JPWO2021021761A5 - - Google Patents
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- JPWO2021021761A5 JPWO2021021761A5 JP2022506188A JP2022506188A JPWO2021021761A5 JP WO2021021761 A5 JPWO2021021761 A5 JP WO2021021761A5 JP 2022506188 A JP2022506188 A JP 2022506188A JP 2022506188 A JP2022506188 A JP 2022506188A JP WO2021021761 A5 JPWO2021021761 A5 JP WO2021021761A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- haloalkyl
- heterocyclyl
- cells
- tautomer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
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- 150000001875 compounds Chemical class 0.000 claims 45
- 229910052739 hydrogen Inorganic materials 0.000 claims 45
- 239000001257 hydrogen Substances 0.000 claims 45
- 150000003839 salts Chemical class 0.000 claims 37
- 125000000623 heterocyclic group Chemical group 0.000 claims 31
- 210000002865 immune cell Anatomy 0.000 claims 30
- 150000002431 hydrogen Chemical class 0.000 claims 27
- 229910052757 nitrogen Inorganic materials 0.000 claims 21
- 206010028980 Neoplasm Diseases 0.000 claims 19
- 125000005843 halogen group Chemical group 0.000 claims 18
- 239000000203 mixture Substances 0.000 claims 18
- 210000003171 tumor-infiltrating lymphocyte Anatomy 0.000 claims 18
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 16
- 201000011510 cancer Diseases 0.000 claims 16
- 229910052799 carbon Inorganic materials 0.000 claims 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 15
- 229940122650 Cbl-b inhibitor Drugs 0.000 claims 14
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 14
- 125000004432 carbon atom Chemical group C* 0.000 claims 14
- 210000004027 cell Anatomy 0.000 claims 14
- 229910052717 sulfur Inorganic materials 0.000 claims 14
- 239000011593 sulfur Substances 0.000 claims 14
- 125000003118 aryl group Chemical group 0.000 claims 12
- 125000004093 cyano group Chemical group *C#N 0.000 claims 12
- 230000000694 effects Effects 0.000 claims 12
- 238000000034 method Methods 0.000 claims 12
- 239000003814 drug Substances 0.000 claims 11
- 125000001072 heteroaryl group Chemical group 0.000 claims 11
- 125000002950 monocyclic group Chemical group 0.000 claims 11
- 229940034982 antineoplastic agent Drugs 0.000 claims 10
- 239000002246 antineoplastic agent Substances 0.000 claims 10
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims 10
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 10
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 9
- 125000004043 oxo group Chemical group O=* 0.000 claims 9
- -1 C 1 -C 6 alkyl-OH Chemical group 0.000 claims 8
- 238000004519 manufacturing process Methods 0.000 claims 8
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims 7
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims 7
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims 7
- 102000000588 Interleukin-2 Human genes 0.000 claims 7
- 108010002350 Interleukin-2 Proteins 0.000 claims 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims 7
- 125000001153 fluoro group Chemical group F* 0.000 claims 7
- 125000005842 heteroatom Chemical group 0.000 claims 7
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims 7
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 7
- 229910052760 oxygen Chemical group 0.000 claims 7
- 239000001301 oxygen Chemical group 0.000 claims 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 6
- 102100035273 E3 ubiquitin-protein ligase CBL-B Human genes 0.000 claims 6
- 101000737265 Homo sapiens E3 ubiquitin-protein ligase CBL-B Proteins 0.000 claims 6
- 210000001744 T-lymphocyte Anatomy 0.000 claims 6
- 238000012258 culturing Methods 0.000 claims 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims 6
- 201000010099 disease Diseases 0.000 claims 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 6
- 102000037982 Immune checkpoint proteins Human genes 0.000 claims 5
- 108091008036 Immune checkpoint proteins Proteins 0.000 claims 5
