ-UHFFFAOYSA-N 0.000 description 1
- CQDAMYNQINDRQC-UHFFFAOYSA-N oxatriazole Chemical compound C1=NN=NO1 CQDAMYNQINDRQC-UHFFFAOYSA-N 0.000 description 1
- ATYBXHSAIOKLMG-UHFFFAOYSA-N oxepin Chemical compound O1C=CC=CC=C1 ATYBXHSAIOKLMG-UHFFFAOYSA-N 0.000 description 1
- AHHWIHXENZJRFG-UHFFFAOYSA-N oxetane Chemical compound C1COC1 AHHWIHXENZJRFG-UHFFFAOYSA-N 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- AUONHKJOIZSQGR-UHFFFAOYSA-N oxophosphane Chemical compound P=O AUONHKJOIZSQGR-UHFFFAOYSA-N 0.000 description 1
- 125000005740 oxycarbonyl group Chemical group [*:1]OC([*:2])=O 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical class [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 1
- ZOUWOGOTHLRRLS-UHFFFAOYSA-N palladium;phosphane Chemical class P.[Pd] ZOUWOGOTHLRRLS-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 125000004817 pentamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 1
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- 229950000688 phenothiazine Drugs 0.000 description 1
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- UEZVMMHDMIWARA-UHFFFAOYSA-M phosphonate Chemical compound [O-]P(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-M 0.000 description 1
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- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical compound C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
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- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
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- 238000001556 precipitation Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- MTVHIBJYRULMHK-UHFFFAOYSA-N propanamide pyrrole-2,5-dione Chemical compound C(CC)(=O)N.C1(C=CC(N1)=O)=O MTVHIBJYRULMHK-UHFFFAOYSA-N 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical compound N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 150000003214 pyranose derivatives Chemical class 0.000 description 1
- CRTBNOWPBHJICM-UHFFFAOYSA-N pyrazine Chemical compound C1=CN=CC=N1.C1=CN=CC=N1 CRTBNOWPBHJICM-UHFFFAOYSA-N 0.000 description 1
- UBRJWPDONDYLLX-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1.C1CNNC1 UBRJWPDONDYLLX-UHFFFAOYSA-N 0.000 description 1
- IOXGEAHHEGTLMQ-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1.C1=CC=NN=C1 IOXGEAHHEGTLMQ-UHFFFAOYSA-N 0.000 description 1
- YMXFJTUQQVLJEN-UHFFFAOYSA-N pyrimidine Chemical compound C1=CN=CN=C1.C1=CN=CN=C1 YMXFJTUQQVLJEN-UHFFFAOYSA-N 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 description 1
- 125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
- 125000004549 quinolin-4-yl group Chemical group N1=CC=C(C2=CC=CC=C12)* 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910001923 silver oxide Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- YYMWVZQRBNARFZ-UHFFFAOYSA-M sodium;2-[2,3-bis(sulfanyl)propoxy]ethanesulfonate Chemical compound [Na+].[O-]S(=O)(=O)CCOCC(S)CS YYMWVZQRBNARFZ-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
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- 229960002317 succinimide Drugs 0.000 description 1
- BUUPQKDIAURBJP-UHFFFAOYSA-N sulfinic acid Chemical compound OS=O BUUPQKDIAURBJP-UHFFFAOYSA-N 0.000 description 1
- 125000000213 sulfino group Chemical group [H]OS(*)=O 0.000 description 1
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 1
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- 125000000565 sulfonamide group Chemical group 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
