HRP20191186T1 - Derivati benzimidazola kao inhibitori bromodomene - Google Patents

Derivati benzimidazola kao inhibitori bromodomene Download PDF

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HRP20191186T1
HRP20191186T1 HRP20191186TT HRP20191186T HRP20191186T1 HR P20191186 T1 HRP20191186 T1 HR P20191186T1 HR P20191186T T HRP20191186T T HR P20191186TT HR P20191186 T HRP20191186 T HR P20191186T HR P20191186 T1 HRP20191186 T1 HR P20191186T1
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methyl
oxo
dimethyl
amino
dihydropyridin
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HRP20191186TT
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Rino Antonio Bit
John Alexander Brown
Philip G. HUMPHREYS
Katherine Louise Jones
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Glaxosmithkline Intellectual Property Development Limited
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    • 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
    • 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
    • C07D401/04—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 directly linked by a ring-member-to-ring-member bond
    • 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
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
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  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Epidemiology (AREA)

Claims (20)

1. Spoj formule (I), ili njegova sol: , naznačen time što svaki od R1 i R2 je neovisno vodik ili metil, uz uvjet da je najmanje jedan od R1 i R2 metil; R3 je C1-6alkil, C1-6alkoksi, cikloalkil, heterocikloalkil ili -CHR5(CH2)aR6; R4 je vezan na položaj 5 ili 6 u benzimidazolu i predstavlja ; R5 je vodik, C1-3alkil, C1-3alkoksi ili -(CH2)dOR9; R6 je vodik, C1-3alkil, C1-3alkoksi, -(CH2)eOR10, hidroksil, -NR11R12, halogen, cikloalkil, heterocikloalkil, aril ili heteroaril, gdje navedeni C1-3alkil, C1-3alkoksi, -(CH2)eOR10, cikloalkil, heterocikloalkil, aril ili heteroaril može biti izborno supstitiran s jednim ili dva supstituenta, koje se neovisno bira iz skupine koju čine C1-3alkil, C1-3alkoksi, halogen, -CH2OH, -COOH, te -COCH3; R7 je vodik, C1-6alkil, -(CH2)gcikloalkil, -(CH2)hheterocikloalkil, ili -CR13R14R15; R8 je vodik, C1-6alkil, cikloalkil, heterocikloalkil ili -CHR16R17, gdje je navedeni C1-6alkil izborno supstitiran s C1-3alkoksi, te gdje je R16 vodik ili C1-3alkil, a R17 je cikloalkil ili heterocikloalkil; svaki od R9, R10, R11, R12, R14, R15 i R18 je neovisno vodik ili C1-3alkil; R13 je vodik, hidroksil, -CH2OR18, halogen, -COOH, -CONH2, 1H-imidazol-4-il, -SH, -SeH, C1-3alkil, C1-3alkoksi, fenil ili 4-hidroksifenil, gdje navedeni C1-3alkil ili C1-3alkoksi može biti izborno supstitiran s halogenom, hidroksilom, -NHC(=NH2)NH2, -NH2, -COOH, -CONH2 ili -SCH3; a je 0, 1, 2 ili 3; b je 0 ili 1; c je 1, 2 ili 3, uz uvjet da kada je b 1, c je 2 ili 3; svaki od d i e je neovisno 1 ili 2; i svaki od g i h je neovisno 0, 1 ili 2.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je svaki od R1 i R2 metil.
3. Spoj u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačen time što R3 predstavlja 5 ili 6-eročlani heterocikloalkil ili skupina -CHR5R6, gdje R5 predstavlja vodik ili C1-3alkil, a R6 predstavlja 5 ili 6-eročlani heterocikloalkil, gdje navedeni heterocikloalkil može biti izborno supstitiran s C1-3alkilom ili -COCH3.
4. Spoj u skladu s patentnim zahtjevom 3, naznačen time što je R6: .
5. Spoj u skladu s patentnim zahtjevom 3 ili 4, naznačen time što R5 je vodik.
6. Spoj u skladu s patentnim zahtjevom 1 ili 2, naznačen time što R3 je-CHR5(CH2)aR6, R5 je -(CH2)dOR9, a je 0 i R6 je -(CH2)eOR10.
7. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time što b je 0, a c je 1.
8. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time što R4 predstavlja: .
9. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačen time što R7 je vodik, metil, izopropil, sec-butil, izobutil, -CH2-fenil, -CH2-4-hidroksifenil, -CH2OH, -CH(CH3)OH, -CH2SH, -CH2SeH,-(CH2)2SCH3, -CH2COOH, -(CH2)2COOH, -CH2CONH2, -(CH2)2CONH2, -(CH2)4NH2,-(CH2)3NHC(=NH2)NH2 ili -CH2-1H-imidazol-4-il.
10. Spoj u skladu s patentnim zahtjevom 9, naznačen time što R7 je -CH(CH3)OH.
11. Spoj u skladu s patentnim zahtjevom 8, naznačen time što R8 je izopropil, izobutil ili ciklopentil.
