CA2856759A1 - 3-phenyl-isoquinolin-1(2h)-one derivatives as parp-1 inhibitors - Google Patents
3-phenyl-isoquinolin-1(2h)-one derivatives as parp-1 inhibitors Download PDFInfo
- Publication number
- CA2856759A1 CA2856759A1 CA2856759A CA2856759A CA2856759A1 CA 2856759 A1 CA2856759 A1 CA 2856759A1 CA 2856759 A CA2856759 A CA 2856759A CA 2856759 A CA2856759 A CA 2856759A CA 2856759 A1 CA2856759 A1 CA 2856759A1
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- Prior art keywords
- formula
- compound
- fluoro
- ethoxy
- amino
- 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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- 239000003112 inhibitor Substances 0.000 title description 8
- 101100407073 Caenorhabditis elegans parp-1 gene Proteins 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 213
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- BFKWTRSPEOOLOY-UHFFFAOYSA-N 4-(2-aminoethoxy)-7-fluoro-3-(3-methoxyphenyl)-2h-isoquinolin-1-one Chemical compound COC1=CC=CC(C2=C(C3=CC=C(F)C=C3C(=O)N2)OCCN)=C1 BFKWTRSPEOOLOY-UHFFFAOYSA-N 0.000 claims description 2
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- LBJDVUTVRADCSQ-UHFFFAOYSA-N tert-butyl N-[2-[[7-fluoro-1-oxo-3-[3-(trifluoromethyl)phenyl]-2H-isoquinolin-4-yl]oxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOc1c([nH]c(=O)c2cc(F)ccc12)-c1cccc(c1)C(F)(F)F LBJDVUTVRADCSQ-UHFFFAOYSA-N 0.000 description 1
- ZMZRSMWESPEHJD-UHFFFAOYSA-N tert-butyl N-[2-[[7-fluoro-3-(4-fluorophenyl)-1-oxo-2H-isoquinolin-4-yl]oxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOc1c([nH]c(=O)c2cc(F)ccc12)-c1ccc(F)cc1 ZMZRSMWESPEHJD-UHFFFAOYSA-N 0.000 description 1
- PMAUMWKKQSXPHO-UHFFFAOYSA-N tert-butyl N-[2-[[7-fluoro-3-(4-methylsulfonylphenyl)-1-oxo-2H-isoquinolin-4-yl]oxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOc1c([nH]c(=O)c2cc(F)ccc12)-c1ccc(cc1)S(C)(=O)=O PMAUMWKKQSXPHO-UHFFFAOYSA-N 0.000 description 1
- RSEJJQVZDOKLKZ-UHFFFAOYSA-N tert-butyl N-[2-[[7-fluoro-3-(4-morpholin-4-ylphenyl)-1-oxo-2H-isoquinolin-4-yl]oxy]ethyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCOc1c([nH]c(=O)c2cc(F)ccc12)-c1ccc(cc1)N1CCOCC1 RSEJJQVZDOKLKZ-UHFFFAOYSA-N 0.000 description 1
- GPTXCAZYUMDUMN-UHFFFAOYSA-N tert-butyl n-(2-hydroxyethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCO GPTXCAZYUMDUMN-UHFFFAOYSA-N 0.000 description 1
- CBDKQYKMCICBOF-UHFFFAOYSA-N thiazoline Chemical compound C1CN=CS1 CBDKQYKMCICBOF-UHFFFAOYSA-N 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229940044693 topoisomerase inhibitor Drugs 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 230000005747 tumor angiogenesis Effects 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- JNAHVYVRKWKWKQ-CYBMUJFWSA-N veliparib Chemical compound N=1C2=CC=CC(C(N)=O)=C2NC=1[C@@]1(C)CCCN1 JNAHVYVRKWKWKQ-CYBMUJFWSA-N 0.000 description 1
- 229950011257 veliparib Drugs 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000003039 volatile agent Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000013585 weight reducing agent Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940102001 zinc bromide Drugs 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D401/10—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 aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/41—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
- A61K31/4188—1,3-Diazoles condensed with other heterocyclic ring systems, e.g. biotin, sorbinil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11190687 | 2011-11-25 | ||
| EP11190687.1 | 2011-11-25 | ||
| EP12161489.5 | 2012-03-27 | ||
| EP12161489 | 2012-03-27 | ||
| PCT/EP2012/073125 WO2013076090A1 (en) | 2011-11-25 | 2012-11-20 | 3-phenyl-isoquinolin-1(2h)-one derivatives as parp-1 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2856759A1 true CA2856759A1 (en) | 2013-05-30 |
Family
ID=47227787
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2856759A Abandoned CA2856759A1 (en) | 2011-11-25 | 2012-11-20 | 3-phenyl-isoquinolin-1(2h)-one derivatives as parp-1 inhibitors |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US9422243B2 (enExample) |
| EP (1) | EP2788328B1 (enExample) |
