AU2015306458B2 - Indazoles - Google Patents
Indazoles Download PDFInfo
- Publication number
- AU2015306458B2 AU2015306458B2 AU2015306458A AU2015306458A AU2015306458B2 AU 2015306458 B2 AU2015306458 B2 AU 2015306458B2 AU 2015306458 A AU2015306458 A AU 2015306458A AU 2015306458 A AU2015306458 A AU 2015306458A AU 2015306458 B2 AU2015306458 B2 AU 2015306458B2
- Authority
- AU
- Australia
- Prior art keywords
- methanone
- phenyl
- methyl
- pyrrolidin
- pyrazolo
- 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.)
- Ceased
Links
- 150000002473 indoazoles Chemical class 0.000 title description 4
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 20
- 201000011510 cancer Diseases 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims abstract description 12
- 230000003463 hyperproliferative effect Effects 0.000 claims abstract description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 8
- 201000010099 disease Diseases 0.000 claims abstract description 7
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 claims description 201
- 150000001875 compounds Chemical class 0.000 claims description 136
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 106
- -1 acetamido, 2-hydroxyethyl Chemical group 0.000 claims description 103
- 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 96
- 238000000034 method Methods 0.000 claims description 86
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- 150000003839 salts Chemical class 0.000 claims description 38
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 31
- 102100024456 Cyclin-dependent kinase 8 Human genes 0.000 claims description 29
- 101000980937 Homo sapiens Cyclin-dependent kinase 8 Proteins 0.000 claims description 29
- 229910052801 chlorine Inorganic materials 0.000 claims description 26
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 24
- 239000012453 solvate Substances 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
- 229910052794 bromium Inorganic materials 0.000 claims description 20
- 125000006413 ring segment Chemical group 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 210000004027 cell Anatomy 0.000 claims description 13
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 13
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 239000004480 active ingredient Substances 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 8
- 208000032839 leukemia Diseases 0.000 claims description 8
- 229920006395 saturated elastomer Polymers 0.000 claims description 8
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 210000000066 myeloid cell Anatomy 0.000 claims description 7
- 210000000481 breast Anatomy 0.000 claims description 6
- 210000001072 colon Anatomy 0.000 claims description 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 230000000694 effects Effects 0.000 claims description 6
- 229910052740 iodine Inorganic materials 0.000 claims description 6
- 201000001441 melanoma Diseases 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
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- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
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- GHDVGYOWJVANGE-HNNXBMFYSA-N ClC1=CC=C(C=C1)[C@H]1N(CCC1)C(=O)C=1C=C2C(=NC=1)NN=C2OC Chemical compound ClC1=CC=C(C=C1)[C@H]1N(CCC1)C(=O)C=1C=C2C(=NC=1)NN=C2OC GHDVGYOWJVANGE-HNNXBMFYSA-N 0.000 claims description 4
- 208000007766 Kaposi sarcoma Diseases 0.000 claims description 4
- 208000034578 Multiple myelomas Diseases 0.000 claims description 4
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims description 4
- PAUXJRUOCRBJHR-UHFFFAOYSA-N NC1=NNC2=CC=C(C=C12)C(=O)N1C(CCC1)C1=CC=C(C=C1)Cl Chemical compound NC1=NNC2=CC=C(C=C12)C(=O)N1C(CCC1)C1=CC=C(C=C1)Cl PAUXJRUOCRBJHR-UHFFFAOYSA-N 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 230000003213 activating effect Effects 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 210000004556 brain Anatomy 0.000 claims description 4
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 4
- 230000001684 chronic effect Effects 0.000 claims description 4
- 230000002496 gastric effect Effects 0.000 claims description 4
- 210000003734 kidney Anatomy 0.000 claims description 4
- 210000004185 liver Anatomy 0.000 claims description 4
- 230000002611 ovarian Effects 0.000 claims description 4
- 210000002307 prostate Anatomy 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 230000002381 testicular Effects 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
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- KMCPIJPJZCDCMY-FQEVSTJZSA-N BrC1=CC=C(C=C1)[C@H]1N(CCC1)C(=O)C=1C=C2C(=NNC2=CC=1)CCC Chemical compound BrC1=CC=C(C=C1)[C@H]1N(CCC1)C(=O)C=1C=C2C(=NNC2=CC=1)CCC KMCPIJPJZCDCMY-FQEVSTJZSA-N 0.000 claims description 3
- YFRGYWOOWLDSGP-UHFFFAOYSA-N ClC1=C(C=C(C=C1)C1N(CCC1)C(=O)C1=CC=C2C(=N1)C(=NN2)C)F Chemical compound ClC1=C(C=C(C=C1)C1N(CCC1)C(=O)C1=CC=C2C(=N1)C(=NN2)C)F YFRGYWOOWLDSGP-UHFFFAOYSA-N 0.000 claims description 3
