CN103391939B - 作为表观遗传酶调节剂的经取代的嘌呤和7-氮杂嘌呤化合物 - Google Patents

作为表观遗传酶调节剂的经取代的嘌呤和7-氮杂嘌呤化合物 Download PDF

Info

Publication number
CN103391939B
CN103391939B CN201180066760.7A CN201180066760A CN103391939B CN 103391939 B CN103391939 B CN 103391939B CN 201180066760 A CN201180066760 A CN 201180066760A CN 103391939 B CN103391939 B CN 103391939B
Authority
CN
China
Prior art keywords
alkyl
compound
group
halogen
cancer
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.)
Expired - Fee Related
Application number
CN201180066760.7A
Other languages
English (en)
Chinese (zh)
Other versions
CN103391939A (zh
Inventor
E·J·奥拉瓦
R·切斯沃斯
K·W·孔特斯
V·M·瑞创
R·M·波洛克
S·R·戴格勒
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Epizyme Inc
Original Assignee
Epizyme Inc
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Epizyme Inc filed Critical Epizyme Inc
Publication of CN103391939A publication Critical patent/CN103391939A/zh
Application granted granted Critical
Publication of CN103391939B publication Critical patent/CN103391939B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • A61K31/7076Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines containing purines, e.g. adenosine, adenylic acid
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A61K31/52Purines, e.g. adenine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/706Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
    • A61K31/7064Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00Drugs for disorders of the cardiovascular system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D473/00Heterocyclic compounds containing purine ring systems
    • C07D473/26Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32Nitrogen atom
    • C07D473/34Nitrogen atom attached in position 6, e.g. adenine
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/14Pyrrolo-pyrimidine radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16Purine radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16Purine radicals
    • C07H19/167Purine radicals with ribosyl as the saccharide radical

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Genetics & Genomics (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Psychiatry (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hospice & Palliative Care (AREA)
  • Rheumatology (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Oncology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Saccharide Compounds (AREA)
CN201180066760.7A 2010-12-03 2011-12-02 作为表观遗传酶调节剂的经取代的嘌呤和7-氮杂嘌呤化合物 Expired - Fee Related CN103391939B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US41966110P 2010-12-03 2010-12-03
US61/419,661 2010-12-03
PCT/US2011/063044 WO2012075381A1 (en) 2010-12-03 2011-12-02 Substituted purine and 7 - deazapurine compounds as modulators of epigenetic enzymes

Publications (2)

Publication Number Publication Date
CN103391939A CN103391939A (zh) 2013-11-13
CN103391939B true CN103391939B (zh) 2016-03-09

Family

ID=45444712

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201180066760.7A Expired - Fee Related CN103391939B (zh) 2010-12-03 2011-12-02 作为表观遗传酶调节剂的经取代的嘌呤和7-氮杂嘌呤化合物

Country Status (18)

Country Link
US (5) US8580762B2 (https=)
EP (1) EP2646444B1 (https=)
JP (1) JP5931905B2 (https=)
KR (1) KR101923746B1 (https=)
CN (1) CN103391939B (https=)
AR (1) AR084408A1 (https=)
AU (1) AU2011336415B2 (https=)
BR (1) BR112013013659B8 (https=)
CA (1) CA2819648C (https=)
DK (1) DK2646444T3 (https=)
ES (1) ES2577027T3 (https=)
HR (1) HRP20160655T1 (https=)
IL (1) IL226651A (https=)
MX (1) MX2013006251A (https=)
RU (1) RU2606514C2 (https=)
SI (1) SI2646444T1 (https=)
TW (1) TWI537271B (https=)
WO (1) WO2012075381A1 (https=)

