JPWO2020142742A5 - - Google Patents
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- Publication number
- JPWO2020142742A5 JPWO2020142742A5 JP2021538976A JP2021538976A JPWO2020142742A5 JP WO2020142742 A5 JPWO2020142742 A5 JP WO2020142742A5 JP 2021538976 A JP2021538976 A JP 2021538976A JP 2021538976 A JP2021538976 A JP 2021538976A JP WO2020142742 A5 JPWO2020142742 A5 JP WO2020142742A5
- Authority
- JP
- Japan
- Prior art keywords
- aryl
- pharmaceutically acceptable
- acceptable salt
- compound
- alkyl
- 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.)
- Pending
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- 150000001875 compounds Chemical class 0.000 claims description 76
- 150000003839 salts Chemical class 0.000 claims description 75
- 125000003118 aryl group Chemical group 0.000 claims description 68
- 125000000623 heterocyclic group Chemical group 0.000 claims description 66
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 46
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 46
- 239000008194 pharmaceutical composition Substances 0.000 claims description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 34
- 238000000034 method Methods 0.000 claims description 33
- GBXQPDCOMJJCMJ-UHFFFAOYSA-M trimethyl-[6-(trimethylazaniumyl)hexyl]azanium;bromide Chemical compound [Br-].C[N+](C)(C)CCCCCC[N+](C)(C)C GBXQPDCOMJJCMJ-UHFFFAOYSA-M 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 201000010099 disease Diseases 0.000 claims description 18
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 16
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 16
- 208000035475 disorder Diseases 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 230000002401 inhibitory effect Effects 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- 210000004027 cell Anatomy 0.000 claims description 9
- 210000002950 fibroblast Anatomy 0.000 claims description 9
- 125000005914 C6-C14 aryloxy group Chemical group 0.000 claims description 8
- 150000001721 carbon Chemical group 0.000 claims description 8
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 8
- 206010028980 Neoplasm Diseases 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 102000003973 Fibroblast growth factor 21 Human genes 0.000 claims description 6
- 108090000376 Fibroblast growth factor 21 Proteins 0.000 claims description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 6
- 239000002207 metabolite Substances 0.000 claims description 6
- 230000001404 mediated effect Effects 0.000 claims description 5
- 230000035755 proliferation Effects 0.000 claims description 5
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims description 4
- -1 C 1 -C 6 alkyl Chemical group 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 102000023984 PPAR alpha Human genes 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 239000000556 agonist Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 230000000694 effects Effects 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 239000000411 inducer Substances 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 claims description 4
- 201000009030 Carcinoma Diseases 0.000 claims description 3
- 208000002705 Glucose Intolerance Diseases 0.000 claims description 3
- 206010018429 Glucose tolerance impaired Diseases 0.000 claims description 3
- 102000004877 Insulin Human genes 0.000 claims description 3
- 108090001061 Insulin Proteins 0.000 claims description 3
- 208000008589 Obesity Diseases 0.000 claims description 3
- 230000004913 activation Effects 0.000 claims description 3
- 208000037976 chronic inflammation Diseases 0.000 claims description 3
- 230000006020 chronic inflammation Effects 0.000 claims description 3
- 229940125396 insulin Drugs 0.000 claims description 3
- 235000020824 obesity Nutrition 0.000 claims description 3
- 102000004169 proteins and genes Human genes 0.000 claims description 3
- 108090000623 proteins and genes Proteins 0.000 claims description 3
