JPWO2021163633A5 - - Google Patents
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- JPWO2021163633A5 JPWO2021163633A5 JP2022549152A JP2022549152A JPWO2021163633A5 JP WO2021163633 A5 JPWO2021163633 A5 JP WO2021163633A5 JP 2022549152 A JP2022549152 A JP 2022549152A JP 2022549152 A JP2022549152 A JP 2022549152A JP WO2021163633 A5 JPWO2021163633 A5 JP WO2021163633A5
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- pharmaceutical composition
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- alkyl
- inhibitor
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- 125000000547 substituted alkyl group Chemical group 0.000 claims description 36
- 239000003112 inhibitor Substances 0.000 claims description 28
- 125000003107 substituted aryl group Chemical group 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 229940124597 therapeutic agent Drugs 0.000 claims description 23
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 19
- 201000011510 cancer Diseases 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000004122 cyclic group Chemical group 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 125000001475 halogen functional group Chemical group 0.000 claims description 10
- 125000005553 heteroaryloxy group Chemical group 0.000 claims description 10
- 125000000623 heterocyclic group Chemical group 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 10
- 150000003573 thiols Chemical class 0.000 claims description 10
- 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 8
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 claims description 8
- 190000008236 carboplatin Chemical compound 0.000 claims description 8
- 229960001433 erlotinib Drugs 0.000 claims description 8
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 8
- SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 8
- 229960005277 gemcitabine Drugs 0.000 claims description 8
- 206010006187 Breast cancer Diseases 0.000 claims description 7
- 208000026310 Breast neoplasm Diseases 0.000 claims description 7
- 102100020689 Autophagy-related protein 13 Human genes 0.000 claims description 6
- 101000785138 Homo sapiens Autophagy-related protein 13 Proteins 0.000 claims description 6
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 125000001188 haloalkyl group Chemical group 0.000 claims description 6
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 6
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
- 201000002528 pancreatic cancer Diseases 0.000 claims description 6
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 6
- 108010012934 Albumin-Bound Paclitaxel Proteins 0.000 claims description 4
- BFYIZQONLCFLEV-DAELLWKTSA-N Aromasine Chemical compound O=C1C=C[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC(=C)C2=C1 BFYIZQONLCFLEV-DAELLWKTSA-N 0.000 claims description 4
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 claims description 4
- 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 4
- 239000002147 L01XE04 - Sunitinib Substances 0.000 claims description 4
- 239000002146 L01XE16 - Crizotinib Substances 0.000 claims description 4
- 229940124647 MEK inhibitor Drugs 0.000 claims description 4
- ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 4
- 239000012661 PARP inhibitor Substances 0.000 claims description 4
- 229940121906 Poly ADP ribose polymerase inhibitor Drugs 0.000 claims description 4
- 102100026715 Serine/threonine-protein kinase STK11 Human genes 0.000 claims description 4
- 229940028652 abraxane Drugs 0.000 claims description 4
- 229960002932 anastrozole Drugs 0.000 claims description 4
- YBBLVLTVTVSKRW-UHFFFAOYSA-N anastrozole Chemical compound N#CC(C)(C)C1=CC(C(C)(C#N)C)=CC(CN2N=CN=C2)=C1 YBBLVLTVTVSKRW-UHFFFAOYSA-N 0.000 claims description 4
- 229960004562 carboplatin Drugs 0.000 claims description 4
- 229960005061 crizotinib Drugs 0.000 claims description 4
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 claims description 4
- 229960003668 docetaxel Drugs 0.000 claims description 4
- 229960005167 everolimus Drugs 0.000 claims description 4
- 229960000255 exemestane Drugs 0.000 claims description 4
- PJZDLZXMGBOJRF-CXOZILEQSA-L folfirinox Chemical compound [Pt+4].[O-]C(=O)C([O-])=O.[NH-][C@H]1CCCC[C@@H]1[NH-].FC1=CNC(=O)NC1=O.C1NC=2NC(N)=NC(=O)C=2N(C=O)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1.C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 PJZDLZXMGBOJRF-CXOZILEQSA-L 0.000 claims description 4
- 229960002584 gefitinib Drugs 0.000 claims description 4
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 4
- 229960003881 letrozole Drugs 0.000 claims description 4