- 125000001174 sulfone group Chemical group 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 125000003666 tauryl group Chemical group [H]N([H])C([H])([H])C([H])([H])S(*)(=O)=O 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000037 tert-butyldiphenylsilyl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1[Si]([H])([*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- IFLREYGFSNHWGE-UHFFFAOYSA-N tetracene Chemical compound C1=CC=CC2=CC3=CC4=CC=CC=C4C=C3C=C21 IFLREYGFSNHWGE-UHFFFAOYSA-N 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- KHVCOYGKHDJPBZ-WDCZJNDASA-N tetrahydrooxazine Chemical compound OC[C@H]1ONC[C@@H](O)[C@@H]1O KHVCOYGKHDJPBZ-WDCZJNDASA-N 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 150000003536 tetrazoles Chemical class 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- GVIJJXMXTUZIOD-UHFFFAOYSA-N thianthrene Chemical compound C1=CC=C2SC3=CC=CC=C3SC2=C1 GVIJJXMXTUZIOD-UHFFFAOYSA-N 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- JWCVYQRPINPYQJ-UHFFFAOYSA-N thiepane Chemical compound C1CCCSCC1 JWCVYQRPINPYQJ-UHFFFAOYSA-N 0.000 description 1
- XSROQCDVUIHRSI-UHFFFAOYSA-N thietane Chemical compound C1CSC1 XSROQCDVUIHRSI-UHFFFAOYSA-N 0.000 description 1
- VOVUARRWDCVURC-UHFFFAOYSA-N thiirane Chemical compound C1CS1 VOVUARRWDCVURC-UHFFFAOYSA-N 0.000 description 1
- 125000005300 thiocarboxy group Chemical group C(=S)(O)* 0.000 description 1
- 150000003566 thiocarboxylic acids Chemical class 0.000 description 1
- 125000000858 thiocyanato group Chemical group *SC#N 0.000 description 1
- 125000005031 thiocyano group Chemical group S(C#N)* 0.000 description 1
- BQAJJINKFRRSFO-UHFFFAOYSA-N thiolane Chemical compound C1CCSC1.C1CCSC1 BQAJJINKFRRSFO-UHFFFAOYSA-N 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229940113082 thymine Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 229940062627 tribasic potassium phosphate Drugs 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- 238000004724 ultra fast liquid chromatography Methods 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 229940035893 uracil Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 238000010792 warming Methods 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
- 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
- A61K47/62—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
-
- 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
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06043—Leu-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biophysics (AREA)
- Genetics & Genomics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261713083P | 2012-10-12 | 2012-10-12 | |
| US61/713,083 | 2012-10-12 | ||
| PCT/EP2013/071234 WO2014057072A1 (en) | 2012-10-12 | 2013-10-11 | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2015534574A JP2015534574A (ja) | 2015-12-03 |
| JP2015534574A5 JP2015534574A5 (enExample) | 2016-12-01 |
| JP6367204B2 true JP6367204B2 (ja) | 2018-08-01 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015536138A Expired - Fee Related JP6367204B2 (ja) | 2012-10-12 | 2013-10-11 | 結合用のピロロベンゾジアゼピン誘導体の合成および中間体 |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US9745303B2 (enExample) |
| EP (1) | EP2906249B1 (enExample) |
| JP (1) | JP6367204B2 (enExample) |
| AU (1) | AU2013328673B2 (enExample) |
| CA (1) | CA2885305C (enExample) |
| WO (1) | WO2014057072A1 (enExample) |
Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0819095D0 (en) | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| JP5875083B2 (ja) | 2010-04-15 | 2016-03-02 | メディミューン リミテッド | 増殖性疾患治療用ピロロベンゾジアゼピン |
| CA2795349C (en) | 2010-04-15 | 2016-11-29 | Seattle Genetics, Inc. | Targeted pyrrolobenzodiazepine conjugates |