| JP (1) | JP6106182B2 (enExample) |
| KR (1) | KR20140097457A (enExample) |
| CN (1) | CN103946214B (enExample) |
| AU (1) | AU2012342562B2 (enExample) |
| BR (1) | BR112014012031A2 (enExample) |
| CA (1) | CA2856759A1 (enExample) |
| CL (1) | CL2014001323A1 (enExample) |
| EA (1) | EA027800B1 (enExample) |
| ES (1) | ES2676068T3 (enExample) |
| IN (1) | IN2014CN04671A (enExample) |
| MX (1) | MX2014006015A (enExample) |
| WO (1) | WO2013076090A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2696572C2 (ru) | 2012-03-07 | 2019-08-05 | Инститьют Оф Кансер Ресёрч: Ройял Кансер Хоспитал (Зе) | 3-арил-5-замещенные соединения изохинолин-1-она и их терапевтическое применение |
| CA2922469A1 (en) | 2013-09-11 | 2015-03-19 | Institute Of Cancer Research: Royal Cancer Hospital (The) | 3-aryl-5-substituted-isoquinolin-1-one compounds and their therapeutic use |
| JP6663350B2 (ja) * | 2014-01-16 | 2020-03-11 | クロヴィス・オンコロジー，インコーポレーテッド | ヘテロ接合性の喪失を示す乳癌または卵巣癌の患者を治療するためのｐａｒｐ阻害剤の使用 |
| JP6917989B2 (ja) | 2015-11-06 | 2021-08-11 | ニューロクライン バイオサイエンシーズ，インコーポレイテッド | 神経学的疾患を処置するためのムスカリン受容体４（ｍ４）アンタゴニストとしての、ｎ−［２−（１−ベンジルピペリジン−４−イル）エチル］−４−（ピラジン−２−イル）−ピペラジン−１−カルボキサミド誘導体および関連化合物 |
| US12486250B2 (en) | 2019-12-06 | 2025-12-02 | Neurocrine Biosciences, Inc. | Muscarinic receptor 4 antagonists and methods of use |
| KR20250023494A (ko) | 2022-06-15 | 2025-02-18 | 아스트라제네카 아베 | 암 치료를 위한 병용 요법 |
| JP2026515235A (ja) | 2023-05-11 | 2026-05-14 | アストラゼネカ・アクチエボラーグ | 癌を治療するためのｐａｒｐ１阻害剤と選択的エストロゲン分解薬の併用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002090334A1 (en) * | 2001-05-08 | 2002-11-14 | Kudos Pharmaceuticals Limited | Isoquinolinone derivatives as parp inhibitors |
| US20040176361A1 (en) * | 2001-05-23 | 2004-09-09 | Masakazu Fujio | Fused heterocyclic compound and medicinal use thereof |
| AU2003255149A1 (en) * | 2002-07-24 | 2004-02-09 | Kyorin Pharmaceutical Co., Ltd. | 4-(substituted aryl)-5-hydroxyisoquinolinone derivative |
| WO2009104802A1 (en) * | 2008-02-22 | 2009-08-27 | Banyu Pharmaceutical Co., Ltd. | Novel aminopyridine derivatives having aurora a selective inhibitory action |
| TWI499418B (zh) * | 2009-05-21 | 2015-09-11 | Nerviano Medical Sciences Srl | 異喹啉－１（２ｈ）－酮衍生物 |
-
2012
- 2012-11-20 EP EP12791464.6A patent/EP2788328B1/en active Active
- 2012-11-20 JP JP2014542801A patent/JP6106182B2/ja active Active
- 2012-11-20 AU AU2012342562A patent/AU2012342562B2/en not_active Ceased
- 2012-11-20 CN CN201280057586.4A patent/CN103946214B/zh active Active
- 2012-11-20 MX MX2014006015A patent/MX2014006015A/es unknown
- 2012-11-20 IN IN4671CHN2014 patent/IN2014CN04671A/en unknown
- 2012-11-20 ES ES12791464.6T patent/ES2676068T3/es active Active
- 2012-11-20 WO PCT/EP2012/073125 patent/WO2013076090A1/en not_active Ceased
- 2012-11-20 US US14/358,537 patent/US9422243B2/en active Active
- 2012-11-20 CA CA2856759A patent/CA2856759A1/en not_active Abandoned
- 2012-11-20 EA EA201491026A patent/EA027800B1/ru not_active IP Right Cessation
- 2012-11-20 BR BR112014012031A patent/BR112014012031A2/pt not_active IP Right Cessation
- 2012-11-20 KR KR1020147017409A patent/KR20140097457A/ko not_active Withdrawn
-
2014
- 2014-05-20 CL CL2014001323A patent/CL2014001323A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| MX2014006015A (es) | 2014-06-04 |
| US9422243B2 (en) | 2016-08-23 |
| AU2012342562B2 (en) | 2017-02-23 |
| IN2014CN04671A (enExample) | 2015-09-18 |
| EP2788328A1 (en) | 2014-10-15 |
| HK1200166A1 (en) | 2015-07-31 |
| JP2014533709A (ja) | 2014-12-15 |
| CN103946214B (zh) | 2016-08-17 |
| CN103946214A (zh) | 2014-07-23 |
| EP2788328B1 (en) | 2018-01-31 |
| BR112014012031A2 (pt) | 2017-05-30 |
| WO2013076090A1 (en) | 2013-05-30 |
| EA027800B1 (ru) | 2017-09-29 |
| US20140336192A1 (en) | 2014-11-13 |
| ES2676068T3 (es) | 2018-07-16 |
| JP6106182B2 (ja) | 2017-03-29 |
| AU2012342562A1 (en) | 2014-07-10 |
| KR20140097457A (ko) | 2014-08-06 |
| EA201491026A1 (ru) | 2014-11-28 |
| CL2014001323A1 (es) | 2014-09-05 |
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| AU2012342562B2 (en) | 3-phenyl-isoquinolin-1(2H)-one derivatives as PARP-1 inhibitors | |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20181120 |