12. Spoj u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine: tert-butil-(2S,3R)-2-{[(1-{[(3R)-1-acetilpiperidin-3-il]metil}-2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1H-1,3-benzodiazol-6-il)metil]amino}-3-hidroksibutanoat; tert-butil-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-6-il]metil}amino)-3-hidroksibutanoat; 2-metilpropil-(2S)-2-[(2-{[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-5-il]oksi}etil)amino]-3-hidroksibutanoat; 2-metilpropil-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-[(3S)-oksan-3-ilmetil]-1H-1,3-benzodiazol-5-il]metil}amino)-3-hidroksibutanoat; tert-butil-(2S,3R)-2-{[(1-{[(3R)-1-acetilpiperidin-3-il]metil}-2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1H-1,3-benzodiazol-5-il)metil]amino}-3-hidroksibutanoat; propan-2-il-(2S,3R)-2-{[(1-{[(3R)-1-acetilpiperidin-3-il]metil}-2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1H-1,3-benzodiazol-5-il)metil]amino}-3-hidroksibutanoat; 2-metilpropil-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-3-ilmetil)-1H-1,3-benzodiazol-5-il]metil}amino)-3-hidroksibutanoat; ciclopentil-(2S)-2-[(2-{[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-5-il]oksi}etil)amino]propanoat; propan-2-il-(2S)-2-[(2-{[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-5-il]oksi}etil)amino]-3-hidroksibutanoat; propan-2-il-(2S,3R)-2-{[(1-{[(3R)-1-acetilpiperidin-3-il]metil}-2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1H-1,3-benzodiazol-6-il)metil]amino}-3-hidroksibutanoat; propan-2-il-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-[(3R)-oksan-3-ilmetil]-1H-1,3-benzodiazol-6-il]metil}amino)-3-hidroksibutanoat; ciclobutil-(2S,3R)-2-{[(1-{[(3R)-1-acetilpiperidin-3-il]metil}-2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1H-1,3-benzodiazol-5-il)metil]amino}-3-hidroksibutanoat; propan-2-il-(2S)-2-{[(1-{[(3R)-1-acetilpiperidin-3-il]metil}-2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1H-1,3-benzodiazol-5-il)metil]amino}-3-metilbutanoat; ciclopentil-(2S)-2-[(2-{[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-5-il]oksi}etil)amino]-3-metoksipropanoat; 2,2-dimetilpropil(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-6-il]metil}amino)-3-hidroksibutanoat; propan-2-il-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-[(3R)-oksan-3-ilmetil]-1H-1,3-benzodiazol-5-il]metil}amino)- 3-hidroksibutanoat; ciclobutil-(2S,3R)-2-[(2-{[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-5-il]oksi}etil)amino]-3-hidroksibutanoat; ciclopentil-(2S)-2-[(2-{[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-6-il]oksi}etil)amino]propanoat; propan-2-il-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-3-ilmetil)-1H-1,3-benzodiazol-5-il]metil}amino)-3-hidroksibutanoat; propan-2-il-(2S,3R)-2-{[(1-{[(3S)-1-acetilpiperidin-3-il]metil}-2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1H-1,3-benzodiazol-6-il)metil]amino}-3-hidroksibutanoat; propan-2-il-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-[(3R)-oksan-3-ilmetil]-1H-1,3-benzodiazol-6-il]metil}amino)-3-hidroksibutanoat; propan-2-il-(2S,3R)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-[(3R)-oksan-3-ilmetil]-1H-1,3-benzodiazol-5-il]metil}amino)-3-hidroksibutanoat; ciclobutil-(2R,3S)-2-({[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-[(3R)-oksan-3-ilmetil]-1H-1,3-benzodiazol-6-il]metil}amino)-3-hidroksibutanoat; i (3S)-oksolan-3-il-(2S,3R)-2-[(2-{[2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-(oksan-4-ilmetil)-1H-1,3-benzodiazol-5-il]oksi}etil)amino]-3-hidroksibutanoat, ili njezina sol.
13. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je (2S,3R)-izopropil-2-(((2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-((tetrahidro-2H-piran-4-il)metil)-1H-benzo[d]imidazol-5-il)metil)amino)-3-hidroksibutanoat, formule: , ili njegova sol.
14. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je (2S,3R)-2-(((2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-((tetrahidro-2H-piran-4-il)metil)-1H-benzo[d]imidazol-5-il)metil)amino)-3-hidroksibutanska kiselina, formule: , ili njezina sol.
15. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 14, naznačen time što je u obliku farmaceutski prihvatljive soli.
16. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je sol (2S,3R)-izopropil-2-(((2-(1,5-dimetil-6-okso-1,6-dihidropiridin-3-il)-1-((tetrahidro-2H-piran-4-il)metil)-1H-benzo[d]imidazol-5-il)metil)amino)-3-hidroksibutanoata s 1,2-etandisulfonskom kiselinom, formule: .
17. Spoj u skladu s patentnim zahtjevom 16, koji je u uglavnom kristalnom obliku i naznačen time što ima značajne signali difrakcije rendgenskih zraka na prahu (XRPD) u vrijednostima 2θ ± 0,1° 2θ kao eksperimentalna greška, od 5,4, 8,8, 9,9, 11,6, 13,8, 16,9, 18,0, 16,6, 19,1, 19,4, 19,8, 20,4, 20,9, 21,3, 22,0, 22,4, 22,9, 23,4, 24,9, te 25,1 stupnjeva.
18. Farmaceutski pripravak, naznačen time što sadrži spoj u skladu bilo kojim od patentnih zahtjeva 1 do 17, kao i jednu ili više farmaceutski prihvatljivih pomoćnih tvari.
19. Spoj u skladu bilo kojim od patentnih zahtjeva 1 do 17, naznačen time što je namijenjen upotrebi u terapiji.
20. Spoj u skladu bilo kojim od patentnih zahtjeva 1 do 17, naznačen time što je namijenjen upotrebi u liječenju reumatoidnog artritisa.
HRP20191186TT 2015-03-19 2019-07-01 Derivati benzimidazola kao inhibitori bromodomene HRP20191186T1 (hr)