| SG11201400770SA (en) | 2011-09-20 | 2014-04-28 | Spirogen Sarl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
| AU2012322932B2 (en) | 2011-10-14 | 2016-11-10 | Medimmune Limited | Pyrrolobenzodiazepines |
| CA2850373C (en) | 2011-10-14 | 2019-07-16 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| CN103997893B (zh) | 2011-10-14 | 2019-04-12 | 西雅图基因公司 | 吡咯并苯并二氮杂卓和靶向结合物 |
| EP2751111B1 (en) | 2011-10-14 | 2017-04-26 | MedImmune Limited | Asymmetrical bis-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-5-one) derivatives for the treatment of proliferative or autoimmune diseases |
| MX338711B (es) | 2012-10-12 | 2016-04-28 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas. |
| HRP20182129T1 (hr) | 2012-10-12 | 2019-02-08 | Adc Therapeutics Sa | Konjugati protutijelo - pirolobenzodiazepin |
| EP2906297B1 (en) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| JP6392765B2 (ja) | 2012-10-12 | 2018-09-19 | エイディーシー・セラピューティクス・エス・アーＡｄｃ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｓａ | ピロロベンゾジアゼピン−抗体結合体 |
| RS57694B1 (sr) | 2012-10-12 | 2018-11-30 | Adc Therapeutics Sa | Pirolobenzodiazepin - anti-psma konjugati antitela |
| EP2906296B1 (en) | 2012-10-12 | 2018-03-21 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| EP2906249B1 (en) | 2012-10-12 | 2018-06-27 | MedImmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
| 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 |
| CN105189507A (zh) | 2012-12-21 | 2015-12-23 | 斯皮罗根有限公司 | 吡咯并苯并二氮杂卓及其结合物 |
| CN110627797A (zh) | 2012-12-21 | 2019-12-31 | 麦迪穆有限责任公司 | 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 |
| ES2731681T3 (es) | 2013-02-22 | 2019-11-18 | Abbvie Stemcentrx Llc | Conjugados de anticuerpo anti-DLL3 y PBD y usos de los mismos |
| AU2014229529B2 (en) | 2013-03-13 | 2018-02-15 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| TWI680766B (zh) | 2013-03-13 | 2020-01-01 | 英商梅迪繆思有限公司 | 吡咯并苯并二氮呯及其共軛物 |
| SG11201601424PA (en) | 2013-08-28 | 2016-03-30 | Stemcentrx Inc | Site-specific antibody conjugation methods and compositions |
| WO2015052534A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| EP3054983B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| WO2015052535A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| CA2939941A1 (en) | 2014-02-21 | 2015-08-27 | Abbvie Stemcentrx Llc | Anti-dll3 antibodies and drug conjugates for use in melanoma |
| GB201416112D0 (en) | 2014-09-12 | 2014-10-29 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| LT3191135T (lt) | 2014-09-12 | 2020-11-25 | Genentech, Inc. | Anti-her2 antikūnai ir imunokonjugatai |
| CN107148285B (zh) | 2014-11-25 | 2022-01-04 | Adc治疗股份有限公司 | 吡咯并苯并二氮杂䓬-抗体缀合物 |
| GB201506402D0 (en) | 2015-04-15 | 2015-05-27 | Berkel Patricius H C Van And Howard Philip W | Site-specific antibody-drug conjugates |
| GB201506411D0 (en) | 2015-04-15 | 2015-05-27 | Bergenbio As | Humanized anti-axl antibodies |
| CR20180243A (es) | 2015-10-02 | 2018-07-31 | Genentech Inc | Conjugados de anticuerpo-fármaco de pirrolobenzodiazepina y métodos de uso |
| 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 |
| GB201607478D0 (en) | 2016-04-29 | 2016-06-15 | Medimmune Ltd | Pyrrolobenzodiazepine Conjugates |
| GB201617466D0 (en) | 2016-10-14 | 2016-11-30 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
| GB201619490D0 (en) * | 2016-11-17 | 2017-01-04 | Medimmune Ltd | Pyrrolobenzodiazepine conjugates |
| RS61795B1 (sr) | 2017-02-08 | 2021-06-30 | Adc Therapeutics Sa | Konjugati pirolobenzodiazepin antitela |
| GB201702031D0 (en) | 2017-02-08 | 2017-03-22 | Medlmmune Ltd | Pyrrolobenzodiazepine-antibody conjugates |
