JP2018527292A5 - - Google Patents
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- JP2018527292A5 JP2018527292A5 JP2017565192A JP2017565192A JP2018527292A5 JP 2018527292 A5 JP2018527292 A5 JP 2018527292A5 JP 2017565192 A JP2017565192 A JP 2017565192A JP 2017565192 A JP2017565192 A JP 2017565192A JP 2018527292 A5 JP2018527292 A5 JP 2018527292A5
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- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims description 135
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- 150000003839 salts Chemical class 0.000 claims description 57
- 239000012453 solvate Substances 0.000 claims description 38
- 239000003814 drug Substances 0.000 claims description 33
- 125000004432 carbon atom Chemical group C* 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 32
- 150000002367 halogens Chemical class 0.000 claims description 32
- 125000006850 spacer group Chemical group 0.000 claims description 32
- 229940079593 drug Drugs 0.000 claims description 29
- -1 apoptosis modulator Substances 0.000 claims description 24
- 125000001072 heteroaryl group Chemical group 0.000 claims description 24
- 125000003107 substituted aryl group Chemical group 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 14
- 125000006575 electron-withdrawing group Chemical group 0.000 claims description 14
- 239000012634 fragment Substances 0.000 claims description 14
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 229940124599 anti-inflammatory drug Drugs 0.000 claims description 12
- 125000001188 haloalkyl group Chemical group 0.000 claims description 12
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims description 10
- 229910021645 metal ion Inorganic materials 0.000 claims description 10
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 10
- 230000003612 virological effect Effects 0.000 claims description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin 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-TZSSRYMLSA-N 0.000 claims description 8
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 claims description 8
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 claims description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 8
- 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 description 8
- 125000002252 acyl group Chemical group 0.000 claims description 8
- 229940045799 anthracyclines and related substance Drugs 0.000 claims description 8
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- 125000005439 maleimidyl group Chemical group C1(C=CC(N1*)=O)=O 0.000 claims description 8
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 8
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 8
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- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 6
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- 229910001413 alkali metal ion Inorganic materials 0.000 claims description 6
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- 125000002228 disulfide group Chemical group 0.000 claims description 6
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 6
- ZBKFYXZXZJPWNQ-UHFFFAOYSA-N isothiocyanate group Chemical group [N-]=C=S ZBKFYXZXZJPWNQ-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- NMHMNPHRMNGLLB-UHFFFAOYSA-N phloretic acid Chemical group OC(=O)CCC1=CC=C(O)C=C1 NMHMNPHRMNGLLB-UHFFFAOYSA-N 0.000 claims description 6
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 108090000623 proteins and genes Proteins 0.000 claims description 6
- 125000005030 pyridylthio group Chemical group N1=C(C=CC=C1)S* 0.000 claims description 6
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims description 4
- SLURUCSFDHKXFR-WWMWMSKMSA-N (7s,9s)-7-[[(1s,3r,4as,9s,9ar,10as)-9-methoxy-1-methyl-3,4,4a,6,7,9,9a,10a-octahydro-1h-pyrano[1,2][1,3]oxazolo[3,4-b][1,4]oxazin-3-yl]oxy]-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O=C1C2=CC=CC(OC)=C2C(=O)C(C(O)=C23)=C1C(O)=C3C[C@@](O)(C(=O)CO)C[C@@H]2O[C@H]1C[C@@H]2N3CCO[C@H](OC)[C@H]3O[C@@H]2[C@H](C)O1 SLURUCSFDHKXFR-WWMWMSKMSA-N 0.000 claims description 4
- FPVKHBSQESCIEP-UHFFFAOYSA-N (8S)-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ol Natural products C1C(O)C(CO)OC1N1C(NC=NCC2O)=C2N=C1 FPVKHBSQESCIEP-UHFFFAOYSA-N 0.000 claims description 4
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 claims description 4
- ZZVDXRCAGGQFAK-UHFFFAOYSA-N 2h-oxazaphosphinine Chemical compound N1OC=CC=P1 ZZVDXRCAGGQFAK-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 4