Families Citing this family (57)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2819734A1 (en) 2010-12-03 2012-06-07 Epizyme, Inc. Carbocycle-substituted purine and 7-deazapurine compounds
EP2646455A4 (en) 2010-12-03 2014-04-02 Epizyme Inc Modulators of histone methyltransferase, and methods of use thereof
WO2012075381A1 (en) * 2010-12-03 2012-06-07 Epizyme, Inc. Substituted purine and 7 - deazapurine compounds as modulators of epigenetic enzymes
US9145438B2 (en) 2010-12-03 2015-09-29 Epizyme, Inc. 7-deazapurine modulators of histone methyltransferase, and methods of use thereof
WO2013055397A1 (en) 2011-10-14 2013-04-18 Children's Medical Center Corporation Inhibition and enhancement of reprogramming by chromatin modifying enzymes
SG10201913554YA (en) 2011-12-22 2020-03-30 Alios Biopharma Inc Substituted nucleosides, nucleotides and analogs thereof
USRE48171E1 (en) 2012-03-21 2020-08-25 Janssen Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
US9441007B2 (en) 2012-03-21 2016-09-13 Alios Biopharma, Inc. Substituted nucleosides, nucleotides and analogs thereof
WO2014026198A1 (en) 2012-08-10 2014-02-13 Epizyme, Inc. Inhibitors of protein methyltransferase dot1l and methods of use thereof
US9597348B2 (en) * 2012-09-06 2017-03-21 Epizyme, Inc. Method of treating leukemia
CA2894220A1 (en) * 2012-12-21 2014-06-26 Epizyme, Inc. Dot1l inhibitors for use in the treatment of leukemia
GEP201606600B (en) 2013-02-22 2017-01-10 Pfizer Pyrrolo [2, 3 -d]pyrimidine derivatives as inhibitors of janus- related kinases (jak)
WO2014153172A1 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Pyrazole derivatives as prmt1 inhibitors and uses thereof
US9446064B2 (en) * 2013-03-14 2016-09-20 Epizyme, Inc. Combination therapy for treating cancer
EP2970137A1 (en) 2013-03-14 2016-01-20 Epizyme, Inc. Pyrazole derivatives as arginine methyltransferase inhibitors and uses thereof
JP2016517434A (ja) * 2013-03-14 2016-06-16 エピザイム,インコーポレイティド 癌を処置するための併用療法
WO2014153100A2 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
WO2014152261A1 (en) * 2013-03-14 2014-09-25 Epizyme, Inc. Substituted 7-deazapurine compounds
JP2016518336A (ja) 2013-03-14 2016-06-23 エピザイム,インコーポレイティド Prmt1阻害剤としてのピラゾール誘導体およびその使用
US9120757B2 (en) 2013-03-14 2015-09-01 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
KR102028793B1 (ko) 2013-03-14 2019-10-07 에피자임, 인코포레이티드 아르기닌 메틸기 전이효소 억제제 및 이의 용도
WO2014153208A1 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
WO2014153214A1 (en) 2013-03-14 2014-09-25 Epizyme, Inc. Arginine methyl transferase inhibtors and uses thereof
US9765035B2 (en) 2013-03-14 2017-09-19 Epizyme, Inc. Arginine methyltransferase inhibitors and uses thereof
EP2970135B1 (en) 2013-03-14 2018-07-18 Epizyme, Inc. Pyrazole derivatives as prmt1 inhibitors and uses thereof
JP2016517426A (ja) * 2013-03-15 2016-06-16 エピザイム,インコーポレイティド 置換プリン化合物の合成方法
WO2014152562A1 (en) * 2013-03-15 2014-09-25 Epizyme, Inc. Injectable formulations for treating cancer
US9688714B2 (en) 2013-07-03 2017-06-27 Epizyme, Inc. Substituted purine compounds
EP3027195B1 (en) * 2013-07-29 2019-02-06 Dana-Farber Cancer Institute, Inc. Dot1l probes
