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WO2012071469A3 - Histone demethylase inhibitors and uses thereof for treatment o f cancer - Google Patents

Histone demethylase inhibitors and uses thereof for treatment o f cancer Download PDF

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Publication number
WO2012071469A3
WO2012071469A3 PCT/US2011/061954 US2011061954W WO2012071469A3 WO 2012071469 A3 WO2012071469 A3 WO 2012071469A3 US 2011061954 W US2011061954 W US 2011061954W WO 2012071469 A3 WO2012071469 A3 WO 2012071469A3
Authority
WO
WIPO (PCT)
Prior art keywords
independently
sulfonamido
azido
alkylcarbonyl
heteroaryl
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.)
Ceased
Application number
PCT/US2011/061954
Other languages
French (fr)
Other versions
WO2012071469A2 (en
Inventor
Hui Zhang
Tao Ye
Junmin Quan
Jing Wang
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.)
Peking University Shenzhen Graduate School
Nevada Cancer Institute
Original Assignee
Peking University Shenzhen Graduate School
Nevada Cancer Institute
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 Peking University Shenzhen Graduate School, Nevada Cancer Institute filed Critical Peking University Shenzhen Graduate School
Publication of WO2012071469A2 publication Critical patent/WO2012071469A2/en
Publication of WO2012071469A3 publication Critical patent/WO2012071469A3/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
    • C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
    • C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/40—Oxygen atoms
    • C07D211/44—Oxygen atoms attached in position 4
    • C07D211/46—Oxygen atoms attached in position 4 having a hydrogen atom as the second substituent in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/56—Nitrogen atoms
    • C07D211/58—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
    • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

A compound of formula I: or a pharmaceutically acceptable salt, Ri is an optionally substituted heterocyclic group; R and R' are independently H, CH3, NO2, SO2N(CH3)2, SO2N((CH3)SO2), COOH, COOCH3, CO(N(CH3)), alkyl, alkenyl, alkynyl, aryl, aralkyl, cycloalkyl, heteroaryl, heterocycloalkyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, trifluoromethyl, pentafluoroethyl, halogen, cyano, thio, amido, ether, ester, hydroxyl, hydroxyalkyl, saturated or unsaturated fatty acids, azido, phosphonamido, sulfonamido, lactam, phosphate, phosphonato, phosphinato, amino, acylamino, amidino, imino, guanidino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, cyano, or azido; m and n are independently integers from 1 to 4; T, U, V, and Z are independently CH, N, or CR; L is NH, CH2, O, S, or SO2; X is N or CH; Y and Y' are independently O or S; and R3 is an optionally substituted aryl, heteroaryl, cycloalkyl, or heterocycloalkyl group.
PCT/US2011/061954 2010-11-23 2011-11-22 Histone demethylase inhibitors and uses thereof for treatment o f cancer Ceased WO2012071469A2 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US41656610P 2010-11-23 2010-11-23
US61/416,566 2010-11-23

Publications (2)

Publication Number Publication Date
WO2012071469A2 WO2012071469A2 (en) 2012-05-31
WO2012071469A3 true WO2012071469A3 (en) 2012-07-26

Family

ID=46146406

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/061954 Ceased WO2012071469A2 (en) 2010-11-23 2011-11-22 Histone demethylase inhibitors and uses thereof for treatment o f cancer

Country Status (1)

Country Link
WO (1) WO2012071469A2 (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9493442B2 (en) 2014-02-13 2016-11-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US9493450B2 (en) 2014-02-13 2016-11-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
CN107174584B (en) * 2016-03-12 2020-09-01 福建金乐医药科技有限公司 Application of piperazine structure-containing compound in preparation of LSD1 inhibitor