- 230000006044 T cell activation Effects 0.000 claims 5
- 239000006143 cell culture medium Substances 0.000 claims 5
- 201000005787 hematologic cancer Diseases 0.000 claims 5
- 229940124597 therapeutic agent Drugs 0.000 claims 5
- 102000004127 Cytokines Human genes 0.000 claims 4
- 108090000695 Cytokines Proteins 0.000 claims 4
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 claims 4
- 230000000340 anti-metabolite Effects 0.000 claims 4
- 229940100197 antimetabolite Drugs 0.000 claims 4
- 239000002256 antimetabolite Substances 0.000 claims 4
- 108700010039 chimeric receptor Proteins 0.000 claims 4
- 210000000822 natural killer cell Anatomy 0.000 claims 4
- 238000001959 radiotherapy Methods 0.000 claims 4
- 108010074708 B7-H1 Antigen Proteins 0.000 claims 3
- 108010021064 CTLA-4 Antigen Proteins 0.000 claims 3
- 229940045513 CTLA4 antagonist Drugs 0.000 claims 3
- 241000196324 Embryophyta Species 0.000 claims 3
- 102100024216 Programmed cell death 1 ligand 1 Human genes 0.000 claims 3
- 229930013930 alkaloid Natural products 0.000 claims 3
- 229940100198 alkylating agent Drugs 0.000 claims 3
- 239000002168 alkylating agent Substances 0.000 claims 3
- 210000003719 b-lymphocyte Anatomy 0.000 claims 3
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- 239000012634 fragment Substances 0.000 claims 3
- 238000007911 parenteral administration Methods 0.000 claims 3
- 150000003058 platinum compounds Chemical class 0.000 claims 3
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims 2
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 2
- 230000003844 B-cell-activation Effects 0.000 claims 2
- 201000009030 Carcinoma Diseases 0.000 claims 2
- 108010019670 Chimeric Antigen Receptors Proteins 0.000 claims 2
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- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims 2
- 101000934374 Homo sapiens Early activation antigen CD69 Proteins 0.000 claims 2
- 101001023712 Homo sapiens Nectin-3 Proteins 0.000 claims 2
- 102100037850 Interferon gamma Human genes 0.000 claims 2
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- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 claims 2
- 150000003797 alkaloid derivatives Chemical class 0.000 claims 2
- 125000000217 alkyl group Chemical group 0.000 claims 2
- 125000002947 alkylene group Chemical group 0.000 claims 2
- 239000005557 antagonist Substances 0.000 claims 2
- 125000002619 bicyclic group Chemical group 0.000 claims 2
- 230000003115 biocidal effect Effects 0.000 claims 2
- 239000012472 biological sample Substances 0.000 claims 2
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- 239000008280 blood Substances 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 2
- 125000004122 cyclic group Chemical group 0.000 claims 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 2
- 231100000433 cytotoxic Toxicity 0.000 claims 2
- 230000001472 cytotoxic effect Effects 0.000 claims 2
- 230000003247 decreasing effect Effects 0.000 claims 2
- 229960002949 fluorouracil Drugs 0.000 claims 2
- 125000001188 haloalkyl group Chemical group 0.000 claims 2
- 210000003958 hematopoietic stem cell Anatomy 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 210000003738 lymphoid progenitor cell Anatomy 0.000 claims 2
- 201000001441 melanoma Diseases 0.000 claims 2
- 210000003643 myeloid progenitor cell Anatomy 0.000 claims 2
- 229960003552 other antineoplastic agent in atc Drugs 0.000 claims 2
- 229960001592 paclitaxel Drugs 0.000 claims 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 2
- 210000001778 pluripotent stem cell Anatomy 0.000 claims 2
- 210000001948 pro-b lymphocyte Anatomy 0.000 claims 2
- 210000001978 pro-t lymphocyte Anatomy 0.000 claims 2
- 239000003909 protein kinase inhibitor Substances 0.000 claims 2
- 239000000523 sample Substances 0.000 claims 2
- 125000003003 spiro group Chemical group 0.000 claims 2