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GBGB1504689.9A GB201504689D0 (en) 2015-03-19 2015-03-19 Chemical compounds
PCT/EP2016/055792 WO2016146738A1 (en) 2015-03-19 2016-03-17 Benzimidazole derivatives as bromodomain inhibitors
EP16710214.4A EP3271349B1 (en) 2015-03-19 2016-03-17 Benzimidazole derivatives as bromodomain inhibitors

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Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB201504689D0 (en) * 2015-03-19 2015-05-06 Glaxosmithkline Ip Dev Ltd Chemical compounds
CN108290856A (zh) 2015-08-11 2018-07-17 尼奥迈德研究所 芳基-取代的二氢喹诺酮、它们的制备和它们作为药物的用途
US10836742B2 (en) 2015-08-11 2020-11-17 Neomed Institute N-substituted bicyclic lactams, their preparation and their use as pharmaceuticals
IL257340B2 (en) 2015-08-12 2023-10-01 Neomed Inst Converted benzaimidazoles, methods for their preparation and use as pharmaceuticals
WO2017066876A1 (en) 2015-10-21 2017-04-27 Neomed Institute Substituted imidazopyridines, their preparation and their use as pharmaceuticals
WO2017127930A1 (en) 2016-01-28 2017-08-03 Neomed Institute Substituted [1,2,4]triazolo[4,3-a]pyridines, their preparation and their use as pharmaceuticals
GB201614934D0 (en) * 2016-09-02 2016-10-19 Glaxosmithkline Intellectual Property (No 2) Ltd Chemical compounds
GB201614940D0 (en) * 2016-09-02 2016-10-19 Glaxosmithkline Intellectual Property (No 2) Ltd Chemical compounds
GB201614939D0 (en) * 2016-09-02 2016-10-19 Glaxosmithkline Ip Dev Ltd Crystalline hydrate
EP3612522A4 (en) 2017-04-18 2021-07-07 Celgene Quanticel Research, Inc. THERAPEUTIC COMPOUNDS
CN109280046B (zh) * 2017-07-21 2021-02-02 浙江海正药业股份有限公司 苯并咪唑类衍生物及其制备方法及其在医药上的用途
EP3750885A4 (en) * 2018-02-06 2021-10-27 Shanghai Haihe Pharmaceutical Co., Ltd. COMPOUND PRESENTING AN INHIBITORING ACTIVITY OF BET, ITS PREPARATION PROCESS AND ITS USE
CN109369432B (zh) * 2018-11-02 2021-06-25 永农生物科学有限公司 (s)-4-氯-2-氨基丁酸酯的制备方法
JP2022053557A (ja) * 2019-02-08 2022-04-06 マルホ株式会社 ピリドン誘導体
WO2020190780A1 (en) * 2019-03-15 2020-09-24 Forma Therapeutics, Inc. Inhibiting cyclic amp-responsive element-binding protein (creb)
AU2020264106A1 (en) * 2019-04-24 2021-12-23 Convergene, Llc Small molecule bromodomain inhibitors and uses thereof
US20220227709A1 (en) * 2019-04-29 2022-07-21 The Board Of Regents Of The University Of Texas System Compositions and methods for treating schistosoma infections

