JP7032428B2 - Mcl-1阻害剤の合成 - Google Patents
Mcl-1阻害剤の合成 Download PDFInfo
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- JP7032428B2 JP7032428B2 JP2019552891A JP2019552891A JP7032428B2 JP 7032428 B2 JP7032428 B2 JP 7032428B2 JP 2019552891 A JP2019552891 A JP 2019552891A JP 2019552891 A JP2019552891 A JP 2019552891A JP 7032428 B2 JP7032428 B2 JP 7032428B2
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- methyl
- mol
- pyrazole
- solution
- dimethyl
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- 101001056180 Homo sapiens Induced myeloid leukemia cell differentiation protein Mcl-1 Proteins 0.000 title description 12
- 102100026539 Induced myeloid leukemia cell differentiation protein Mcl-1 Human genes 0.000 title description 12
- 230000015572 biosynthetic process Effects 0.000 title description 7
- 238000003786 synthesis reaction Methods 0.000 title description 7
- 239000003112 inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 158
- 239000000543 intermediate Substances 0.000 description 117
- -1 p-methoxybenzyl Chemical group 0.000 description 99
- 239000000243 solution Substances 0.000 description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 76
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 72
- 239000002904 solvent Substances 0.000 description 71
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 62
- 239000000203 mixture Substances 0.000 description 57
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 51
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 37
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 36
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 35
- 239000002002 slurry Substances 0.000 description 34
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 31
- 238000000034 method Methods 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
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- 239000003795 chemical substances by application Substances 0.000 description 20
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- 125000006239 protecting group Chemical group 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical group CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 13
- ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 13
- PRPINYUDVPFIRX-UHFFFAOYSA-N 1-naphthaleneacetic acid Chemical compound C1=CC=C2C(CC(=O)O)=CC=CC2=C1 PRPINYUDVPFIRX-UHFFFAOYSA-N 0.000 description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical group [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 239000002253 acid Substances 0.000 description 12
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 12
- 239000003638 chemical reducing agent Substances 0.000 description 12
- 229940125904 compound 1 Drugs 0.000 description 12
- 239000012065 filter cake Substances 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical group [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 description 11
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- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 10
- SCVJRXQHFJXZFZ-KVQBGUIXSA-N 2-amino-9-[(2r,4s,5r)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-3h-purine-6-thione Chemical compound C1=2NC(N)=NC(=S)C=2N=CN1[C@H]1C[C@H](O)[C@@H](CO)O1 SCVJRXQHFJXZFZ-KVQBGUIXSA-N 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 9
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical group [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 9
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical group CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 8
- 239000003929 acidic solution Substances 0.000 description 8
- 230000002378 acidificating effect Effects 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 239000012280 lithium aluminium hydride Substances 0.000 description 8
- 238000000634 powder X-ray diffraction Methods 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000000523 sample Substances 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
- 239000003643 water by type Substances 0.000 description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 7
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical group BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 238000000113 differential scanning calorimetry Methods 0.000 description 7
- 239000000706 filtrate Substances 0.000 description 7
- 229910052739 hydrogen Chemical group 0.000 description 7
- 239000001257 hydrogen Chemical group 0.000 description 7
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 7
- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- KJCVRFUGPWSIIH-UHFFFAOYSA-N 1-naphthol Chemical compound C1=CC=C2C(O)=CC=CC2=C1 KJCVRFUGPWSIIH-UHFFFAOYSA-N 0.000 description 6
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 239000012346 acetyl chloride Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000012022 methylating agents Substances 0.000 description 6
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- 239000002243 precursor Substances 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- 238000002411 thermogravimetry Methods 0.000 description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 5
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 description 5
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- 238000006243 chemical reaction Methods 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
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- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 5
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- RHTVZWCYCZFACI-UHFFFAOYSA-N methyl 5-(chloromethyl)-1-methylpyrazole-3-carboxylate Chemical compound ClCC1=CC(=NN1C)C(=O)OC RHTVZWCYCZFACI-UHFFFAOYSA-N 0.000 description 5
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- 238000005406 washing Methods 0.000 description 5