- 230000007838 tissue remodeling Effects 0.000 claims description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 206010052747 Adenocarcinoma pancreas Diseases 0.000 claims description 2
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 206010006187 Breast cancer Diseases 0.000 claims description 2
- 208000026310 Breast neoplasm Diseases 0.000 claims description 2
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 2
- 206010009944 Colon cancer Diseases 0.000 claims description 2
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 208000011231 Crohn disease Diseases 0.000 claims description 2
- 102000005593 Endopeptidases Human genes 0.000 claims description 2
- 108010059378 Endopeptidases Proteins 0.000 claims description 2
- 102000018389 Exopeptidases Human genes 0.000 claims description 2
- 108010091443 Exopeptidases Proteins 0.000 claims description 2
- 201000008808 Fibrosarcoma Diseases 0.000 claims description 2
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229940076838 Immune checkpoint inhibitor Drugs 0.000 claims description 2
- 102000037984 Inhibitory immune checkpoint proteins Human genes 0.000 claims description 2
- 108091008026 Inhibitory immune checkpoint proteins Proteins 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims description 2
- 206010033128 Ovarian cancer Diseases 0.000 claims description 2
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 2
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 2
- 206010060862 Prostate cancer Diseases 0.000 claims description 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 2
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims description 2
- 208000009956 adenocarcinoma Diseases 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 230000003143 atherosclerotic effect Effects 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 230000008355 cartilage degradation Effects 0.000 claims description 2
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims description 2
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 2
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 230000002708 enhancing effect Effects 0.000 claims description 2
- 229960002297 fenofibrate Drugs 0.000 claims description 2
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 2
- 229940125753 fibrate Drugs 0.000 claims description 2
- 230000003176 fibrotic effect Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000028993 immune response Effects 0.000 claims description 2
- 239000012274 immune-checkpoint protein inhibitor Substances 0.000 claims description 2
- 208000011379 keloid formation Diseases 0.000 claims description 2
- 208000032839 leukemia Diseases 0.000 claims description 2
- 201000007270 liver cancer Diseases 0.000 claims description 2
- 208000014018 liver neoplasm Diseases 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 201000001441 melanoma Diseases 0.000 claims description 2
- 230000001394 metastastic effect Effects 0.000 claims description 2
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 2
- 201000008482 osteoarthritis Diseases 0.000 claims description 2
- 201000008968 osteosarcoma Diseases 0.000 claims description 2
- 201000002094 pancreatic adenocarcinoma Diseases 0.000 claims description 2
- 201000002528 pancreatic cancer Diseases 0.000 claims description 2
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 2
- 201000000849 skin cancer Diseases 0.000 claims description 2
- 210000004872 soft tissue Anatomy 0.000 claims description 2
- 206010041823 squamous cell carcinoma Diseases 0.000 claims description 2
- 230000004614 tumor growth Effects 0.000 claims description 2
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 2
- 230000029663 wound healing Effects 0.000 claims description 2
- 125000004438 haloalkoxy group Chemical group 0.000 claims 1
- 239000000126 substance Substances 0.000 description 7
