ES2544302T3 - Derivados de tetrahidroquinolina útiles como inhibidores de bromodominio - Google Patents
Derivados de tetrahidroquinolina útiles como inhibidores de bromodominio Download PDFInfo
- Publication number
- ES2544302T3 ES2544302T3 ES12716378.0T ES12716378T ES2544302T3 ES 2544302 T3 ES2544302 T3 ES 2544302T3 ES 12716378 T ES12716378 T ES 12716378T ES 2544302 T3 ES2544302 T3 ES 2544302T3
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- Prior art keywords
- methyl
- compound
- amino
- acetyl
- mmol
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- 102000001805 Bromodomains Human genes 0.000 title description 38
- 108050009021 Bromodomains Proteins 0.000 title description 36
- 239000003112 inhibitor Substances 0.000 title description 17
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 160
- 150000003839 salts Chemical class 0.000 claims abstract description 92
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 13
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical class 0.000 claims abstract description 7
- 125000001424 substituent group Chemical group 0.000 claims abstract description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 5
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000003373 pyrazinyl group Chemical group 0.000 claims abstract description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 3
- -1 5-cyanopyridin-2-yl Chemical group 0.000 claims description 94
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 239000008194 pharmaceutical composition Substances 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 26
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 14
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- 230000001363 autoimmune Effects 0.000 claims description 3
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
- C07D215/44—Nitrogen atoms attached in position 4 with aryl radicals attached to said nitrogen 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
- A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D401/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB201106743 | 2011-04-21 | ||
| GB201106743A GB201106743D0 (en) | 2011-04-21 | 2011-04-21 | Novel compounds |
| PCT/EP2012/057111 WO2012143413A1 (en) | 2011-04-21 | 2012-04-19 | Tetrahydroquinoline derivatives useful as bromodomain inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2544302T3 true ES2544302T3 (es) | 2015-08-28 |
Family
ID=44147335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES12716378.0T Active ES2544302T3 (es) | 2011-04-21 | 2012-04-19 | Derivados de tetrahidroquinolina útiles como inhibidores de bromodominio |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US9029395B2 (https=) |
| EP (1) | EP2699550B1 (https=) |
| JP (1) | JP5840763B2 (https=) |
| KR (1) | KR101896599B1 (https=) |
| CN (1) | CN103619820B (https=) |
| AU (1) | AU2012244759B2 (https=) |
| BR (1) | BR112013026834A2 (https=) |
| CA (1) | CA2832763C (https=) |
| EA (1) | EA022341B1 (https=) |
| ES (1) | ES2544302T3 (https=) |
| GB (1) | GB201106743D0 (https=) |
| IL (1) | IL228707A (https=) |
| MX (1) | MX338515B (https=) |
| SG (1) | SG194469A1 (https=) |
| WO (1) | WO2012143413A1 (https=) |
| ZA (1) | ZA201307645B (https=) |
Families Citing this family (30)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB201107325D0 (en) | 2011-05-04 | 2011-06-15 | Glaxosmithkline Llc | Novel compounds |
| US9073878B2 (en) | 2012-11-21 | 2015-07-07 | Zenith Epigenetics Corp. | Cyclic amines as bromodomain inhibitors |
| US9765039B2 (en) | 2012-11-21 | 2017-09-19 | Zenith Epigenetics Ltd. | Biaryl derivatives as bromodomain inhibitors |
| JP2016507496A (ja) | 2012-12-21 | 2016-03-10 | ゼニス・エピジェネティクス・コーポレイションＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｃｏｒｐ． | ブロモドメイン阻害剤としての新規複素環式化合物 |
| HUE043568T2 (hu) | 2013-03-14 | 2019-08-28 | Glaxosmithkline Ip No 2 Ltd | 2,3-diszubsztituált 1-acil-4-amino-1,2,3,4-tetrahidrokinolin származékok és bromodomén inhibitorokkénti felhasználásuk |
| SG11201506924YA (en) | 2013-03-15 | 2015-09-29 | Incyte Corp | Tricyclic heterocycles as bet protein inhibitors |
| JP6461118B2 (ja) | 2013-06-21 | 2019-01-30 | ゼニス・エピジェネティクス・リミテッドＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｌｔｄ． | ブロモドメイン阻害剤としての新規の置換された二環式化合物 |
| SI3010503T1 (sl) | 2013-06-21 | 2020-07-31 | Zenith Epigenetics Ltd. | Novi biciklični inhibitorji bromodomene |
| EP3019502B1 (en) | 2013-07-08 | 2017-05-17 | Incyte Holdings Corporation | Tricyclic heterocycles as bet protein inhibitors |
| JP6542212B2 (ja) | 2013-07-31 | 2019-07-10 | ゼニス・エピジェネティクス・リミテッドＺｅｎｉｔｈ Ｅｐｉｇｅｎｅｔｉｃｓ Ｌｔｄ． | ブロモドメイン阻害剤としての新規キナゾリノン |
