JP2019501131A5 - - Google Patents
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- JP2019501131A5 JP2019501131A5 JP2018526574A JP2018526574A JP2019501131A5 JP 2019501131 A5 JP2019501131 A5 JP 2019501131A5 JP 2018526574 A JP2018526574 A JP 2018526574A JP 2018526574 A JP2018526574 A JP 2018526574A JP 2019501131 A5 JP2019501131 A5 JP 2019501131A5
- Authority
- JP
- Japan
- Prior art keywords
- hydrogen
- subscript
- optionally substituted
- compound
- formula
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 229940079593 drug Drugs 0.000 claims description 201
- 239000003814 drug Substances 0.000 claims description 201
- 229910052739 hydrogen Inorganic materials 0.000 claims description 180
- 239000001257 hydrogen Substances 0.000 claims description 170
- 150000001875 compounds Chemical class 0.000 claims description 156
- 239000003446 ligand Substances 0.000 claims description 147
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 96
- 239000000203 mixture Substances 0.000 claims description 78
- -1 tubulysin compound Chemical class 0.000 claims description 70
- 229910052799 carbon Inorganic materials 0.000 claims description 62
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 61
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
- 239000002253 acid Substances 0.000 claims description 52
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 48
- 239000004472 Lysine Substances 0.000 claims description 48
- 229960003646 lysine Drugs 0.000 claims description 48
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 42
- 150000002431 hydrogen Chemical class 0.000 claims description 42
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 37
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 35
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 32
- 229920001223 polyethylene glycol Polymers 0.000 claims description 30
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 21
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 20
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 17
- 108010016626 Dipeptides Proteins 0.000 claims description 16
- 239000000562 conjugate Substances 0.000 claims description 16
- 125000006239 protecting group Chemical group 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000003107 substituted aryl group Chemical group 0.000 claims description 16
- 210000004027 cell Anatomy 0.000 claims description 15
- 125000005842 heteroatom Chemical group 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 13
- 150000002367 halogens Chemical class 0.000 claims description 13
- 108091005804 Peptidases Proteins 0.000 claims description 12
- 239000004365 Protease Substances 0.000 claims description 12
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims description 11
- 150000001413 amino acids Chemical class 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 150000003839 salts Chemical class 0.000 claims description 10
- 125000004434 sulfur atom Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 9
- 150000001412 amines Chemical class 0.000 claims description 9
- 229940024606 amino acid Drugs 0.000 claims description 9
- 235000001014 amino acid Nutrition 0.000 claims description 9
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 9
- 239000002243 precursor Substances 0.000 claims description 9
- 230000004989 O-glycosylation Effects 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 125000000524 functional group Chemical group 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 208000024891 symptom Diseases 0.000 claims description 8
- 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 7
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 125000005549 heteroarylene group Chemical group 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 102000005744 Glycoside Hydrolases Human genes 0.000 claims description 6
- 108010031186 Glycoside Hydrolases Proteins 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 229940049595 antibody-drug conjugate Drugs 0.000 claims description 6
- 238000003776 cleavage reaction Methods 0.000 claims description 6
- 125000003827 glycol group Chemical group 0.000 claims description 6
- 230000003463 hyperproliferative effect Effects 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 230000007017 scission Effects 0.000 claims description 6
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 5
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 5
- 239000000611 antibody drug conjugate Substances 0.000 claims description 5
- 125000000732 arylene group Chemical group 0.000 claims description 5
- 235000003704 aspartic acid Nutrition 0.000 claims description 5
- 229960005261 aspartic acid Drugs 0.000 claims description 5
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004474 heteroalkylene group Chemical group 0.000 claims description 5
- 210000004881 tumor cell Anatomy 0.000 claims description 5
- 230000002159 abnormal effect Effects 0.000 claims description 4
- 125000000539 amino acid group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 150000001721 carbon Chemical group 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- 230000003834 intracellular effect Effects 0.000 claims description 4