- 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 description 4
- 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 description 4
- FJHBVJOVLFPMQE-QFIPXVFZSA-N 7-Ethyl-10-Hydroxy-Camptothecin Chemical compound C1=C(O)C=C2C(CC)=C(CN3C(C4=C([C@@](C(=O)OC4)(O)CC)C=C33)=O)C3=NC2=C1 FJHBVJOVLFPMQE-QFIPXVFZSA-N 0.000 claims description 4
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 claims description 4
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- 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 description 4
- 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 description 4
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- 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 description 4
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| JP2019513829A (ja) * | 2016-04-11 | 2019-05-30 | ３アール ヴァロ、エス．イー．シー． | 抗炎症剤、抗転移剤及び／又は抗癌剤として使用するためのアミノ安息香酸誘導体 |
| US10111966B2 (en) | 2016-06-17 | 2018-10-30 | Magenta Therapeutics, Inc. | Methods for the depletion of CD117+ cells |
| US10576161B2 (en) | 2017-01-20 | 2020-03-03 | Magenta Therapeutics, Inc. | Compositions and methods for the depletion of CD137+ cells |
| EP3617221A4 (en) * | 2017-04-19 | 2021-04-14 | Sichuan Kelun-Biotech Biopharmaceutical Co., Ltd. | CYTOTOXIN AND CONJUGATE, USES THEREOF AND MANUFACTURING PROCESSES THEREFORE |
| JP7062754B2 (ja) | 2017-08-15 | 2022-05-06 | ナントセル，インコーポレイテッド | ｈａＮＫセツキシマブ併用及び方法 |
| EP3717018A1 (en) * | 2017-11-30 | 2020-10-07 | Centurion BioPharma Corporation | Maytansinoid-based drug delivery systems |
| AU2018375787B2 (en) * | 2017-11-30 | 2023-02-23 | Ladrx Corporation | Albumin-binding prodrugs of auristatin E derivatives |
| CN119241554A (zh) | 2017-12-15 | 2025-01-03 | 四川科伦博泰生物医药股份有限公司 | 生物活性物偶联物及其制备方法和用途 |
| CN110090308B (zh) * | 2018-01-30 | 2023-03-24 | 四川科伦博泰生物医药股份有限公司 | 制备偶联物的方法 |
| CN110227164B (zh) * | 2018-03-06 | 2021-11-23 | 江苏吉贝尔药业股份有限公司 | 含酮羰基的疏水性抗肿瘤药物及其缀合物、含有缀合物的纳米制剂及其制备方法及应用 |
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| US4816567A (en) | 1983-04-08 | 1989-03-28 | Genentech, Inc. | Recombinant immunoglobin preparations |
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| US4699880A (en) | 1984-09-25 | 1987-10-13 | Immunomedics, Inc. | Method of producing monoclonal anti-idiotype antibody |
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| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| US4946778A (en) | 1987-09-21 | 1990-08-07 | Genex Corporation | Single polypeptide chain binding molecules |
| DE3853515T3 (de) | 1987-05-21 | 2005-08-25 | Micromet Ag | Multifunktionelle proteine mit vorbestimmter zielsetzung. |
| US4966999A (en) * | 1988-06-07 | 1990-10-30 | Cytogen Corporation | Radiohalogenated compounds for site specific labeling |
| IL162181A (en) | 1988-12-28 | 2006-04-10 | Pdl Biopharma Inc | A method of producing humanized immunoglubulin, and polynucleotides encoding the same |
| DE69233482T2 (de) | 1991-05-17 | 2006-01-12 | Merck & Co., Inc. | Verfahren zur Verminderung der Immunogenität der variablen Antikörperdomänen |
| JP3540315B2 (ja) | 1991-09-23 | 2004-07-07 | メディカル リサーチ カウンシル | キメラ抗体の製造−組合せアプローチ |
| DE614989T1 (de) | 1993-02-17 | 1995-09-28 | Morphosys Proteinoptimierung | Verfahren für in vivo Selektion von Ligandenbindende Proteine. |
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| US6884869B2 (en) | 2001-04-30 | 2005-04-26 | Seattle Genetics, Inc. | Pentapeptide compounds and uses related thereto |
| NZ547370A (en) | 2003-12-04 | 2010-09-30 | Amr Technology Inc | Vinca derivatives |
| MX2009012370A (es) * | 2007-05-16 | 2010-04-22 | Ktb Tumorforschungs Gmbh | Formulacion de antraciclina de baja viscosidad. |
| EP2289558A1 (en) | 2009-08-25 | 2011-03-02 | KTB Tumorforschungsgesellschaft mbH | Bisphosphonate-prodrugs |
| EP2630971B8 (en) * | 2012-02-21 | 2017-12-13 | Vergell Medical S.A. | Combinations of albumin-based drug delivery systems |
| US20140221429A1 (en) * | 2013-02-04 | 2014-08-07 | Saud Ibrahim Al-Resayes | Heterocyclic schiff's bases as novel and new antiglycation agents |
| CA2987091A1 (en) | 2015-06-15 | 2016-12-22 | Abbott Diabetes Care Inc. | Stabilized lactate responsive enzymes, electrodes and sensors, and methods for making and using the same |
| EP3717018A1 (en) | 2017-11-30 | 2020-10-07 | Centurion BioPharma Corporation | Maytansinoid-based drug delivery systems |
| AU2018375787B2 (en) | 2017-11-30 | 2023-02-23 | Ladrx Corporation | Albumin-binding prodrugs of auristatin E derivatives |
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