CA2995909A1 - Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors - Google Patents
Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors Download PDFInfo
- Publication number
- CA2995909A1 CA2995909A1 CA2995909A CA2995909A CA2995909A1 CA 2995909 A1 CA2995909 A1 CA 2995909A1 CA 2995909 A CA2995909 A CA 2995909A CA 2995909 A CA2995909 A CA 2995909A CA 2995909 A1 CA2995909 A1 CA 2995909A1
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- Prior art keywords
- alkyl
- compound according
- mmol
- fluoro
- reaction mixture
- 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.)
- Abandoned
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- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 title description 9
- 150000002391 heterocyclic compounds Chemical class 0.000 title 1
- 239000002935 phosphatidylinositol 3 kinase inhibitor Substances 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 119
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 8
- 239000000203 mixture Substances 0.000 claims description 58
- 125000000217 alkyl group Chemical group 0.000 claims description 55
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 41
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims description 25
- -1 C1-alkoxy Chemical group 0.000 claims description 25
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 20
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 125000003282 alkyl amino group Chemical group 0.000 claims description 19
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
- 229910052717 sulfur Inorganic materials 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000006832 (C1-C10) alkylene group Chemical group 0.000 claims description 15
- 125000000304 alkynyl group Chemical group 0.000 claims description 15
- 125000003342 alkenyl group Chemical group 0.000 claims description 14
- 125000004450 alkenylene group Chemical group 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 125000005843 halogen group Chemical group 0.000 claims description 12
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 12
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000004434 sulfur atom Chemical group 0.000 claims description 11
- 125000002252 acyl group Chemical group 0.000 claims description 10
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 8
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- MVUXANSDGPVLLZ-UHFFFAOYSA-N tert-butyl 4-bromo-5-propan-2-yloxyindole-1-carboxylate Chemical compound CC(C)Oc1ccc2n(ccc2c1Br)C(=O)OC(C)(C)C MVUXANSDGPVLLZ-UHFFFAOYSA-N 0.000 description 1
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- KYCVRKPFNLCHLL-UHFFFAOYSA-N tert-butyl 5-aminoindole-1-carboxylate Chemical compound NC1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 KYCVRKPFNLCHLL-UHFFFAOYSA-N 0.000 description 1
- BYFYKCHJFIWCPC-UHFFFAOYSA-N tert-butyl 5-hydroxyindole-1-carboxylate Chemical compound OC1=CC=C2N(C(=O)OC(C)(C)C)C=CC2=C1 BYFYKCHJFIWCPC-UHFFFAOYSA-N 0.000 description 1
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- 238000003354 tissue distribution assay Methods 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- GQMVAUFIUVHMBB-UHFFFAOYSA-K trinaphthalen-2-yloxybismuthane Chemical compound C1=CC=CC2=CC(O[Bi](OC=3C=C4C=CC=CC4=CC=3)OC=3C=C4C=CC=CC4=CC=3)=CC=C21 GQMVAUFIUVHMBB-UHFFFAOYSA-K 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- 238000002255 vaccination Methods 0.000 description 1
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- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
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- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
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- 239000003039 volatile agent Substances 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Immunology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1514754.9A GB201514754D0 (en) | 2015-08-19 | 2015-08-19 | Compounds |
| GB1514754.9 | 2015-08-19 | ||
| PCT/GB2016/052581 WO2017029521A1 (en) | 2015-08-19 | 2016-08-19 | Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors |