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims 2
- 229960001674 tegafur Drugs 0.000 claims 2
- WFWLQNSHRPWKFK-ZCFIWIBFSA-N tegafur Chemical compound O=C1NC(=O)C(F)=CN1[C@@H]1OCCC1 WFWLQNSHRPWKFK-ZCFIWIBFSA-N 0.000 claims 2
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims 2
- NNJPGOLRFBJNIW-HNNXBMFYSA-N (-)-demecolcine Chemical compound C1=C(OC)C(=O)C=C2[C@@H](NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-HNNXBMFYSA-N 0.000 claims 1
- FDKXTQMXEQVLRF-ZHACJKMWSA-N (E)-dacarbazine Chemical group CN(C)\N=N\c1[nH]cnc1C(N)=O FDKXTQMXEQVLRF-ZHACJKMWSA-N 0.000 claims 1
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 claims 1
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 claims 1
- IDPUKCWIGUEADI-UHFFFAOYSA-N 5-[bis(2-chloroethyl)amino]uracil Chemical compound ClCCN(CCCl)C1=CNC(=O)NC1=O IDPUKCWIGUEADI-UHFFFAOYSA-N 0.000 claims 1
- XAUDJQYHKZQPEU-KVQBGUIXSA-N 5-aza-2'-deoxycytidine Chemical compound O=C1N=C(N)N=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 XAUDJQYHKZQPEU-KVQBGUIXSA-N 0.000 claims 1
- NMUSYJAQQFHJEW-KVTDHHQDSA-N 5-azacytidine Chemical compound O=C1N=C(N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 NMUSYJAQQFHJEW-KVTDHHQDSA-N 0.000 claims 1
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims 1
- 108010006654 Bleomycin Proteins 0.000 claims 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims 1
- FVLVBPDQNARYJU-XAHDHGMMSA-N C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O Chemical compound C[C@H]1CCC(CC1)NC(=O)N(CCCl)N=O FVLVBPDQNARYJU-XAHDHGMMSA-N 0.000 claims 1
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims 1
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims 1
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- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 claims 1
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims 1
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- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims 1
- 108010092160 Dactinomycin Proteins 0.000 claims 1
- NNJPGOLRFBJNIW-UHFFFAOYSA-N Demecolcine Natural products C1=C(OC)C(=O)C=C2C(NC)CCC3=CC(OC)=C(OC)C(OC)=C3C2=C1 NNJPGOLRFBJNIW-UHFFFAOYSA-N 0.000 claims 1
- XXPXYPLPSDPERN-UHFFFAOYSA-N Ecteinascidin 743 Natural products COc1cc2C(NCCc2cc1O)C(=O)OCC3N4C(O)C5Cc6cc(C)c(OC)c(O)c6C(C4C(S)c7c(OC(=O)C)c(C)c8OCOc8c37)N5C XXPXYPLPSDPERN-UHFFFAOYSA-N 0.000 claims 1
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 claims 1
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- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 claims 1
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- 101000666896 Homo sapiens V-type immunoglobulin domain-containing suppressor of T-cell activation Proteins 0.000 claims 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims 1
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- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims 1
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- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims 1
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| WO2022272248A1 (en) * | 2021-06-21 | 2022-12-29 | Nimbus Clio, Inc. | Cbl-b modulators and uses thereof |
| CN113577265B (zh) * | 2021-08-04 | 2022-04-15 | 明济生物制药（北京）有限公司 | Til细胞及其制备方法以及在癌症治疗中的用途 |
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-
2020
- 2020-07-27 WO PCT/US2020/043788 patent/WO2021021761A1/en not_active Ceased
- 2020-07-27 CN CN202080068222.0A patent/CN114450271B/zh active Active
- 2020-07-27 MX MX2022001199A patent/MX2022001199A/es unknown
- 2020-07-27 JP JP2022506188A patent/JP7605824B2/ja active Active
- 2020-07-27 US US17/631,886 patent/US20220387395A1/en active Pending
- 2020-07-27 CA CA3148769A patent/CA3148769A1/en active Pending
- 2020-07-27 EP EP20757062.3A patent/EP4003965A1/en active Pending
- 2020-07-27 AU AU2020320195A patent/AU2020320195A1/en not_active Abandoned
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