- HPJKCIUCZWXJDR-UHFFFAOYSA-N letrozole Chemical compound C1=CC(C#N)=CC=C1C(N1N=CN=C1)C1=CC=C(C#N)C=C1 HPJKCIUCZWXJDR-UHFFFAOYSA-N 0.000 claims description 4
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 4
- 229960003278 osimertinib Drugs 0.000 claims description 4
- DUYJMQONPNNFPI-UHFFFAOYSA-N osimertinib Chemical compound COC1=CC(N(C)CCN(C)C)=C(NC(=O)C=C)C=C1NC1=NC=CC(C=2C3=CC=CC=C3N(C)C=2)=N1 DUYJMQONPNNFPI-UHFFFAOYSA-N 0.000 claims description 4
- 229960005079 pemetrexed Drugs 0.000 claims description 4
- QOFFJEBXNKRSPX-ZDUSSCGKSA-N pemetrexed Chemical compound C1=N[C]2NC(N)=NC(=O)C2=C1CCC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 QOFFJEBXNKRSPX-ZDUSSCGKSA-N 0.000 claims description 4
- 229960001796 sunitinib Drugs 0.000 claims description 4
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 claims description 4
- 229960001603 tamoxifen Drugs 0.000 claims description 4
- 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 description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 3
- 229950003054 binimetinib Drugs 0.000 claims description 3
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 claims description 3
- 229960002271 cobimetinib Drugs 0.000 claims description 3
- RESIMIUSNACMNW-BXRWSSRYSA-N cobimetinib fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F.C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F RESIMIUSNACMNW-BXRWSSRYSA-N 0.000 claims description 3
- 201000005202 lung cancer Diseases 0.000 claims description 3
- 208000020816 lung neoplasm Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- -1 pembroluzimab Chemical compound 0.000 claims description 3
- 229920000371 poly(diallyldimethylammonium chloride) polymer Polymers 0.000 claims description 3
- 229950010746 selumetinib Drugs 0.000 claims description 3
- CYOHGALHFOKKQC-UHFFFAOYSA-N selumetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1Cl CYOHGALHFOKKQC-UHFFFAOYSA-N 0.000 claims description 3
- 229960004066 trametinib Drugs 0.000 claims description 3
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 claims description 3
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 3
- 102100034134 Activin receptor type-1B Human genes 0.000 claims description 2
- 108010014380 Autophagy-Related Protein-1 Homolog Proteins 0.000 claims description 2
- 102000016956 Autophagy-Related Protein-1 Homolog Human genes 0.000 claims description 2
- 102000052609 BRCA2 Human genes 0.000 claims description 2
- 108700020462 BRCA2 Proteins 0.000 claims description 2
- 101150008921 Brca2 gene Proteins 0.000 claims description 2
- 102100024458 Cyclin-dependent kinase inhibitor 2A Human genes 0.000 claims description 2
- 102100032610 Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas Human genes 0.000 claims description 2
- 101000799189 Homo sapiens Activin receptor type-1B Proteins 0.000 claims description 2
- 101001014590 Homo sapiens Guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas Proteins 0.000 claims description 2
- 101001014594 Homo sapiens Guanine nucleotide-binding protein G(s) subunit alpha isoforms short Proteins 0.000 claims description 2
- 101001014610 Homo sapiens Neuroendocrine secretory protein 55 Proteins 0.000 claims description 2
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 claims description 2
- 101000797903 Homo sapiens Protein ALEX Proteins 0.000 claims description 2
- 101000628562 Homo sapiens Serine/threonine-protein kinase STK11 Proteins 0.000 claims description 2
- 102000004034 Kelch-Like ECH-Associated Protein 1 Human genes 0.000 claims description 2
- 108090000484 Kelch-Like ECH-Associated Protein 1 Proteins 0.000 claims description 2
- 102100025725 Mothers against decapentaplegic homolog 4 Human genes 0.000 claims description 2
- 101710143112 Mothers against decapentaplegic homolog 4 Proteins 0.000 claims description 2
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 claims description 2
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 claims description 2
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 claims description 2
- 101710181599 Serine/threonine-protein kinase STK11 Proteins 0.000 claims description 2
- HWGQMRYQVZSGDQ-HZPDHXFCSA-N chembl3137320 Chemical compound CN1N=CN=C1[C@H]([C@H](N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-HZPDHXFCSA-N 0.000 claims description 2
- 230000006710 cytostatic response Effects 0.000 claims description 2
- 230000000593 degrading effect Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 claims description 2
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 claims description 2
- 230000035772 mutation Effects 0.000 claims description 2
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 claims description 2