- 238000007363 ring formation reaction Methods 0.000 claims description 4
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 claims description 3
- 239000004475 Arginine Substances 0.000 claims description 3
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 claims description 3
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 claims description 3
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims description 3
- 150000008575 L-amino acids Chemical class 0.000 claims description 3
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 claims description 3
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 claims description 3
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 3
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-GBXIJSLDSA-N L-threonine Chemical compound C[C@@H](O)[C@H](N)C(O)=O AYFVYJQAPQTCCC-GBXIJSLDSA-N 0.000 claims description 3
- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 claims description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 claims description 3
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims description 3
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims description 3
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 claims description 3
- AYFVYJQAPQTCCC-UHFFFAOYSA-N Threonine Natural products CC(O)C(N)C(O)=O AYFVYJQAPQTCCC-UHFFFAOYSA-N 0.000 claims description 3
- 239000004473 Threonine Substances 0.000 claims description 3
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 claims description 3
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 3
- 229960003121 arginine Drugs 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 235000018417 cysteine Nutrition 0.000 claims description 3
- 229960002433 cysteine Drugs 0.000 claims description 3
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 claims description 3
- 235000013922 glutamic acid Nutrition 0.000 claims description 3
- 239000004220 glutamic acid Substances 0.000 claims description 3
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 claims description 3
- 229960002743 glutamine Drugs 0.000 claims description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 229960003104 ornithine Drugs 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 3
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 210000002966 serum Anatomy 0.000 claims description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 3
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 claims description 2
- 101710160107 Outer membrane protein A Proteins 0.000 claims description 2
- 229940125644 antibody drug Drugs 0.000 claims description 2
- 239000000427 antigen Substances 0.000 claims description 2
- 108091007433 antigens Proteins 0.000 claims description 2
- 102000036639 antigens Human genes 0.000 claims description 2
- 230000006907 apoptotic process Effects 0.000 claims description 2
- 210000004899 c-terminal region Anatomy 0.000 claims description 2
- 235000013477 citrulline Nutrition 0.000 claims description 2
- 229960002173 citrulline Drugs 0.000 claims description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 2
- 238000001990 intravenous administration Methods 0.000 claims description 2
- 238000010253 intravenous injection Methods 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 239000007787 solid Substances 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims description 2
- 229930184737 tubulysin Natural products 0.000 claims 10
- 150000007513 acids Chemical class 0.000 claims 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 6
- 238000009472 formulation Methods 0.000 claims 4
- DLKUYSQUHXBYPB-NSSHGSRYSA-N (2s,4r)-4-[[2-[(1r,3r)-1-acetyloxy-4-methyl-3-[3-methylbutanoyloxymethyl-[(2s,3s)-3-methyl-2-[[(2r)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-(4-methylphenyl)pentanoic acid Chemical class N([C@@H]([C@@H](C)CC)C(=O)N(COC(=O)CC(C)C)[C@H](C[C@@H](OC(C)=O)C=1SC=C(N=1)C(=O)N[C@H](C[C@H](C)C(O)=O)CC=1C=CC(C)=CC=1)C(C)C)C(=O)[C@H]1CCCCN1C DLKUYSQUHXBYPB-NSSHGSRYSA-N 0.000 claims 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 2
- 238000010668 complexation reaction Methods 0.000 claims 2
- 239000000543 intermediate Substances 0.000 claims 2
- 150000003512 tertiary amines Chemical class 0.000 claims 2
- LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 claims 1
- KXSKAZFMTGADIV-UHFFFAOYSA-N 2-[3-(2-hydroxyethoxy)propoxy]ethanol Chemical compound OCCOCCCOCCO KXSKAZFMTGADIV-UHFFFAOYSA-N 0.000 claims 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims 1
- 229940126062 Compound A Drugs 0.000 claims 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 claims 1
- 101000629400 Homo sapiens Mesoderm-specific transcript homolog protein Proteins 0.000 claims 1
- 101000693243 Homo sapiens Paternally-expressed gene 3 protein Proteins 0.000 claims 1
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims 1
- 102100026821 Mesoderm-specific transcript homolog protein Human genes 0.000 claims 1
- 102100025757 Paternally-expressed gene 3 protein Human genes 0.000 claims 1