AU2014295980B2 (en) 2013-08-02 2020-08-27 Memorial Sloan-Kettering Cancer Center Methods for the detection and treatment of leukemias that are responsive to DOT1L inhibition
US10143704B2 (en) * 2013-11-13 2018-12-04 Epizyme, Inc. Methods for treating cancer
US20170198006A1 (en) * 2014-06-25 2017-07-13 Epizyme, Inc. Prmt5 inhibitors and uses thereof
WO2016024185A1 (en) 2014-08-12 2016-02-18 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine derivatives useful for inhibiting janus kinase
AU2015301746A1 (en) * 2014-08-13 2017-02-16 Celgene Corporation Combination therapy for treating cancer
US9458165B2 (en) 2014-08-27 2016-10-04 Dana-Farber Cancer Institute, Inc. DOT1L inhibitors
WO2016044649A1 (en) * 2014-09-17 2016-03-24 Epizyme, Inc. Injectable formulations for treating cancer
EP3193884A4 (en) * 2014-09-17 2018-06-20 Epizyme, Inc. Combination therapy for treating cancer
EP3200826B1 (en) * 2014-09-30 2021-04-21 Vecht-lifshitz, Susan Eve Pharmaceutical compositions for treating ebola virus disease
WO2016123626A1 (en) * 2015-01-30 2016-08-04 Epizyme, Inc. Combination therapy for treating cancer
US11453697B1 (en) 2015-08-13 2022-09-27 Merck Sharp & Dohme Llc Cyclic di-nucleotide compounds as sting agonists
US10869868B2 (en) 2016-01-26 2020-12-22 Memorial Sloan Kettering Cancer Center Targeting chromatin regulators inhibits leukemogenic gene expression in NPM1 mutant leukemia
ES3057783T3 (en) 2016-03-15 2026-03-04 Oryzon Genomics Sa Combinations of lsd1 inhibitors for use in the treatment of neoplastic diseases
CA3017408C (en) 2016-03-15 2025-08-19 Oryzon Genomics, S.A. LSD1 INHIBITOR COMBINATIONS FOR THE TREATMENT OF HEMATOLOGICAL MALIGNITIS
CN106432095B (zh) * 2016-09-09 2019-04-16 东南大学 匹莫苯丹关键中间体6-(3,4-二氨基苯基)-5-甲基-4,5-二氢哒嗪-3(2h)-酮的制备
WO2018175746A1 (en) 2017-03-24 2018-09-27 Kura Oncology, Inc. Methods for treating hematological malignancies and ewing's sarcoma
CN109748944B (zh) * 2017-11-03 2021-12-10 中国科学院上海药物研究所 5’-脱氧-5’-异丙基取代氨基核苷类化合物、其制备方法和用途
CN109748943A (zh) * 2017-11-03 2019-05-14 中国科学院上海药物研究所 2’-c-甲基取代核苷类化合物及其制备与用途
JP2021505583A (ja) * 2017-12-05 2021-02-18 エンジェクス ファーマシューティカル インコーポレイテッド Pmrt5阻害剤としての複素環式化合物
KR102118891B1 (ko) 2018-10-04 2020-06-04 성균관대학교산학협력단 매소니아노사이드 b를 유효성분으로 포함하는 혼합 직계성 백혈병 유전자 재배열 동반 백혈병 예방 및 치료용 약학적 조성물
CA3126141A1 (en) 2019-01-09 2020-07-16 Dana-Farber Cancer Institute, Inc. Dot1l degraders and uses thereof
BR112021017831A2 (pt) * 2019-03-11 2021-11-30 Collaborative Medicinal Dev Llc Derivados heteroaromáticos e aromáticos heterobicíclicos para o tratamento de distúrbios relacionados com ferroptose
CN110092804A (zh) * 2019-03-29 2019-08-06 广州盈升生物科技有限公司 一种含双环基团的嘌呤化合物及其制备方法
MA55556A (fr) 2019-04-02 2022-02-09 Aligos Therapeutics Inc Composés ciblant prmt5
CN113024620B (zh) * 2021-03-11 2023-02-28 沈阳药科大学 一种嘌呤衍生物及其制备方法和用途
WO2022271540A1 (en) * 2021-06-21 2022-12-29 Mayo Foundation For Medical Education And Research Inhibitors of dot1l
CA3226162A1 (en) 2021-07-09 2023-01-12 Plexium, Inc. Aryl compounds and pharmaceutical compositions that modulate ikzf2
US20240335438A1 (en) * 2021-07-19 2024-10-10 Dana-Farber Cancer Institute, Inc. Targeting dot1l and smarca4/2 for the treatment of mllr leukemia