Family Cites Families (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9004781D0 (en) 1990-03-02 1990-04-25 Glaxo Group Ltd Device
GB0201677D0 (en) 2002-01-25 2002-03-13 Glaxo Group Ltd Medicament dispenser
GB0515584D0 (en) 2005-07-28 2005-09-07 Glaxo Group Ltd Medicament dispenser
AR058289A1 (es) 2005-12-12 2008-01-30 Glaxo Group Ltd Colector para ser usado en dispensador de medicamento
KR101054325B1 (ko) 2006-03-31 2011-08-04 얀센 파마슈티카 엔.브이. 히스타민 ｈ４ 수용체 조절제로서의 벤조이미다졸―２―일 피리미딘 및 피라진
EP2493310A4 (en) * 2009-10-27 2014-03-12 Glaxosmithkline Llc BENZIMIDAZOLES AS INHIBITORS OF ACID GRAS SYNTHASE
GB0919434D0 (en) 2009-11-05 2009-12-23 Glaxosmithkline Llc Novel compounds
GB0919423D0 (en) 2009-11-05 2009-12-23 Glaxosmithkline Llc Novel compounds
MY170236A (en) 2010-10-06 2019-07-11 Glaxosmithkline Llc Benzimidazole derivatives as pi3 kinase inhibitors
GB201114103D0 (en) * 2011-08-17 2011-09-28 Glaxosmithkline Llc Novel compounds
WO2013097052A1 (en) * 2011-12-30 2013-07-04 Abbott Laboratories Bromodomain inhibitors
CA2895905A1 (en) * 2012-12-21 2014-06-26 Zenith Epigenetics Corp. Novel heterocyclic compounds as bromodomain inhibitors
KR102244719B1 (ko) 2013-03-15 2021-04-26 플렉시콘 인코퍼레이티드 헤테로시클릭 화합물 및 그의 용도
TWI530499B (zh) 2013-03-28 2016-04-21 吉李德科學股份有限公司 作為溴結構域（ｂｒｏｍｏｄｏｍａｉｎ）抑制劑之苯並咪唑酮衍生物類
TWI527811B (zh) * 2013-05-09 2016-04-01 吉李德科學股份有限公司 作爲溴結構域抑制劑的苯並咪唑衍生物
US9662311B2 (en) * 2013-06-21 2017-05-30 Zenith Epigenetics Ltd. Substituted bicyclic compounds as bromodomain inhibitors
US20150051208A1 (en) * 2013-08-14 2015-02-19 Boehringer Ingelheim International Gmbh Pyridinones
US9428515B2 (en) * 2014-05-09 2016-08-30 Boehringer Ingelheim International Gmbh Benzimidazole derivatives
GB201504689D0 (en) * 2015-03-19 2015-05-06 Glaxosmithkline Ip Dev Ltd Chemical compounds
GB201504694D0 (en) * 2015-03-19 2015-05-06 Glaxosmithkline Ip Dev Ltd Covalent conjugates
GB201614939D0 (en) * 2016-09-02 2016-10-19 Glaxosmithkline Ip Dev Ltd Crystalline hydrate

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