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- TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 4
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- 206010035226 Plasma cell myeloma Diseases 0.000 description 4
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- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- PZBBESSUKAHBHD-UHFFFAOYSA-N methyl 2-oxocyclopentane-1-carboxylate Chemical compound COC(=O)C1CCCC1=O PZBBESSUKAHBHD-UHFFFAOYSA-N 0.000 description 4
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- XMBWDFGMSWQBCA-UHFFFAOYSA-M iodide Chemical compound [I-] XMBWDFGMSWQBCA-UHFFFAOYSA-M 0.000 description 3
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- 239000000126 substance Substances 0.000 description 3
- 125000003944 tolyl group Chemical group 0.000 description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 3
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- XJBMHIHXRARJJS-UHFFFAOYSA-N (1,5-dimethylpyrazol-3-yl)methanol Chemical compound CC1=CC(CO)=NN1C XJBMHIHXRARJJS-UHFFFAOYSA-N 0.000 description 2
- HFXVLGOYQIKRTO-FYZOBXCZSA-N (1r)-1-(2-nitrophenyl)ethanamine;hydrochloride Chemical compound Cl.C[C@@H](N)C1=CC=CC=C1[N+]([O-])=O HFXVLGOYQIKRTO-FYZOBXCZSA-N 0.000 description 2
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 description 2
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- C07C245/00—Compounds containing chains of at least two nitrogen atoms with at least one nitrogen-to-nitrogen multiple bond
- C07C245/02—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides
- C07C245/06—Azo compounds, i.e. compounds having the free valencies of —N=N— groups attached to different atoms, e.g. diazohydroxides with nitrogen atoms of azo groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
- C07C251/72—Hydrazones
- C07C251/74—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C251/76—Hydrazones having doubly-bound carbon atoms of hydrazone groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of a saturated carbon skeleton
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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| US11691989B2 (en) | 2018-11-22 | 2023-07-04 | Ascentage Pharma (Suzhou) Co., Ltd. | Macrocyclic indoles as Mcl-1 inhibitors |
| US12319703B2 (en) | 2019-01-23 | 2025-06-03 | Ascentage Pharma (Suzhou) Co., Ltd. | Macrocyclic fused pyrazoles as Mcl-1 inhibitors |
| KR20220024694A (ko) | 2019-06-21 | 2022-03-03 | 얀센 파마슈티카 엔.브이. | Mcl-1의 거대환식 억제제 |
| WO2021005043A1 (en) | 2019-07-09 | 2021-01-14 | Janssen Pharmaceutica Nv | Macrocyclic spirocycle derivatives as mcl-1 inhibitors |
| WO2021092053A1 (en) * | 2019-11-08 | 2021-05-14 | Unity Biotechnology, Inc. | Mcl-1 inhibitor macrocycle compounds for use in clinical management of conditions caused or mediated by senescent cells and for treating cancer |
| WO2021099579A1 (en) | 2019-11-21 | 2021-05-27 | Janssen Pharmaceutica Nv | Macrocyclic indole derivatives as mcl-1 inhibitors |
| MX2022006180A (es) | 2019-11-21 | 2022-06-14 | Janssen Pharmaceutica Nv | Derivados macrociclicos de sulfonilo como inhibidores de mcl-1. |
| JP2023514364A (ja) | 2020-02-21 | 2023-04-05 | ヤンセン ファーマシューティカ エヌ.ベー. | Mcl-1の阻害剤としての大環状インドール誘導体 |
| EP4157852A1 (en) | 2020-05-29 | 2023-04-05 | JANSSEN Pharmaceutica NV | Macrocyclic 7-pyrazol-5-yl-indole derivatives as inhibitors of mcl-1 |
| MX2022015998A (es) * | 2020-06-19 | 2023-04-12 | Janssen Pharmaceutica Nv | Derivados de 4-(pirazol-5-il)-indol macrocíclico unidos a n como inhibidores de mcl-1. |
| WO2021255257A1 (en) | 2020-06-19 | 2021-12-23 | Janssen Pharmaceutica Nv | N-linked macrocyclic 7-(pyrazol-5-yl)-indole derivatives as inhibitors of mcl-1 |
| CA3184877A1 (en) | 2020-07-08 | 2022-01-13 | Benoit Christian Albert Ghislain De Boeck | Macrocyclic ether containing indole derivatives as inhibitors of mcl-1 |
| WO2022032284A1 (en) * | 2020-08-07 | 2022-02-10 | Zeno Management, Inc. | Macrocyclic compounds |
| JP2023553719A (ja) | 2020-12-17 | 2023-12-25 | ヤンセン ファーマシューティカ エヌ.ベー. | Mcl-1阻害剤としての分岐大環状4-(ピラゾール-5-イル)-インドール誘導体 |
| JP2024506648A (ja) | 2021-02-12 | 2024-02-14 | ヤンセン ファーマシューティカ エヌ.ベー. | がんの治療のためのmcl-1阻害剤としての大環状1,3-架橋6-クロロ-7-ピラゾール-4-イル-1h-インドール-2-カルボキシレート及び6-クロロ-7-ピリミジン-5-イル-1h-インドール-2-カルボキシレート誘導体 |
| US11931424B2 (en) | 2021-06-11 | 2024-03-19 | Gilead Sciences, Inc. | Combination MCL-1 inhibitors with anti-body drug conjugates |
| WO2022261301A1 (en) | 2021-06-11 | 2022-12-15 | Gilead Sciences, Inc. | Combination mcl-1 inhibitors with anti-cancer agents |
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| EP2915811A1 (en) * | 2014-03-04 | 2015-09-09 | Centre Régional de Lutte contre le Cancer - Centre François Baclesse | MCL-1 modulating compounds for cancer treatment |
| CN105061315B (zh) * | 2015-08-06 | 2017-10-24 | 大连理工大学 | 一类1,5‑二苯基吡唑‑3‑羧酸类化合物及其应用 |
| MX386103B (es) * | 2016-04-22 | 2025-03-18 | Astrazeneca Ab | Inhibidores de mcl-1 y metodos de uso de los mismos. |
| CN106478606B (zh) * | 2016-09-21 | 2019-05-10 | 沈阳药科大学 | N-取代吲哚类衍生物及其应用 |
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| CO2019010035A2 (es) | 2019-09-30 |
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| MX2019011468A (es) | 2019-11-01 |
| AU2018244180A1 (en) | 2019-11-07 |
| TW201902868A (zh) | 2019-01-16 |
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| CN110536884A (zh) | 2019-12-03 |
| TWI781996B (zh) | 2022-11-01 |
| AR111304A1 (es) | 2019-06-26 |
| EP3601230A1 (en) | 2020-02-05 |
| EP3601230B1 (en) | 2022-01-26 |
| EA038226B1 (ru) | 2021-07-27 |
| JP2020515557A (ja) | 2020-05-28 |
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| CN110536884B (zh) | 2023-05-02 |
| WO2018178227A1 (en) | 2018-10-04 |
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| MX387814B (es) | 2025-03-04 |
| US11149024B2 (en) | 2021-10-19 |
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