Family Cites Families (41)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US5763263A (en) 1995-11-27 1998-06-09 Dehlinger; Peter J. Method and apparatus for producing position addressable combinatorial libraries
US20020127598A1 (en) 2000-03-27 2002-09-12 Wenqiang Zhou Solution-phase combinatorial library synthesis and pharmaceutically active compounds produced thereby
EP1138689A1 (en) 2000-03-28 2001-10-04 Roche Diagnostics GmbH N8- and C8-linked purine bases as universal nucleosides used for oligonucleotide hybridization
EP1138688A1 (en) 2000-03-28 2001-10-04 Roche Diagnostics GmbH N8- and C8- linked purine bases as universal nucleosides used for oligonucleotide hybridization
US6534651B2 (en) 2000-04-06 2003-03-18 Inotek Pharmaceuticals Corp. 7-Substituted isoindolinone inhibitors of inflammation and reperfusion injury and methods of use thereof
US20040043959A1 (en) 2002-03-04 2004-03-04 Bloom Laura A. Combination therapies for treating methylthioadenosine phosphorylase deficient cells
EP1556399A4 (en) * 2002-07-16 2007-09-26 Merck & Co Inc Nucleoside derivatives as inhibitors of RNA-dependent viral RNA polymerase
AU2002951247A0 (en) 2002-09-06 2002-09-19 Alchemia Limited Compounds that interact with kinases
EP1572097A4 (en) 2002-09-30 2010-02-17 Smithkline Beecham Corp NUCLEOSIDE DERIVATIVES FOR THE TREATMENT OF INFECTIONS WITH THE HEPATITIS C-VIRUS
GB0301450D0 (en) * 2003-01-22 2003-02-19 Medical Res Council Protein crystal structure
PL1697394T3 (pl) * 2003-12-19 2007-08-31 Hoffmann La Roche Inhibitory COMT
AU2005267706B2 (en) 2004-08-02 2011-12-08 University Of Virginia Patent Foundation 2-propynyl adenosine analogs with modified 5'-ribose groups having A2A agonist activity
US7576069B2 (en) 2004-08-02 2009-08-18 University Of Virginia Patent Foundation 2-polycyclic propynyl adenosine analogs having A2A agonist activity
US8058762B2 (en) * 2005-01-19 2011-11-15 Daikin Industries, Ltd. Rotor, axial gap type motor, method of driving motor, and compressor
WO2006078752A2 (en) 2005-01-21 2006-07-27 Methylgene, Inc. Inhibitors of dna methyltransferase
PT1848718E (pt) 2005-02-04 2012-10-11 Millennium Pharm Inc Inibidores de enzimas de activação e1
US20060235037A1 (en) 2005-04-15 2006-10-19 Purandare Ashok V Heterocyclic inhibitors of protein arginine methyl transferases
WO2006113615A2 (en) 2005-04-15 2006-10-26 Sloan-Kettering Institute For Cancer Research Anti-microbial agents and uses thereof
KR101450535B1 (ko) 2006-02-02 2014-10-14 밀레니엄 파머슈티컬스 인코퍼레이티드 E1 활성화 효소의 억제제
AU2006339445A1 (en) 2006-03-02 2007-09-07 Agency For Science, Technology And Research Methods for cancer therapy and stem cell modulation
GB0607953D0 (en) 2006-04-21 2006-05-31 Novartis Ag Organic compounds
US8188063B2 (en) 2006-06-19 2012-05-29 University Of Virginia Patent Foundation Use of adenosine A2A modulators to treat spinal cord injury
US20080132525A1 (en) 2006-12-04 2008-06-05 Methylgene Inc. Inhibitors of DNA Methyltransferase
US20080312160A1 (en) 2007-04-09 2008-12-18 Guerrant Richard L Method of treating enteritis, intestinal damage, and diarrhea from c. difficile with an a2a adenosine receptor agonist
CN101417967A (zh) 2007-10-26 2009-04-29 浙江海正药业股份有限公司 组蛋白去乙酰酶抑制剂、其组合物及其应用
CN101910150B (zh) 2007-11-05 2013-09-18 诺瓦提斯公司 作为cetp抑制剂、可用于治疗疾病如高脂血症或动脉硬化的4-苄基氨基-1-羧基酰基哌啶衍生物
CN101938904A (zh) 2008-01-09 2011-01-05 PGx健康有限责任公司 用a2ar激动剂鞘内治疗神经性疼痛
AR072906A1 (es) 2008-08-06 2010-09-29 Novartis Ag Nucleosidos modificados utiles como antivirales
JPWO2010027005A1 (ja) 2008-09-05 2012-02-02 壽製薬株式会社 置換アミン誘導体及びこれを有効成分とする医薬組成物
WO2010048149A2 (en) 2008-10-20 2010-04-29 Kalypsys, Inc. Heterocyclic modulators of gpr119 for treatment of disease
IN2012DN01983A (https=) * 2009-08-24 2015-07-24 Ascepion Pharmaceuticals Inc
WO2012075381A1 (en) * 2010-12-03 2012-06-07 Epizyme, Inc. Substituted purine and 7 - deazapurine compounds as modulators of epigenetic enzymes
EP2646455A4 (en) 2010-12-03 2014-04-02 Epizyme Inc Modulators of histone methyltransferase, and methods of use thereof
US9145438B2 (en) 2010-12-03 2015-09-29 Epizyme, Inc. 7-deazapurine modulators of histone methyltransferase, and methods of use thereof
CA2819734A1 (en) 2010-12-03 2012-06-07 Epizyme, Inc. Carbocycle-substituted purine and 7-deazapurine compounds
US9597348B2 (en) * 2012-09-06 2017-03-21 Epizyme, Inc. Method of treating leukemia
US9446064B2 (en) * 2013-03-14 2016-09-20 Epizyme, Inc. Combination therapy for treating cancer
JP2016517426A (ja) 2013-03-15 2016-06-16 エピザイム,インコーポレイティド 置換プリン化合物の合成方法
AU2014295980B2 (en) * 2013-08-02 2020-08-27 Memorial Sloan-Kettering Cancer Center Methods for the detection and treatment of leukemias that are responsive to DOT1L inhibition
US10143704B2 (en) * 2013-11-13 2018-12-04 Epizyme, Inc. Methods for treating cancer