- 208000008999 Giant Cell Carcinoma Diseases 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 201000000014 lung giant cell carcinoma Diseases 0.000 description 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201962788722P | 2019-01-04 | 2019-01-04 | |
| US62/788,722 | 2019-01-04 | ||
| US201962863853P | 2019-06-19 | 2019-06-19 | |
| US62/863,853 | 2019-06-19 | ||
| PCT/US2020/012260 WO2020142742A1 (en) | 2019-01-04 | 2020-01-03 | Inhibitors of fibroblast activation protein |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2022516555A JP2022516555A (ja) | 2022-02-28 |
| JP2022516555A5 JP2022516555A5 (https=) | 2023-01-11 |
| JPWO2020142742A5 true JPWO2020142742A5 (https=) | 2023-01-11 |
Family
ID=71404153
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2021538976A Pending JP2022516555A (ja) | 2019-01-04 | 2020-01-03 | 線維芽細胞活性化タンパク質の阻害剤 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20200216417A1 (https=) |
| EP (1) | EP3906024A4 (https=) |
| JP (1) | JP2022516555A (https=) |
| KR (1) | KR20210113634A (https=) |
| CN (1) | CN114126597A (https=) |
| AU (1) | AU2020204714A1 (https=) |
| BR (1) | BR112021011861A2 (https=) |
| CA (1) | CA3124525A1 (https=) |
| CL (1) | CL2021001739A1 (https=) |
| IL (1) | IL284434A (https=) |
| MX (1) | MX2021007948A (https=) |
| SG (1) | SG11202106399XA (https=) |
| WO (1) | WO2020142742A1 (https=) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN116474108A (zh) | 2016-12-14 | 2023-07-25 | 普渡研究基金会 | 成纤维细胞活化蛋白(fap)-靶向成像和治疗 |
| JP2021506972A (ja) | 2017-12-15 | 2021-02-22 | プラクシス バイオテック エルエルシー | 線維芽細胞活性化タンパク質の阻害剤 |
| EP3728228A1 (en) | 2017-12-22 | 2020-10-28 | Ravenna Pharmaceuticals, Inc. | Aminopyridine derivatives as phosphatidylinositol phosphate kinase inhibitors |
| CN113811529A (zh) | 2018-12-21 | 2021-12-17 | 普拉西斯生物技术有限责任公司 | 成纤维细胞激活蛋白抑制剂 |
| TW202112767A (zh) | 2019-06-17 | 2021-04-01 | 美商佩特拉製藥公司 | 作為磷脂酸肌醇磷酸激酶抑制劑之胺基吡啶衍生物 |
| WO2020254559A1 (en) | 2019-06-19 | 2020-12-24 | Nmd Pharma A/S | Compounds for the treatment of neuromuscular disorders |
| WO2021155292A1 (en) * | 2020-01-31 | 2021-08-05 | Philip Stewart Low | Fibroblast activation protein (fap) - targeted antifibrotic therapy |
| CN119798158B (zh) * | 2022-08-02 | 2025-10-17 | 中国科学院上海应用物理研究所 | 一种含苯并吡啶环类化合物及其制备方法 |
| WO2025159534A1 (ko) * | 2024-01-24 | 2025-07-31 | 서울대학교산학협력단 | 3-스티릴피리딘 구조 기반의 섬유아세포 활성화 단백질 표적 물질 |
| CN118978511A (zh) * | 2024-08-02 | 2024-11-19 | 江苏华益科技有限公司 | 一种靶向fap化合物及其制备方法 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1943257A2 (en) * | 2005-05-19 | 2008-07-16 | Genentech, Inc. | Fibroblast activation protein inhibitor compounds and methods |
| AU2006278039B2 (en) * | 2005-08-11 | 2010-10-21 | F. Hoffmann-La Roche Ag | Pharmaceutical composition comprising a DPP-lV inhibitor |
| WO2013107820A1 (en) * | 2012-01-17 | 2013-07-25 | Universiteit Antwerpen | Novel fap inhibitors |
| JP2021506972A (ja) * | 2017-12-15 | 2021-02-22 | プラクシス バイオテック エルエルシー | 線維芽細胞活性化タンパク質の阻害剤 |
| CN113811529A (zh) * | 2018-12-21 | 2021-12-17 | 普拉西斯生物技术有限责任公司 | 成纤维细胞激活蛋白抑制剂 |
-
2020
- 2020-01-03 BR BR112021011861-6A patent/BR112021011861A2/pt not_active Application Discontinuation
- 2020-01-03 EP EP20735966.2A patent/EP3906024A4/en not_active Withdrawn
- 2020-01-03 AU AU2020204714A patent/AU2020204714A1/en not_active Abandoned
- 2020-01-03 JP JP2021538976A patent/JP2022516555A/ja active Pending
- 2020-01-03 CA CA3124525A patent/CA3124525A1/en active Pending
- 2020-01-03 US US16/734,214 patent/US20200216417A1/en not_active Abandoned
- 2020-01-03 MX MX2021007948A patent/MX2021007948A/es unknown
- 2020-01-03 CN CN202080007971.2A patent/CN114126597A/zh active Pending
- 2020-01-03 KR KR1020217024699A patent/KR20210113634A/ko not_active Ceased
- 2020-01-03 SG SG11202106399XA patent/SG11202106399XA/en unknown
- 2020-01-03 WO PCT/US2020/012260 patent/WO2020142742A1/en not_active Ceased
-
2021
- 2021-06-28 IL IL284434A patent/IL284434A/en unknown
- 2021-06-29 CL CL2021001739A patent/CL2021001739A1/es unknown
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