JP7631348B2 - 組み合わせ - Google Patents
組み合わせ Download PDFInfo
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- JP7631348B2 JP7631348B2 JP2022538220A JP2022538220A JP7631348B2 JP 7631348 B2 JP7631348 B2 JP 7631348B2 JP 2022538220 A JP2022538220 A JP 2022538220A JP 2022538220 A JP2022538220 A JP 2022538220A JP 7631348 B2 JP7631348 B2 JP 7631348B2
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- Prior art keywords
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- 150000001875 compounds Chemical class 0.000 claims description 236
- 125000000217 alkyl group Chemical group 0.000 claims description 208
- 150000003839 salts Chemical class 0.000 claims description 124
- -1 hydroxy, amino Chemical group 0.000 claims description 102
- 125000000623 heterocyclic group Chemical group 0.000 claims description 98
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 82
- 125000004429 atom Chemical group 0.000 claims description 69
- 229910052736 halogen Inorganic materials 0.000 claims description 55
- 150000002367 halogens Chemical class 0.000 claims description 55
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 48
- 125000001424 substituent group Chemical group 0.000 claims description 45
- 206010028980 Neoplasm Diseases 0.000 claims description 36
- 125000003277 amino group Chemical class 0.000 claims description 34
- 201000010099 disease Diseases 0.000 claims description 33
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 33
- 150000001412 amines Chemical class 0.000 claims description 31
- 239000000203 mixture Substances 0.000 claims description 29
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 238000000034 method Methods 0.000 claims description 21
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 20
- 125000001153 fluoro group Chemical group F* 0.000 claims description 18
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 18
- 125000002252 acyl group Chemical group 0.000 claims description 14
- 125000002924 primary amino group Chemical class [H]N([H])* 0.000 claims description 14
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 10
- 208000002250 Hematologic Neoplasms Diseases 0.000 claims description 8
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 8
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 8
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- 125000001309 chloro group Chemical group Cl* 0.000 claims description 7
- 125000006714 (C3-C10) heterocyclyl group Chemical group 0.000 claims description 6
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- 101100490437 Mus musculus Acvrl1 gene Proteins 0.000 claims description 4
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- 208000002471 Penile Neoplasms Diseases 0.000 claims description 2
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- 210000000232 gallbladder Anatomy 0.000 claims description 2
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- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 2
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 2
- 210000000244 kidney pelvis Anatomy 0.000 claims description 2
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 claims description 2
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- 208000020816 lung neoplasm Diseases 0.000 claims description 2
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- 201000002510 thyroid cancer Diseases 0.000 claims description 2
- 201000011294 ureter cancer Diseases 0.000 claims description 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims description 2
- 206010046766 uterine cancer Diseases 0.000 claims description 2
- 239000008177 pharmaceutical agent Substances 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 description 98
- 125000001072 heteroaryl group Chemical group 0.000 description 84
- 125000004432 carbon atom Chemical group C* 0.000 description 76
- 125000002950 monocyclic group Chemical group 0.000 description 59
- 125000005842 heteroatom Chemical group 0.000 description 52
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 38
- 125000000392 cycloalkenyl group Chemical group 0.000 description 37
- 125000003342 alkenyl group Chemical group 0.000 description 34
- 125000000304 alkynyl group Chemical group 0.000 description 34
- 150000002431 hydrogen Chemical class 0.000 description 33
- 125000002947 alkylene group Chemical group 0.000 description 27
- 229910052757 nitrogen Inorganic materials 0.000 description 23
- 229910052799 carbon Inorganic materials 0.000 description 19
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 18
- 125000004452 carbocyclyl group Chemical group 0.000 description 17
- 125000002619 bicyclic group Chemical group 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 14
- 210000004027 cell Anatomy 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 125000003003 spiro group Chemical group 0.000 description 13
- 238000011282 treatment Methods 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
- 125000003545 alkoxy group Chemical group 0.000 description 12
- 125000004122 cyclic group Chemical group 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 10
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 125000001188 haloalkyl group Chemical group 0.000 description 10
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 10
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- 125000003367 polycyclic group Chemical group 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 description 8
- 230000008901 benefit Effects 0.000 description 8
- XSCHRSMBECNVNS-UHFFFAOYSA-N benzopyrazine Natural products N1=CC=NC2=CC=CC=C21 XSCHRSMBECNVNS-UHFFFAOYSA-N 0.000 description 8
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 8
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- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 8
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 8
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 7
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 7
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- 150000001721 carbon Chemical group 0.000 description 7
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 7
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- LBUJPTNKIBCYBY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline Chemical compound C1=CC=C2CCCNC2=C1 LBUJPTNKIBCYBY-UHFFFAOYSA-N 0.000 description 6
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- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/63—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide
- A61K31/635—Compounds containing para-N-benzenesulfonyl-N-groups, e.g. sulfanilamide, p-nitrobenzenesulfonyl hydrazide having a heterocyclic ring, e.g. sulfadiazine
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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| AU2020384291A1 (en) | 2019-11-15 | 2022-05-26 | Recurium Ip Holdings, Llc | Chiral synthesis of a tertiary alcohol |
| WO2022011391A1 (en) | 2020-07-09 | 2022-01-13 | Recurium Ip Holdings, Llc | Salts and forms of a wee1 inhibitor |
| EP4431511A4 (en) * | 2021-11-09 | 2025-10-15 | Hangzhou Glubio Pharmaceutical Co Ltd | WEE1 PROTEIN KINASE DEGRADING AGENT AND ITS USE |
| WO2023114877A1 (en) * | 2021-12-15 | 2023-06-22 | Recurium Ip Holdings, Llc | Triple therapy combinations of bcl-2 inhibitors, wee-1 inhibitors and other chemotherapeutic agents |
| WO2025193930A1 (en) * | 2024-03-14 | 2025-09-18 | Zeno Management, Inc. | Wee1 inhibitor combination therapy |
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| WO2019139899A1 (en) | 2018-01-10 | 2019-07-18 | Zeno Royalties & Milestones, LLC | Benzamide compounds |
| WO2019173082A1 (en) | 2018-03-09 | 2019-09-12 | Zeno Royalties & Milestones, LLC | Substituted l,2-dihydro-3h-pyrazolo[3,4-d]pyrimidin-3-ones |
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| MX2020001235A (es) * | 2017-08-01 | 2020-07-20 | Recurium Ip Holdings Llc | Análogos de 1,2-dihidro-3h-pirazolo[3,4-d]pirimidin-3-ona. |
| CN109422754A (zh) * | 2017-08-24 | 2019-03-05 | 上海迪诺医药科技有限公司 | 吡唑并[3,4-d]嘧啶-3-酮衍生物、其药物组合物及应用 |
| EP3694861A4 (en) * | 2017-10-09 | 2021-05-19 | Nuvation Bio Inc. | HETEROCYCLIC COMPOUNDS AND USES THEREOF |
| WO2023114877A1 (en) * | 2021-12-15 | 2023-06-22 | Recurium Ip Holdings, Llc | Triple therapy combinations of bcl-2 inhibitors, wee-1 inhibitors and other chemotherapeutic agents |
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| WO2019139899A1 (en) | 2018-01-10 | 2019-07-18 | Zeno Royalties & Milestones, LLC | Benzamide compounds |
| WO2019173082A1 (en) | 2018-03-09 | 2019-09-12 | Zeno Royalties & Milestones, LLC | Substituted l,2-dihydro-3h-pyrazolo[3,4-d]pyrimidin-3-ones |
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