- 102000035195 Peptidases Human genes 0.000 claims 1
- 150000001408 amides Chemical class 0.000 claims 1
- 235000009582 asparagine Nutrition 0.000 claims 1
- 229960001230 asparagine Drugs 0.000 claims 1
- PBJCAWGYZITJFH-UHFFFAOYSA-N carbamic acid;formic acid Chemical group [O-]C=O.[NH3+]C(O)=O PBJCAWGYZITJFH-UHFFFAOYSA-N 0.000 claims 1
- 239000002131 composite material Substances 0.000 claims 1
- 230000021615 conjugation Effects 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 229960001639 penicillamine Drugs 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 claims 1
- 230000004614 tumor growth Effects 0.000 claims 1
- 238000002370 liquid polymer infiltration Methods 0.000 description 16
- 0 CCCC(C)(*)SC(C(*)C(N1C(*)(*)*CC)=O)C1=O Chemical compound CCCC(C)(*)SC(C(*)C(N1C(*)(*)*CC)=O)C1=O 0.000 description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 125000005647 linker group Chemical group 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
- 125000005346 substituted cycloalkyl group Chemical group 0.000 description 2
- 229960002317 succinimide Drugs 0.000 description 2
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 description 1
- SHZGCJCMOBCMKK-UHFFFAOYSA-N CC(C(C(C1O)O)O)OC1O Chemical compound CC(C(C(C1O)O)O)OC1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N Cc1c[nH]c2c1cccc2 Chemical compound Cc1c[nH]c2c1cccc2 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 description 1
- 108010001267 Protein Subunits Proteins 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021099570A JP7241811B2 (ja) | 2015-12-04 | 2021-06-15 | 四級化チューブリシン化合物の複合体 |
| JP2022084444A JP7559006B2 (ja) | 2015-12-04 | 2022-05-24 | 四級化チューブリシン化合物の複合体 |
Applications Claiming Priority (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562263587P | 2015-12-04 | 2015-12-04 | |
| US201562263578P | 2015-12-04 | 2015-12-04 | |
| US62/263,587 | 2015-12-04 | ||
| US62/263,578 | 2015-12-04 | ||
| US201662309448P | 2016-03-16 | 2016-03-16 | |
| US62/309,448 | 2016-03-16 | ||
| US201662309462P | 2016-03-17 | 2016-03-17 | |
| US62/309,462 | 2016-03-17 | ||
| PCT/US2016/064834 WO2017096311A1 (en) | 2015-12-04 | 2016-12-02 | Conjugates of quaternized tubulysin compounds |
Related Child Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021099570A Division JP7241811B2 (ja) | 2015-12-04 | 2021-06-15 | 四級化チューブリシン化合物の複合体 |
| JP2022084444A Division JP7559006B2 (ja) | 2015-12-04 | 2022-05-24 | 四級化チューブリシン化合物の複合体 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2019501131A JP2019501131A (ja) | 2019-01-17 |
| JP2019501131A5 true JP2019501131A5 (https=) | 2021-07-29 |
Family
ID=58798046
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018526574A Withdrawn JP2019501131A (ja) | 2015-12-04 | 2016-12-02 | 四級化チューブリシン化合物の複合体 |
| JP2021099570A Active JP7241811B2 (ja) | 2015-12-04 | 2021-06-15 | 四級化チューブリシン化合物の複合体 |
| JP2022084444A Active JP7559006B2 (ja) | 2015-12-04 | 2022-05-24 | 四級化チューブリシン化合物の複合体 |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021099570A Active JP7241811B2 (ja) | 2015-12-04 | 2021-06-15 | 四級化チューブリシン化合物の複合体 |
| JP2022084444A Active JP7559006B2 (ja) | 2015-12-04 | 2022-05-24 | 四級化チューブリシン化合物の複合体 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US11229708B2 (https=) |
| EP (2) | EP3383420B1 (https=) |
| JP (3) | JP2019501131A (https=) |
| KR (1) | KR20180090290A (https=) |
| CN (1) | CN108367043A (https=) |
| AU (1) | AU2016363013B2 (https=) |
| CA (1) | CA3006000A1 (https=) |
| ES (1) | ES2919323T3 (https=) |
| IL (2) | IL259478B (https=) |
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2016
- 2016-12-02 CN CN201680072182.0A patent/CN108367043A/zh active Pending
- 2016-12-02 CA CA3006000A patent/CA3006000A1/en active Pending
- 2016-12-02 EP EP16871672.8A patent/EP3383420B1/en active Active
- 2016-12-02 WO PCT/US2016/064834 patent/WO2017096311A1/en not_active Ceased
- 2016-12-02 JP JP2018526574A patent/JP2019501131A/ja not_active Withdrawn
- 2016-12-02 SG SG10202010590UA patent/SG10202010590UA/en unknown
- 2016-12-02 KR KR1020187017509A patent/KR20180090290A/ko not_active Withdrawn
- 2016-12-02 EP EP22162472.9A patent/EP4074328A1/en not_active Withdrawn
- 2016-12-02 AU AU2016363013A patent/AU2016363013B2/en active Active
- 2016-12-02 TW TW105140035A patent/TWI814699B/zh active
- 2016-12-02 SG SG11201804268RA patent/SG11201804268RA/en unknown
- 2016-12-02 MX MX2018006218A patent/MX2018006218A/es unknown
- 2016-12-02 TW TW112131161A patent/TWI852735B/zh active
- 2016-12-02 ES ES16871672T patent/ES2919323T3/es active Active
- 2016-12-02 US US15/781,244 patent/US11229708B2/en active Active
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2018
- 2018-05-18 MX MX2023002599A patent/MX2023002599A/es unknown
- 2018-05-21 IL IL259478A patent/IL259478B/en unknown
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2021
- 2021-06-15 JP JP2021099570A patent/JP7241811B2/ja active Active
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2022
- 2022-02-20 IL IL290733A patent/IL290733A/en unknown
- 2022-05-24 JP JP2022084444A patent/JP7559006B2/ja active Active
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