| CN110582505B (zh) | 2017-04-18 | 2021-04-02 | 免疫医疗有限公司 | 吡咯并苯并二氮杂*缀合物 |
| WO2018193102A1 (en) | 2017-04-20 | 2018-10-25 | Adc Therapeutics Sa | Combination therapy with an anti-axl antibody-drug conjugate |
| CA3064804A1 (en) | 2017-06-14 | 2018-12-20 | Adc Therapeutics Sa | Dosage regimes for the administration of an anti-cd19 adc |
| KR102270107B1 (ko) | 2017-08-18 | 2021-06-30 | 메디뮨 리미티드 | 피롤로벤조디아제핀 컨쥬게이트 |
| NZ762505A (en) | 2017-09-29 | 2026-03-27 | Daiichi Sankyo Co Ltd | Antibody-pyrrolobenzodiazepine derivative conjugate |
| GB201803342D0 (en) | 2018-03-01 | 2018-04-18 | Medimmune Ltd | Methods |
| GB201806022D0 (en) | 2018-04-12 | 2018-05-30 | Medimmune Ltd | Pyrrolobenzodiazepines and conjugates thereof |
| CN113631560B (zh) | 2019-03-15 | 2025-02-18 | 麦迪穆有限责任公司 | 氮杂环丁烷并苯并二氮杂䓬二聚体和用于治疗癌症的包含它们的缀合物 |
| EP4548932A1 (en) | 2022-06-30 | 2025-05-07 | Toray Industries, Inc. | Pharmaceutical composition for treating and/or preventing cancer |
Family Cites Families (133)
| 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 |
| JPS4843755B1 (enExample) | 1969-06-26 | 1973-12-20 | ||
| IL33558A (en) | 1968-12-30 | 1973-10-25 | Fujisawa Pharmaceutical Co | Antibiotic pyrrolo-benzodiazepine compound,its derivatives and processes for their production |
| DE1965304A1 (de) | 1968-12-30 | 1970-07-23 | Fujisawa Pharmaceutical Co | Benzdiazepinon-Verbindungen und Verfahren zu ihrer Herstellung |
| JPS6053033B2 (ja) | 1976-12-28 | 1985-11-22 | 財団法人微生物化学研究会 | 新制癌抗生物質マゼスラマイシン及びその製造方法 |
| 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 |
| JPS57131791A (en) | 1980-12-31 | 1982-08-14 | Fujisawa Pharmaceut Co Ltd | Benzodiazepine derivative and its preparation |
| CA1173441A (en) | 1981-02-27 | 1984-08-28 | Hoffmann-La Roche Limited | Imidazodiazepines |
| CA1185602A (en) | 1981-02-27 | 1985-04-16 | Emilio Kyburz | Imidazodiazepines |
| CA1184175A (en) | 1981-02-27 | 1985-03-19 | Walter Hunkeler | 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 |
| 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 |
| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
| 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 |
| US5583024A (en) | 1985-12-02 | 1996-12-10 | The Regents Of The University Of California | Recombinant expression of Coleoptera luciferase |
| 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 |
| AU2115695A (en) | 1994-03-10 | 1995-09-25 | G.D. Searle & Co. | L-n6-(1-iminoethyl)lysine derivatives useful as nitric oxide synthase inhibitors |
| JPH08336393A (ja) | 1995-04-13 | 1996-12-24 | Mitsubishi Chem Corp | 光学活性なγ−置換−β−ヒドロキシ酪酸エステルの製造法 |
| EP1093600B1 (en) | 1998-07-08 | 2004-09-15 | E Ink Corporation | Methods for achieving improved color in microencapsulated electrophoretic devices |
| GB9818730D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collections of compounds |
| GB9818731D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Compounds |
| GB9818732D0 (en) | 1998-08-27 | 1998-10-21 | Univ Portsmouth | Collection of compounds |
| DE69925133T2 (de) | 1998-08-27 | 2006-01-19 | Spirogen Ltd., Ryde | Pyrrolobenzodiazepine |
| US6909006B1 (en) | 1999-08-27 | 2005-06-21 | Spirogen Limited | Cyclopropylindole derivatives |
| WO2002030894A2 (en) | 2000-09-19 | 2002-04-18 | Taiho Pharmaceutical Co., Ltd. | Compositions and methods of the use thereof achiral analogues of cc-1065 and the duocarmycins |
| US6362331B1 (en) | 2001-03-30 | 2002-03-26 | Council Of Scientific And Industrial Research | Process for the preparation of antitumor agents |
| EP1401850A1 (en) | 2001-06-20 | 2004-03-31 | Nuevolution A/S | Nucleoside derivatives for library preparation |