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| CA2995909A1 true CA2995909A1 (en) | 2017-02-23 |
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| CA2995909A Abandoned CA2995909A1 (en) | 2015-08-19 | 2016-08-19 | Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors |
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| Country | Link |
|---|---|
| US (1) | US10442815B2 (enExample) |
| EP (1) | EP3337807A1 (enExample) |
| JP (1) | JP2018528942A (enExample) |
| CN (1) | CN108349988B (enExample) |
| AU (1) | AU2016307889A1 (enExample) |
| CA (1) | CA2995909A1 (enExample) |
| GB (1) | GB201514754D0 (enExample) |
| MX (1) | MX2018001992A (enExample) |
| WO (1) | WO2017029521A1 (enExample) |
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| NZ597983A (en) | 2009-08-20 | 2014-05-30 | Karus Therapeutics Ltd | Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors |
| GB201204125D0 (en) | 2012-03-08 | 2012-04-25 | Karus Therapeutics Ltd | Compounds |
| GB201402431D0 (en) | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
| GB201514760D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
| GB201514754D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514751D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514758D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Formulation |
| JP7290627B2 (ja) | 2017-08-17 | 2023-06-13 | ボード オブ レジェンツ，ザ ユニバーシティ オブ テキサス システム | Ａｔｒキナーゼの複素環式阻害剤 |
| GB201909468D0 (en) | 2019-07-01 | 2019-08-14 | Karus Therapeutics Ltd | Compounds for treating cancer |
| WO2021113633A1 (en) | 2019-12-05 | 2021-06-10 | Verge Analytics, Inc. | Fused tricyclic heterocyclic compounds as inhibitors of pikfyve kinase useful for the treatment of neurological diseases |
| US12486274B2 (en) | 2020-01-13 | 2025-12-02 | Verge Analytics, Inc. | Substituted pyrazolo-pyrimidines and uses thereof |
| WO2022169882A1 (en) | 2021-02-03 | 2022-08-11 | Verge Analytics, Inc. | Methods and treatment of viral infection caused by sars-cov-2 |
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| DE1445742A1 (de) | 1963-11-06 | 1968-12-19 | Bayer Ag | Verfahren zur Herstellung von 2-Stellung substituierten Benzoxazinonen |
| US4017500A (en) | 1973-07-16 | 1977-04-12 | Schering Corporation | Certain 8-amino-1,7-naphthyridines |
| US5703075A (en) | 1988-12-21 | 1997-12-30 | Pharmacia & Upjohn Company | Antiatherosclerotic and antithrombotic 1-benzopyran-4-ones and 2-amino-1,3-benzoxazine-4-ones |
| US6608053B2 (en) | 2000-04-27 | 2003-08-19 | Yamanouchi Pharmaceutical Co., Ltd. | Fused heteroaryl derivatives |
| AU5261001A (en) | 2000-04-27 | 2001-11-12 | Imperial Cancer Research Technology Ltd | Condensed heteroaryl derivatives |
| WO2002002551A1 (en) | 2000-06-30 | 2002-01-10 | Sugen, Inc. | 4-heteroaryl-3-heteroarylidenyl-2-indolinones and their use as protein kinase inhibitors |
| US6905669B2 (en) | 2001-04-24 | 2005-06-14 | Supergen, Inc. | Compositions and methods for reestablishing gene transcription through inhibition of DNA methylation and histone deacetylase |
| EP1521747B1 (en) | 2002-07-15 | 2018-09-05 | Symphony Evolution, Inc. | Receptor-type kinase modulators and methods of use |
| FR2846657B1 (fr) | 2002-11-05 | 2004-12-24 | Servier Lab | Nouveaux composes pyridopyrimidinone, leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
| CA2557541C (en) | 2004-02-26 | 2014-12-16 | Aska Pharmaceutical Co., Ltd. | Pyrimidine derivatives |
| GB0423653D0 (en) | 2004-10-25 | 2004-11-24 | Piramed Ltd | Pharmaceutical compounds |
| JP2008545660A (ja) | 2005-05-20 | 2008-12-18 | バーテックス ファーマシューティカルズ インコーポレイテッド | プロテインキナーゼ阻害剤として有用なピロロピリジン化合物 |
| WO2007084667A2 (en) | 2006-01-19 | 2007-07-26 | Osi Pharmaceutical, Inc. | Fused heterobicyclic kinase inhibitors |
| KR20090021155A (ko) | 2006-04-26 | 2009-02-27 | 에프. 호프만-라 로슈 아게 | Ｐｉ3ｋ 억제제로서의 피리미딘 유도체 |
| AU2007243466B2 (en) | 2006-04-26 | 2012-01-19 | F. Hoffmann-La Roche Ag | Phosphoinositide 3-kinase inhibitor compounds and pharmaceutical compositions containing them |
| WO2008001076A1 (en) * | 2006-06-26 | 2008-01-03 | Ucb Pharma S.A. | Fused thiazole derivatives as kinase inhibitors |