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2013225592B2 (en) 2012-02-27 2017-11-09 British Columbia Cancer Agency Branch Reprogramming effector protein interactions to correct epigenetic defects in cancer
PL3023415T3 (en) * 2012-10-02 2018-06-29 Gilead Sciences, Inc. Inhibitors of histone demethylases
BR112015020650A2 (en) 2013-02-27 2017-07-18 Epitherapeutics Aps histone demethylase inhibitors
CN103898206A (en) * 2013-05-13 2014-07-02 北京希普生国际生物医学研究院 Gene detection kit for prognostic evaluation of lung cancer, as well as preparation method and applications thereof
US9790195B2 (en) 2013-08-06 2017-10-17 Imago Biosciences, Inc. KDM1A inhibitors for the treatment of disease
US9527835B2 (en) 2014-02-13 2016-12-27 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
HUE046273T2 (en) 2014-02-13 2020-02-28 Incyte Corp Cyclopropylamines as LSD1 Inhibitors
WO2016007722A1 (en) 2014-07-10 2016-01-14 Incyte Corporation Triazolopyridines and triazolopyrazines as lsd1 inhibitors
WO2016007727A1 (en) 2014-07-10 2016-01-14 Incyte Corporation Triazolopyridines and triazolopyrazines as lsd1 inhibitors
TW201613925A (en) 2014-07-10 2016-04-16 Incyte Corp Imidazopyrazines as LSD1 inhibitors
WO2016007731A1 (en) 2014-07-10 2016-01-14 Incyte Corporation Imidazopyridines and imidazopyrazines as lsd1 inhibitors
BR112017003442A2 (en) 2014-08-27 2017-11-28 Gilead Sciences Inc compounds and methods for inhibiting histone demethylases
CN104262238B (en) * 2014-08-29 2016-08-03 西安交通大学 A kind of heteroaromatic biphenyl class Bcr-Abl inhibitor and its preparation method and application
WO2016112284A1 (en) * 2015-01-09 2016-07-14 Genentech, Inc. (piperidin-3-yl)(naphthalen-2-yl)methanone derivatives and related compounds as inhibitors of the histone demethylase kdm2b for the treatment of cancer
DK3256218T3 (en) 2015-02-12 2025-02-10 Imago Biosciences Inc KDM1A INHIBITORS AND THEIR USE IN THERAPY
CN107660205B (en) 2015-04-03 2021-08-27 因赛特公司 Heterocyclic compounds as LSD1 inhibitors
HUE070538T2 (en) 2015-08-12 2025-06-28 Incyte Holdings Corp Salts of an lsd1 inhibitor
WO2017099829A1 (en) 2015-12-11 2017-06-15 The General Hospital Corporation Compositions and methods for treating drug-tolerant glioblastoma
CA3009709A1 (en) 2015-12-30 2017-07-06 Novartis Ag Immune effector cell therapies with enhanced efficacy
EP3430015B9 (en) 2016-03-16 2025-12-31 Oryzon Genomics, S.A. METHOD FOR DETERMINING KDM1A TARGET ENGAGEMENT AND SUITABLE CHEMOPROBES FOR THIS PURPOSE
CA3021678A1 (en) 2016-04-22 2017-10-26 Incyte Corporation Formulations of an lsd1 inhibitor
CN111194306B (en) 2016-08-16 2023-05-16 伊美格生物科学公司 Methods and processes for the preparation of KDM1A inhibitors
WO2018083189A1 (en) * 2016-11-03 2018-05-11 Oryzon Genomics, S.A. Biomarkers for determining responsiveness to lsd1 inhibitors
WO2018106984A1 (en) 2016-12-09 2018-06-14 Constellation Pharmaceuticals, Inc. Markers for personalized cancer treatment with lsd1 inhibitors
WO2019025588A1 (en) 2017-08-03 2019-02-07 Oryzon Genomics, S.A. Methods of treating behavior alterations
EP3790867B1 (en) 2018-05-11 2024-03-27 Imago Biosciences Inc. Kdm1a inhibitors for the treatment of disease
CN108957004B (en) * 2018-07-09 2021-10-19 东南大学 Application of reagents for detecting the expression levels of H3K9me2 and H3K36me3 in the preparation of gastric cancer prognosis assessment kits
WO2020047198A1 (en) 2018-08-31 2020-03-05 Incyte Corporation Salts of an lsd1 inhibitor and processes for preparing the same
EP3941466B1 (en) 2019-03-20 2025-11-19 Oryzon Genomics, S.A. Vafidemstat for the treatment of non-aggressive symptoms of borderline personality disorder
RS67485B1 (en) 2019-03-20 2025-12-31 Oryzon Genomics Sa Methods of treating attention deficit hyperactivity disorder using kdm1a inhibitors such as the compound vafidemstat
CN110257320A (en) * 2019-06-11 2019-09-20 华夏源（上海）细胞基因工程股份有限公司 The induction of clinical grade iPS a kind of and screening technique
CN114341366A (en) 2019-07-05 2022-04-12 奥莱松基因组股份有限公司 Biomarkers and methods for personalized treatment of small cell lung cancer using KDM1A inhibitors

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5670505A (en) * 1993-11-29 1997-09-23 Fujisawa Pharmaceutical Co., Ltd. Piperazine derivatives
US20060292607A1 (en) * 2005-06-08 2006-12-28 Vanderbilt University Analysis of tissue samples surrounding malignancies
US20070208082A1 (en) * 2005-08-10 2007-09-06 John Hopkins University Polyamines useful as anti-parasitic and anti-cancer therapeutics and as lysine-specific demethylase inhibitors
US20070274912A1 (en) * 2003-09-16 2007-11-29 The Rocefeller University Histone Modifications as Binary Switches Controlling Gene Expression
US20090170796A1 (en) * 2004-12-16 2009-07-02 Yang Shi Histone Demethylation Mediated By The Nuclear Amine Oxidase Homolog LSD1

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5670505A (en) * 1993-11-29 1997-09-23 Fujisawa Pharmaceutical Co., Ltd. Piperazine derivatives
US20070274912A1 (en) * 2003-09-16 2007-11-29 The Rocefeller University Histone Modifications as Binary Switches Controlling Gene Expression
US20090170796A1 (en) * 2004-12-16 2009-07-02 Yang Shi Histone Demethylation Mediated By The Nuclear Amine Oxidase Homolog LSD1
US20060292607A1 (en) * 2005-06-08 2006-12-28 Vanderbilt University Analysis of tissue samples surrounding malignancies
US20070208082A1 (en) * 2005-08-10 2007-09-06 John Hopkins University Polyamines useful as anti-parasitic and anti-cancer therapeutics and as lysine-specific demethylase inhibitors

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9493442B2 (en) 2014-02-13 2016-11-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
US9493450B2 (en) 2014-02-13 2016-11-15 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
CN107174584B (en) * 2016-03-12 2020-09-01 福建金乐医药科技有限公司 Application of piperazine structure-containing compound in preparation of LSD1 inhibitor

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