- VMSOGMBHDNROTJ-NRFANRHFSA-N ClC1=CC=C(C=C1)[C@H]1N(CCC1)C(=O)C=1C=C2C(=NNC2=CC=1)CC(C)C Chemical compound ClC1=CC=C(C=C1)[C@H]1N(CCC1)C(=O)C=1C=C2C(=NNC2=CC=1)CC(C)C VMSOGMBHDNROTJ-NRFANRHFSA-N 0.000 claims description 3
- 102100033145 Cyclin-dependent kinase 19 Human genes 0.000 claims description 3
- 101000944345 Homo sapiens Cyclin-dependent kinase 19 Proteins 0.000 claims description 3
- MONHZYRUJIRNID-AWEZNQCLSA-N NC1=NNC2=NC=C(C=C21)C(=O)N1[C@@H](CCC1)C1=CC=C(C=C1)Br Chemical compound NC1=NNC2=NC=C(C=C21)C(=O)N1[C@@H](CCC1)C1=CC=C(C=C1)Br MONHZYRUJIRNID-AWEZNQCLSA-N 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
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- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
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- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 2
- VSIKBMSMNYEKJE-UHFFFAOYSA-N (3-amino-1H-indazol-5-yl)-[3-(4-chlorophenyl)pyrrolidin-1-yl]methanone Chemical compound NC1=NNC2=CC=C(C=C12)C(=O)N1CC(CC1)C1=CC=C(C=C1)Cl VSIKBMSMNYEKJE-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- A—HUMAN NECESSITIES
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- A—HUMAN NECESSITIES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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- A—HUMAN NECESSITIES
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- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
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- A—HUMAN NECESSITIES
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P35/02—Antineoplastic agents specific for leukemia
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/54—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings condensed with carbocyclic rings or ring systems
- C07D231/56—Benzopyrazoles; Hydrogenated benzopyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D403/06—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 linked by a carbon chain containing only aliphatic carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Hematology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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EP14002929.9 | 2014-08-22 | ||
EP14002929 | 2014-08-22 | ||
PCT/EP2015/001570 WO2016026549A1 (en) | 2014-08-22 | 2015-07-30 | Indazoles |
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AU2015306458A1 AU2015306458A1 (en) | 2017-04-06 |
AU2015306458B2 true AU2015306458B2 (en) | 2019-05-02 |
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KR101731624B1 (ko) | 2014-07-01 | 2017-05-04 | 광주과학기술원 | 세포 리프로그래밍 유도용 조성물 |
MX2020001531A (es) * | 2017-08-07 | 2020-03-20 | Biocad Joint Stock Co | Nuevos compuestos hetorociclicos como inhibidores de cdk8/19. |
EP3691642B1 (en) | 2017-10-02 | 2024-03-06 | Boehringer Ingelheim International GmbH | [1,6]naphthyridine compounds and derivatives as cdk8/cdk19 inhibitors |
JOP20210324A1 (ar) * | 2019-06-27 | 2023-01-30 | Biogen Ma Inc | مشتقات من 2h-indazole واستخدامها في علاج مرض |
EP4255904A2 (en) * | 2020-12-03 | 2023-10-11 | Domain Therapeutics | Novel par-2 inhibitors |
CN116888120A (zh) | 2020-12-16 | 2023-10-13 | 美国安进公司 | Prmts抑制剂 |
WO2024148247A2 (en) * | 2023-01-06 | 2024-07-11 | Ajax Therapeutics, Inc. | Azaindazoles as jak2 inhibitors |
Citations (1)
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US20110034441A1 (en) * | 2009-08-10 | 2011-02-10 | Epitherix, Llc | Indazoles as wnt/b-catenin signaling pathway inhibitors and therapeutic uses thereof |
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EP1043998B1 (en) * | 1997-12-13 | 2007-03-07 | Bristol-Myers Squibb Company | USE OF PYRAZOLO [3,4-b] PYRIDINE AS CYCLIN DEPENDANT KINASE INHIBITORS |
JP2004507455A (ja) * | 2000-04-25 | 2004-03-11 | ブリストル−マイヤーズ スクイブ カンパニー | サイクリン依存性キナーゼ阻害剤としての、5−チオ−、スルフィニル−およびスルホニルピラゾロ[3,4−b]−ピリジンの用途 |
EP2001480A4 (en) * | 2006-03-31 | 2011-06-15 | Abbott Lab | Indazole CONNECTIONS |
WO2011000566A2 (en) * | 2009-06-30 | 2011-01-06 | Savira Pharmaceuticals Gmbh | Compounds and pharmaceutical compositions for the treatment of negative-sense ssrna virus infections |
CA2885392A1 (en) * | 2012-12-10 | 2014-06-19 | Zhanling CHENG | Novel bi-ring phenyl-pyridines/pyrazines for the treatment of cancer |
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US20110034441A1 (en) * | 2009-08-10 | 2011-02-10 | Epitherix, Llc | Indazoles as wnt/b-catenin signaling pathway inhibitors and therapeutic uses thereof |
Also Published As
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CN106573932A (zh) | 2017-04-19 |
WO2016026549A1 (en) | 2016-02-25 |
CA2958508A1 (en) | 2016-02-25 |
IL250306B (en) | 2019-01-31 |
EP3183239A1 (en) | 2017-06-28 |
US9862717B2 (en) | 2018-01-09 |
JP2017525717A (ja) | 2017-09-07 |
IL250306A0 (en) | 2017-03-30 |
JP6434614B2 (ja) | 2018-12-05 |
US20170267675A1 (en) | 2017-09-21 |
ES2703851T3 (es) | 2019-03-12 |
AU2015306458A1 (en) | 2017-04-06 |
EP3183239B1 (en) | 2018-09-26 |
CN106573932B (zh) | 2019-07-30 |
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