| EP2441768A1 (en) | 2006-11-13 | 2012-04-18 | Eli Lilly & Co. | Thienopyrimidinones for treatment of inflammatory disorders and cancers |
| EP2121613A2 (en) | 2007-01-31 | 2009-11-25 | Vertex Pharmaceuticals, Inc. | 2-aminopyridine derivatives useful as kinase inhibitors |
| EP2139332A4 (en) | 2007-03-28 | 2010-04-21 | Merck Sharp & Dohme | SUBSTITUTED PYRIDO [2,3-D] PYRIMIDIN DERIVATIVES AS CANNABINOID-1 RECEPTOR MODULATORS |
| EP2154965A4 (en) | 2007-05-29 | 2011-08-17 | Glaxosmithkline Llc | NAPHTHYRIDINE DERIVATIVES AS P13 KINASE INHIBITORS |
| GB0710528D0 (en) | 2007-06-01 | 2007-07-11 | Glaxo Group Ltd | Novel compounds |
| JP2011529932A (ja) | 2008-08-05 | 2011-12-15 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 置換ナフチリジン及び医薬としてのその使用 |
| WO2010037765A2 (en) | 2008-10-03 | 2010-04-08 | Merck Serono S.A. | 4-morpholino-pyrido[3,2-d]pyrimidines |
| GB2465405A (en) * | 2008-11-10 | 2010-05-19 | Univ Basel | Triazine, pyrimidine and pyridine analogues and their use in therapy |
| US8981087B2 (en) | 2009-07-29 | 2015-03-17 | Karus Therapeutics Limited | Benzo [E] [1,3] oxazin-4-one derivatives as phosphoinositide 3-kinase inhibitors |
| NZ597983A (en) * | 2009-08-20 | 2014-05-30 | Karus Therapeutics Ltd | Tricyclic heterocyclic compounds as phosphoinositide 3-kinase inhibitors |
| WO2011079231A1 (en) | 2009-12-23 | 2011-06-30 | Gatekeeper Pharmaceutical, Inc. | Compounds that modulate egfr activity and methods for treating or preventing conditions therewith |
| GB201007347D0 (en) | 2010-04-30 | 2010-06-16 | Karus Therapeutics Ltd | Compounds |
| DK3686193T3 (da) | 2011-07-27 | 2022-05-30 | Astrazeneca Ab | 2-(2,4,5-substitueret anilino)pyrimidinforbindelser |
| WO2013017480A1 (en) | 2011-07-29 | 2013-02-07 | Cellzome Limited | Pyrazolo[4,3-c]pyridine derivatives as jak inhibitors |
| GB201204125D0 (en) | 2012-03-08 | 2012-04-25 | Karus Therapeutics Ltd | Compounds |
| EP3181564B1 (en) | 2012-11-20 | 2019-09-18 | H. Hoffnabb-La Roche Ag | Aminopyrimidine compounds as inhibitors of t790m containing egfr mutants |
| SI2994465T1 (sl) | 2013-05-10 | 2018-10-30 | Karus Therapeutics Limited | Novi inhibitorji histon deacetilaze |
| KR20160013204A (ko) | 2013-05-30 | 2016-02-03 | 인피니티 파마슈티칼스, 인코포레이티드 | Pi3 키나아제 동형단백질 조절제를 사용하는 암의 치료 |
| WO2014210354A1 (en) * | 2013-06-28 | 2014-12-31 | Genentech, Inc. | Azaindazole compounds as inhibitors of t790m containing egfr mutants |
| ES2818933T3 (es) | 2013-10-10 | 2021-04-14 | Acetylon Pharmaceuticals Inc | Inhibidores de la HDAC en combinación con los inhibidores de la pi3k, para el tratamiento del linfoma no Hodgkin |
| GB201321730D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321738D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic Agents |
| GB201321729D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201321728D0 (en) * | 2013-12-09 | 2014-01-22 | Ucb Pharma Sa | Therapeutic agents |
| GB201402431D0 (en) * | 2014-02-12 | 2014-03-26 | Karus Therapeutics Ltd | Compounds |
| GB201514751D0 (en) * | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514756D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compound and method of use |
| GB201514758D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Formulation |
| GB201514754D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds |
| GB201514760D0 (en) | 2015-08-19 | 2015-09-30 | Karus Therapeutics Ltd | Compounds and method of use |
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2016
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- 2016-08-19 CA CA2995909A patent/CA2995909A1/en not_active Abandoned
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Also Published As
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| MX2018001992A (es) | 2018-06-19 |
| CN108349988A (zh) | 2018-07-31 |
| CN108349988B (zh) | 2021-10-01 |
| WO2017029521A1 (en) | 2017-02-23 |
| EP3337807A1 (en) | 2018-06-27 |
| US20180244685A1 (en) | 2018-08-30 |
| AU2016307889A1 (en) | 2018-03-08 |
| JP2018528942A (ja) | 2018-10-04 |
| GB201514754D0 (en) | 2015-09-30 |
| US10442815B2 (en) | 2019-10-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20220301 |