| 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 |
| EP2478912B1 (en) | 2003-11-06 | 2016-08-31 | Seattle Genetics, Inc. | Auristatin conjugates with anti-HER2 or anti-CD22 antibodies and their use in therapy |
| EP1720908A2 (en) | 2004-02-17 | 2006-11-15 | Absalus, Inc. | Super-humanized antibodies against respiratory syncytial virus |
| CA2556752C (en) | 2004-02-23 | 2016-02-02 | Genentech, Inc. | Heterocyclic self-immolative linkers and conjugates |
| GB0404577D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0404578D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0404574D0 (en) | 2004-03-01 | 2004-04-07 | Spirogen Ltd | Amino acids |
| WO2005085251A1 (en) | 2004-03-01 | 2005-09-15 | 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 |
| DE102004010943A1 (de) | 2004-03-03 | 2005-09-29 | Degussa Ag | Verfahren zur Herstellung von N-geschützten 4-Ketprolinderivaten |
| WO2005085260A1 (en) | 2004-03-09 | 2005-09-15 | 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 |
| DK1791565T3 (en) | 2004-09-23 | 2016-08-01 | Genentech Inc | Cysteingensplejsede antibodies and conjugates |
| US7849909B2 (en) | 2004-12-24 | 2010-12-14 | Showa Denko K.K. | Production method of thermoelectric semiconductor alloy, thermoelectric conversion module and thermoelectric power generating device |
| JP5122441B2 (ja) | 2005-04-19 | 2013-01-16 | シアトル ジェネティックス， インコーポレイテッド | ヒト化抗ｃｄ７０結合剤およびその使用 |
| US7612062B2 (en) | 2005-04-21 | 2009-11-03 | Spirogen Limited | Pyrrolobenzodiazepines |
| US20070154906A1 (en) | 2005-10-05 | 2007-07-05 | Spirogen Ltd. | Methods to identify therapeutic candidates |
| 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 |
| RS52060B (sr) | 2006-01-25 | 2012-04-30 | Sanofi | Citotoksični agensi koji sadrže nove derivate tomaimicina |
| MX2009000709A (es) | 2006-07-18 | 2009-02-04 | Sanofi Aventis | Anticuerpo antagonista contra epha2 para el tratamiento de cancer. |
| US10144736B2 (en) * | 2006-07-20 | 2018-12-04 | Gilead Sciences, Inc. | Substituted pteridines useful for the treatment and prevention of viral infections |
| 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 |
| PT2099823E (pt) | 2006-12-01 | 2014-12-22 | Seattle Genetics Inc | Agentes de ligação ao alvo variantes e suas utilizações |
| JP2008291207A (ja) | 2007-04-27 | 2008-12-04 | Kyowa Hakko Kirin Co Ltd | 塩基性アミノ酸を有するらせん状ポリマー |
| CL2008001334A1 (es) | 2007-05-08 | 2008-09-22 | Genentech Inc | Anticuerpo anti-muc16 disenado con cisteina; conjugado que lo comprende; metodo de produccion; formulacion farmaceutica que lo comprende; y su uso para tratar el cancer. |
| SI2019104T1 (sl) | 2007-07-19 | 2013-12-31 | Sanofi | Citotoksična sredstva, ki obsegajo nove tomaimicinske derivate, in njihova terapevtska uporaba |
| GB0716799D0 (en) | 2007-08-31 | 2007-10-10 | Univ Kent Canterbury | Improvements in or relating to radio-labelled peptides |
| NZ584514A (en) | 2007-10-19 | 2012-07-27 | Genentech Inc | Cysteine engineered anti-tenb2 antibodies and antibody drug conjugates |
| GB0722088D0 (en) | 2007-11-09 | 2007-12-19 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0722087D0 (en) | 2007-11-09 | 2007-12-19 | Spirogen Ltd | Polyamides |
| DK2265283T3 (da) | 2008-03-18 | 2014-10-20 | Seattle Genetics Inc | Auristatin-lægemiddel-linker-konjugater |
| GB0813432D0 (en) | 2008-07-22 | 2008-08-27 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0819097D0 (en) | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| GB0819095D0 (en) | 2008-10-17 | 2008-11-26 | Spirogen Ltd | Pyrrolobenzodiazepines |