- JTSLALYXYSRPGW-UHFFFAOYSA-N n-[5-(4-cyanophenyl)-1h-pyrrolo[2,3-b]pyridin-3-yl]pyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NC(C1=C2)=CNC1=NC=C2C1=CC=C(C#N)C=C1 JTSLALYXYSRPGW-UHFFFAOYSA-N 0.000 claims description 2
- PCHKPVIQAHNQLW-CQSZACIVSA-N niraparib Chemical compound N1=C2C(C(=O)N)=CC=CC2=CN1C(C=C1)=CC=C1[C@@H]1CCCNC1 PCHKPVIQAHNQLW-CQSZACIVSA-N 0.000 claims description 2
- 229950011068 niraparib Drugs 0.000 claims description 2
- FAQDUNYVKQKNLD-UHFFFAOYSA-N olaparib Chemical compound FC1=CC=C(CC2=C3[CH]C=CC=C3C(=O)N=N2)C=C1C(=O)N(CC1)CCN1C(=O)C1CC1 FAQDUNYVKQKNLD-UHFFFAOYSA-N 0.000 claims description 2
- 229960000572 olaparib Drugs 0.000 claims description 2
- 230000026731 phosphorylation Effects 0.000 claims description 2
- 238000006366 phosphorylation reaction Methods 0.000 claims description 2
- HMABYWSNWIZPAG-UHFFFAOYSA-N rucaparib Chemical compound C1=CC(CNC)=CC=C1C(N1)=C2CCNC(=O)C3=C2C1=CC(F)=C3 HMABYWSNWIZPAG-UHFFFAOYSA-N 0.000 claims description 2
- 229950004707 rucaparib Drugs 0.000 claims description 2
- 238000009097 single-agent therapy Methods 0.000 claims description 2
- 229950004550 talazoparib Drugs 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims description 2
- 238000000034 method Methods 0.000 description 65
- 208000016691 refractory malignant neoplasm Diseases 0.000 description 9
- 125000000217 alkyl group Chemical group 0.000 description 5
- 125000000753 cycloalkyl group Chemical group 0.000 description 5
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000004900 autophagic degradation Effects 0.000 description 3
- 229940124302 mTOR inhibitor Drugs 0.000 description 3
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 description 3
- 230000001594 aberrant effect Effects 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US202062977041P | 2020-02-14 | 2020-02-14 | |
| US62/977,041 | 2020-02-14 | ||
| PCT/US2021/018044 WO2021163633A1 (en) | 2020-02-14 | 2021-02-12 | Mono and combination therapies with ulk1/2 inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2023513797A JP2023513797A (ja) | 2023-04-03 |
| JP2023513797A5 JP2023513797A5 (https=) | 2024-02-20 |
| JPWO2021163633A5 true JPWO2021163633A5 (https=) | 2024-02-20 |
Family
ID=77292775
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2022549152A Pending JP2023513797A (ja) | 2020-02-14 | 2021-02-12 | Ｕｌｋ１／２阻害剤による単剤療法および併用療法 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US20230130766A1 (https=) |
| EP (1) | EP4103186A4 (https=) |
| JP (1) | JP2023513797A (https=) |
| KR (1) | KR20220154094A (https=) |
| CN (1) | CN115484956A (https=) |
| AU (1) | AU2021218740A1 (https=) |
| WO (1) | WO2021163633A1 (https=) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20220153582A (ko) | 2020-02-14 | 2022-11-18 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | 마크로시클릭 ulk1/2 억제제 |
| WO2022072668A1 (en) * | 2020-09-30 | 2022-04-07 | Salk Institute For Biological Studies | Patient selection biomarkers for treatment with ulk inhibitors |
| WO2024140401A1 (zh) * | 2022-12-30 | 2024-07-04 | 捷思英达控股有限公司 | 作为激酶抑制剂的杂环化合物以及包括其的组合物 |
| WO2025045182A1 (zh) * | 2023-09-01 | 2025-03-06 | 深圳众格生物科技有限公司 | Ulk1抑制剂及其制备方法和用途 |
| WO2025166124A1 (en) * | 2024-02-02 | 2025-08-07 | Deciphera Pharmaceuticals, Llc | Ulk inhibitors and methods of use thereof |
| WO2025166180A1 (en) * | 2024-02-02 | 2025-08-07 | Deciphera Pharmaceuticals, Llc | Ulk inhibitors and methods of use thereof |
| WO2025166161A1 (en) * | 2024-02-02 | 2025-08-07 | Deciphera Pharmaceuticals, Llc | Ulk inhibitors and methods of use thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA06013165A (es) * | 2004-05-14 | 2007-02-13 | Pfizer Prod Inc | Derivados de pirimidina para el tratamiento de crecimiento de celulas anormal. |
| WO2006037117A1 (en) * | 2004-09-27 | 2006-04-06 | Amgen Inc. | Substituted heterocyclic compounds and methods of use |
| DK3185868T3 (da) * | 2014-08-25 | 2022-05-23 | Salk Inst For Biological Studi | Hidtil ukendte ULK1-inhibitorer og fremgangsmåder til anvendelse af samme |
| RS62017B1 (sr) * | 2014-09-17 | 2021-07-30 | Celgene Car Llc | Mk2 inhibitori i njihova upotreba |
-
2021
- 2021-02-12 JP JP2022549152A patent/JP2023513797A/ja active Pending
- 2021-02-12 KR KR1020227028939A patent/KR20220154094A/ko active Pending
- 2021-02-12 US US17/799,641 patent/US20230130766A1/en active Pending
- 2021-02-12 WO PCT/US2021/018044 patent/WO2021163633A1/en not_active Ceased
- 2021-02-12 CN CN202180027793.4A patent/CN115484956A/zh active Pending
- 2021-02-12 AU AU2021218740A patent/AU2021218740A1/en active Pending
- 2021-02-12 EP EP21754343.8A patent/EP4103186A4/en not_active Withdrawn
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