Also Published As

Publication number Publication date
US20150366893A1 (en) 2015-12-24
TWI537271B (zh) 2016-06-11
CN103391939A (zh) 2013-11-13
EP2646444B1 (en) 2016-03-16
HK1189596A1 (zh) 2014-06-13
AR084408A1 (es) 2013-05-15
CA2819648A1 (en) 2012-06-07
BR112013013659B1 (pt) 2022-06-21
US20140051654A1 (en) 2014-02-20
US20180280422A1 (en) 2018-10-04
JP2013544846A (ja) 2013-12-19
US8580762B2 (en) 2013-11-12
EP2646444A1 (en) 2013-10-09
BR112013013659B8 (pt) 2024-02-27
MX2013006251A (es) 2013-10-01
BR112013013659A2 (pt) 2016-09-06
JP5931905B2 (ja) 2016-06-08
IL226651A (en) 2016-11-30
KR20130125379A (ko) 2013-11-18
RU2013130250A (ru) 2015-01-10
ES2577027T3 (es) 2016-07-12
US20210252035A1 (en) 2021-08-19
SI2646444T1 (sl) 2016-09-30
WO2012075381A1 (en) 2012-06-07
US9096634B2 (en) 2015-08-04
AU2011336415B2 (en) 2016-08-11
TW201307348A (zh) 2013-02-16
RU2606514C2 (ru) 2017-01-10
HRP20160655T1 (hr) 2016-09-23
US20120142625A1 (en) 2012-06-07
KR101923746B1 (ko) 2018-11-29
AU2011336415A1 (en) 2013-06-20
CA2819648C (en) 2018-05-01
DK2646444T3 (da) 2016-06-27

Similar Documents

Publication Publication Date Title
CN103391939B (zh) 作为表观遗传酶调节剂的经取代的嘌呤和7-氮杂嘌呤化合物
EP3517535B1 (en) Alkynyl-substituted heterocyclic compound, preparation method therefor and medical use thereof
EP3068785B1 (en) Substituted 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine derivatives as casein kinase 1 d/e inhibitors
EP2646441B1 (en) Carbocycle-substituted purine and 7-deazapurine compounds
JP2022523786A (ja) ピラジン誘導体およびshp2の阻害の際のその適用
JP7847123B2 (ja) 化合物、組成物及び方法
CN103339139A (zh) 组蛋白甲基转移酶的7-氮杂嘌呤调节剂及其使用方法
CN109743875A (zh) Menin-mll相互作用的抑制剂
JP2022176364A (ja) 複素環化合物
KR20240155367A (ko) 아미노피리딘 유도체 및 이의 선택적 alk-2 억제제로서의 용도
JP2023536891A (ja) 重症肺炎を治療するためのjak阻害剤化合物
TW202010500A (zh) 作為a2a受體拮抗劑的吡唑並三唑並嘧啶衍生物
EP3950693A1 (en) Thienoheterocyclic derivative, preparation method therefor and medical use thereof
CN111848678A (zh) 含磷类噻吩并嘧啶衍生物
JP2023502279A (ja) Cps1を阻害するためのピペラジン化合物
Fleuti Synthesis of novel hetero-fused 7-deazapurine nucleosides and nucleotides with potential biological activity or for modifications of DNA and RNA
HK40097124A (zh) 取代的哒嗪-3-甲酰胺化合物作为tyk2抑制剂
WO2014152261A1 (en) Substituted 7-deazapurine compounds
CN116745299A (zh) 噻吩并嘧啶衍生物
HK1189596B (en) Substituted purine and 7-deazapurine compounds as modulators of epigenetic enzymes

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
CF01 Termination of patent right due to non-payment of annual fee
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20160309