| US20110077365A1 (en) * | 2008-12-29 | 2011-03-31 | Gilbert Yu | Preparation of organosilicon-containing triazoles |
| RU2683325C2 (ru) | 2009-02-05 | 2019-03-28 | Иммьюноджен, Инк. | Новые производные бензодиазепина |
| CN101492494A (zh) | 2009-03-05 | 2009-07-29 | 浙江大学 | 整合素配体环肽类似物及其环化方法 |
| FR2949469A1 (fr) | 2009-08-25 | 2011-03-04 | Sanofi Aventis | Derives anticancereux, leur preparation et leur application en therapeutique |
| PL2479165T3 (pl) * | 2009-09-16 | 2018-05-30 | Astellas Pharma Inc. | Związek glicynowy |
| JP2013505944A (ja) | 2009-09-24 | 2013-02-21 | シアトル ジェネティックス， インコーポレイテッド | Ｄｒ５リガンド薬物結合体 |
| US9040526B2 (en) | 2010-02-09 | 2015-05-26 | Bristol-Myers Squibb Company | Benzylpyrrolidinone derivatives as modulators of chemokine receptor activity |
| CA2795349C (en) | 2010-04-15 | 2016-11-29 | Seattle Genetics, Inc. | Targeted pyrrolobenzodiazepine conjugates |
| SI2528625T1 (sl) | 2010-04-15 | 2013-11-29 | Spirogen Sarl | Pirolobenzodiazepini in njihovi konjugati |
| JP5875083B2 (ja) | 2010-04-15 | 2016-03-02 | メディミューン リミテッド | 増殖性疾患治療用ピロロベンゾジアゼピン |
| WO2011130615A2 (en) | 2010-04-15 | 2011-10-20 | Dr. Reddy's Laboratories Ltd. | Preparation of lacosamide |
| GB201006340D0 (en) | 2010-04-15 | 2010-06-02 | Spirogen Ltd | Synthesis method and intermediates |
| ES2582471T3 (es) * | 2011-02-07 | 2016-09-13 | Rempex Pharmaceuticals, Inc. | Inhibidores polibásicos de la bomba de flujo de salida bacteriana que contienen boro y usos terapéuticos de los mismos |
| JP5826863B2 (ja) | 2011-02-15 | 2015-12-02 | イミュノジェン・インコーポレーテッド | 細胞傷害性ベンゾジアゼピン誘導体 |
| SG11201400770SA (en) * | 2011-09-20 | 2014-04-28 | Spirogen Sarl | Pyrrolobenzodiazepines as unsymmetrical dimeric pbd compounds for inclusion in targeted conjugates |
| CN103997893B (zh) | 2011-10-14 | 2019-04-12 | 西雅图基因公司 | 吡咯并苯并二氮杂卓和靶向结合物 |
| BR112014009070B1 (pt) | 2011-10-14 | 2021-11-23 | Medimmune Limited | Método de síntese e intermediários úteis na preparação de pirrolobenzo-diazepinas |
| EP2751111B1 (en) | 2011-10-14 | 2017-04-26 | MedImmune Limited | Asymmetrical bis-(5H-Pyrrolo[2,1-c][1,4]benzodiazepin-5-one) derivatives for the treatment of proliferative or autoimmune diseases |
| AU2012322932B2 (en) | 2011-10-14 | 2016-11-10 | Medimmune Limited | Pyrrolobenzodiazepines |
| CA2850373C (en) | 2011-10-14 | 2019-07-16 | Seattle Genetics, Inc. | Pyrrolobenzodiazepines and targeted conjugates |
| BR112014009050B1 (pt) | 2011-10-14 | 2022-06-21 | Medimmune Limited | Conjugado anticorpo-fármaco de pirrolbenzodiazepinas, composição farmacêutica que compreende o mesmo, bem como compostos de pirrolbenzodiazepinas |
| US20150024037A1 (en) | 2012-02-16 | 2015-01-22 | The University Of Toledo | Xenoantigen-Displaying Anti-Cancer Vaccines and Method of Making |
| FR2989085A1 (fr) | 2012-04-05 | 2013-10-11 | Commissariat Energie Atomique | Radiotraceurs, procedes de preparation et applications |
| AU2013255612B2 (en) | 2012-04-30 | 2017-06-22 | Medimmune Limited | Pyrrolobenzodiazepines |
| ES2623042T3 (es) | 2012-04-30 | 2017-07-10 | Medimmune Limited | Pirrolobenzodiacepinas |
| IN2014DN10652A (enExample) | 2012-07-09 | 2015-09-11 | Genentech Inc | |
| AR091703A1 (es) | 2012-07-09 | 2015-02-25 | Genentech Inc | Anticuerpos e inmunoconjugados que comprenden anticuerpos anti-cd22 |
| JP2015528818A (ja) | 2012-08-02 | 2015-10-01 | ジェネンテック， インコーポレイテッド | 抗ｅｔｂｒ抗体およびイムノコンジュゲート |
| EP2906249B1 (en) | 2012-10-12 | 2018-06-27 | MedImmune Limited | Synthesis and intermediates of pyrrolobenzodiazepine derivatives for conjugation |
| HRP20190366T1 (hr) | 2012-10-12 | 2019-04-19 | Medimmune Limited | Pirolobenzodiazepini i njihovi konjugati |