| WO2015081189A1 (en) | 2013-11-26 | 2015-06-04 | Incyte Corporation | Bicyclic heterocycles as bet protein inhibitors |
| US9399640B2 (en) | 2013-11-26 | 2016-07-26 | Incyte Corporation | Substituted pyrrolo[2,3-c]pyridines and pyrazolo[3,4-c]pyridines as BET protein inhibitors |
| WO2015095492A1 (en) | 2013-12-19 | 2015-06-25 | Incyte Corporation | Tricyclic heterocycles as bet protein inhibitors |
| EP3105232B1 (en) | 2014-02-10 | 2019-08-28 | Concert Pharmaceuticals Inc. | Substituted triazolobenzodiazepines |
| PL3134403T3 (pl) | 2014-04-23 | 2020-07-13 | Incyte Corporation | 1H-pirolo[2,3-c]pirydyn-7(6H)-ony i pirazolo[3,4-c]pirydyn-7(6H)-ony jako inhibitory białek BET |
| JP6759514B2 (ja) | 2014-08-01 | 2020-09-23 | ヌエヴォリューション・アクティーゼルスカブＮｕｅｖｏｌｕｔｉｏｎ Ａ／Ｓ | ブロモドメインに対して活性な化合物 |
| BR112017004580A2 (pt) | 2014-09-12 | 2018-01-23 | GlaxoSmithKline Intellectual Property | composto, composição farmacêutica, produto de combinação, uso de um composto ou sal farmaceuticamente aceitável, e, método de tratamento. |
| JP6599979B2 (ja) | 2014-09-15 | 2019-10-30 | インサイト・コーポレイション | Ｂｅｔタンパク質阻害剤として用いるための三環式複素環化合物 |
| CA2960090A1 (en) * | 2014-10-02 | 2016-04-07 | Glaxosmithkline Intellectual Property (No.2) Limited | Compound |
| US10710992B2 (en) | 2014-12-01 | 2020-07-14 | Zenith Epigenetics Ltd. | Substituted pyridinones as bromodomain inhibitors |
| US10179125B2 (en) | 2014-12-01 | 2019-01-15 | Zenith Epigenetics Ltd. | Substituted pyridines as bromodomain inhibitors |
| WO2016092375A1 (en) | 2014-12-11 | 2016-06-16 | Zenith Epigenetics Corp. | Substituted heterocycles as bromodomain inhibitors |
| CA2966450A1 (en) | 2014-12-17 | 2016-06-23 | Olesya KHARENKO | Inhibitors of bromodomains |
| GB201504694D0 (en) | 2015-03-19 | 2015-05-06 | Glaxosmithkline Ip Dev Ltd | Covalent conjugates |
| WO2016203335A1 (en) | 2015-06-18 | 2016-12-22 | Pfizer Inc. | Novel pyrido[2,3-b]pyrazinones as bet-family bromodomain inhibitors |
| WO2017075377A1 (en) | 2015-10-29 | 2017-05-04 | Incyte Corporation | Amorphous solid form of a bet protein inhibitor |
| CA3028689A1 (en) | 2016-06-20 | 2017-12-28 | Incyte Corporation | Crystalline solid forms of a bet inhibitor |
| US10918647B2 (en) | 2016-07-26 | 2021-02-16 | University Of Southern California | Selective bromodomain inhibition of fungal Bdf1 |
| WO2018111805A1 (en) | 2016-12-13 | 2018-06-21 | St. Jude Children's Research Hospital | Tetrahydroquinoline-based bromodomain inhibitors |
| US11833155B2 (en) | 2020-06-03 | 2023-12-05 | Incyte Corporation | Combination therapy for treatment of myeloproliferative neoplasms |
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| GB9004781D0 (en) | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| CN1901958B (zh) | 2003-11-03 | 2011-03-09 | 葛兰素集团有限公司 | 流体分配装置 |
| JP2008156311A (ja) | 2006-12-26 | 2008-07-10 | Institute Of Physical & Chemical Research | Ｂｒｄ２ブロモドメイン結合剤 |
| KR101600634B1 (ko) | 2007-12-28 | 2016-03-07 | 미쓰비시 타나베 파마 코퍼레이션 | 항암제 |
| WO2010113498A1 (ja) * | 2009-03-31 | 2010-10-07 | 興和株式会社 | テトラヒドロキノリン化合物を有効成分とする貧血の予防及び／又は治療剤 |
| GB0919431D0 (en) | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| GB0919432D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Use |
| WO2011054851A1 (en) * | 2009-11-05 | 2011-05-12 | Glaxosmithkline Llc | Novel process |
| GB0919434D0 (en) * | 2009-11-05 | 2009-12-23 | Glaxosmithkline Llc | Novel compounds |
| GB201106750D0 (en) * | 2011-04-21 | 2011-06-01 | Glaxosmithkline Llc | Novel compounds |
| GB201107325D0 (en) * | 2011-05-04 | 2011-06-15 | Glaxosmithkline Llc | Novel compounds |
| WO2013033268A2 (en) * | 2011-08-29 | 2013-03-07 | Coferon, Inc. | Bivalent bromodomain ligands, and methods of using same |
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| CA2832763A1 (en) | 2012-10-26 |
| KR20140025484A (ko) | 2014-03-04 |
| EA022341B1 (ru) | 2015-12-30 |
| EP2699550B1 (en) | 2015-06-10 |
| SG194469A1 (en) | 2013-12-30 |
| AU2012244759A1 (en) | 2013-10-31 |
| CN103619820A (zh) | 2014-03-05 |
| GB201106743D0 (en) | 2011-06-01 |
| JP5840763B2 (ja) | 2016-01-06 |
| CN103619820B (zh) | 2015-08-19 |
| US9029395B2 (en) | 2015-05-12 |
| EA201391285A1 (ru) | 2014-04-30 |
| IL228707A0 (en) | 2013-12-31 |
| BR112013026834A2 (pt) | 2016-12-27 |
| US20140039006A1 (en) | 2014-02-06 |
| EP2699550A1 (en) | 2014-02-26 |
| JP2014511891A (ja) | 2014-05-19 |
| IL228707A (en) | 2016-09-29 |
| MX2013012190A (es) | 2014-01-31 |
| CA2832763C (en) | 2019-09-24 |
| WO2012143413A1 (en) | 2012-10-26 |
| AU2012244759B2 (en) | 2016-03-03 |
| ZA201307645B (en) | 2015-04-29 |
| MX338515B (es) | 2016-04-20 |
| KR101896599B1 (ko) | 2018-09-07 |
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