| EP2906296B1 (en) | 2012-10-12 | 2018-03-21 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| EP2906297B1 (en) | 2012-10-12 | 2017-12-06 | ADC Therapeutics SA | Pyrrolobenzodiazepine-antibody conjugates |
| JP6392765B2 (ja) | 2012-10-12 | 2018-09-19 | エイディーシー・セラピューティクス・エス・アーＡｄｃ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｓａ | ピロロベンゾジアゼピン−抗体結合体 |
| WO2014057118A1 (en) | 2012-10-12 | 2014-04-17 | Adc Therapeutics Sarl | Pyrrolobenzodiazepine-anti-cd22 antibody conjugates |
| ES2680153T3 (es) | 2012-10-12 | 2018-09-04 | Adc Therapeutics Sa | Conjugados de anticuerpos anti-PSMA-pirrolobenzodiazepinas |
| MX338711B (es) | 2012-10-12 | 2016-04-28 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas. |
| HRP20182129T1 (hr) | 2012-10-12 | 2019-02-08 | Adc Therapeutics Sa | Konjugati protutijelo - pirolobenzodiazepin |
| SI2906252T1 (sl) | 2012-10-12 | 2017-10-30 | Adc Therapeutics Sa | Pirolobenzodiazepin-anti-HER2 protitelesni konjugati |
| RS57694B1 (sr) | 2012-10-12 | 2018-11-30 | Adc Therapeutics Sa | Pirolobenzodiazepin - anti-psma konjugati antitela |
| CN105189507A (zh) | 2012-12-21 | 2015-12-23 | 斯皮罗根有限公司 | 吡咯并苯并二氮杂卓及其结合物 |
| CN110627797A (zh) | 2012-12-21 | 2019-12-31 | 麦迪穆有限责任公司 | 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 |
| ES2731681T3 (es) | 2013-02-22 | 2019-11-18 | Abbvie Stemcentrx Llc | Conjugados de anticuerpo anti-DLL3 y PBD y usos de los mismos |
| TWI680766B (zh) | 2013-03-13 | 2020-01-01 | 英商梅迪繆思有限公司 | 吡咯并苯并二氮呯及其共軛物 |
| AU2014229529B2 (en) | 2013-03-13 | 2018-02-15 | Medimmune Limited | Pyrrolobenzodiazepines and conjugates thereof |
| MX362970B (es) | 2013-03-13 | 2019-02-28 | Medimmune Ltd | Pirrolobenzodiazepinas y conjugados de las mismas. |
| US20160106861A1 (en) | 2013-04-26 | 2016-04-21 | Spirogen Sarl | Axl antibody-drug conjugate and its use for the treatment of cancer |
| WO2015052535A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| WO2015052534A1 (en) | 2013-10-11 | 2015-04-16 | Spirogen Sàrl | Pyrrolobenzodiazepine-antibody conjugates |
| EP3054983B1 (en) | 2013-10-11 | 2019-03-20 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| GB201317981D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| GB201317982D0 (en) | 2013-10-11 | 2013-11-27 | Spirogen Sarl | Pyrrolobenzodiazepines and conjugates thereof |
| US20160256561A1 (en) | 2013-10-11 | 2016-09-08 | Medimmune Limited | Pyrrolobenzodiazepine-antibody conjugates |
| KR102337414B1 (ko) | 2013-12-16 | 2021-12-10 | 제넨테크, 인크. | 펩타이드 모방체 화합물 및 이의 항체-약물 컨쥬게이트 |
| GB201406767D0 (en) | 2014-04-15 | 2014-05-28 | Cancer Rec Tech Ltd | Humanized anti-Tn-MUC1 antibodies anf their conjugates |
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- 2013-10-11 WO PCT/EP2013/071234 patent/WO2014057072A1/en not_active Ceased
- 2013-10-11 CA CA2885305A patent/CA2885305C/en not_active Expired - Fee Related
- 2013-10-11 US US14/434,830 patent/US9745303B2/en not_active Expired - Fee Related
- 2013-10-11 AU AU2013328673A patent/AU2013328673B2/en not_active Ceased
- 2013-10-11 JP JP2015536138A patent/JP6367204B2/ja not_active Expired - Fee Related
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|---|---|
| EP2906249B1 (en) | 2018-06-27 |
| EP2906249A1 (en) | 2015-08-19 |
| WO2014057072A1 (en) | 2014-04-17 |
| US20150274737A1 (en) | 2015-10-01 |
| HK1213488A1 (en) | 2016-09-09 |
| US9745303B2 (en) | 2017-08-29 |
| CA2885305C (en) | 2019-11-12 |
| AU2013328673A1 (en) | 2015-04-02 |
| CA2885305A1 (en) | 2014-04-17 |
| AU2013328673B2 (en) | 2017-07-13 |
| JP2015534574A (ja) | 2015-12-03 |
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