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
Application number
PCT/US2011/061954
Other languages
French (fr)
Other versions
WO2012071469A2 (en
Inventor
Hui Zhang
Tao Ye
Junmin Quan
Jing Wang
Original Assignee
Nevada Cancer Institute
Shenzhen Graduate School Of Peking University
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 Nevada Cancer Institute, Shenzhen Graduate School Of Peking University filed Critical Nevada Cancer Institute
Publication of WO2012071469A2 publication Critical patent/WO2012071469A2/en
Publication of WO2012071469A3 publication Critical patent/WO2012071469A3/en

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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
    • 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

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  • 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 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

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Family Applications (1)

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PCT/US2011/061954 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
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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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CN104136020B (en) 2012-02-27 2018-08-28 不列颠哥伦比亚癌症局分支机构 Effect protein interaction is reprogrammed to correct the epigenetic defect in cancer
MD20150043A2 (en) 2012-10-02 2015-08-31 Epitherapeutics Aps Inhibitors of histone demethylases
EP3170811A1 (en) * 2013-02-27 2017-05-24 Gilead Sciences, Inc. Ethyl pyridine-4-carboxylate compound as inhibitor of histone demethylases
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
AU2014306149B2 (en) 2013-08-06 2019-09-19 Imago Biosciences Inc. KDM1A inhibitors for the treatment of disease
US9527835B2 (en) 2014-02-13 2016-12-27 Incyte Corporation Cyclopropylamines as LSD1 inhibitors
AU2015217073B2 (en) 2014-02-13 2019-08-22 Incyte Holdings Corporation Cyclopropylamines as LSD1 inhibitors
WO2016007727A1 (en) 2014-07-10 2016-01-14 Incyte Corporation Triazolopyridines and triazolopyrazines as lsd1 inhibitors
WO2016007736A1 (en) 2014-07-10 2016-01-14 Incyte Corporation Imidazopyrazines as lsd1 inhibitors
TWI687419B (en) 2014-07-10 2020-03-11 美商英塞特公司 Imidazopyridines and imidazopyrazines as LSD1 inhibitors
WO2016007722A1 (en) 2014-07-10 2016-01-14 Incyte Corporation Triazolopyridines and triazolopyrazines as lsd1 inhibitors
CN107074807A (en) 2014-08-27 2017-08-18 吉利德科学公司 Composition and method for inhibition of histone demethylase
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
CN107406414B (en) * 2015-01-09 2022-04-19 基因泰克公司 (piperidin-3-yl) (naphthalen-2-yl) methanone derivatives as inhibitors of histone demethylase KDM2B for the treatment of cancer
KR102626978B1 (en) 2015-02-12 2024-01-18 이마고 바이오사이언시즈 인코포레이티드 Kdm1a inhibitors for the treatment of disease
TWI714567B (en) 2015-04-03 2021-01-01 美商英塞特公司 Heterocyclic compounds as lsd1 inhibitors
MY189367A (en) 2015-08-12 2022-02-08 Incyte 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
WO2017114497A1 (en) 2015-12-30 2017-07-06 Novartis Ag Immune effector cell therapies with enhanced efficacy
EP3430015A1 (en) 2016-03-16 2019-01-23 Oryzon Genomics, S.A. Methods to determine kdm1a target engagement and chemoprobes useful therefor
EP3445339B1 (en) 2016-04-22 2023-08-23 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 preparing 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
CN110996949A (en) 2017-08-03 2020-04-10 奥瑞泽恩基因组学股份有限公司 Methods for treating behavioral changes
KR20210008064A (en) 2018-05-11 2021-01-20 이마고 바이오사이언시즈 인코포레이티드 KDM1A inhibitors for the treatment of diseases
CN108957004B (en) * 2018-07-09 2021-10-19 东南大学 Application of reagent for detecting expression levels of H3K9me2 and H3K36me3 in preparation of gastric cancer prognosis evaluation kit
US10968200B2 (en) 2018-08-31 2021-04-06 Incyte Corporation Salts of an LSD1 inhibitor and processes for preparing the same
CA3130638A1 (en) 2019-03-20 2020-09-24 Oryzon Genomics, S.A. Methods of treating borderline personality disorder
CN113631164A (en) 2019-03-20 2021-11-09 奥莱松基因组股份有限公司 Methods of treating attention deficit hyperactivity disorder using KDM1A inhibitors such as the compound varespita
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
JP2022546908A (en) 2019-07-05 2022-11-10 オリゾン・ゲノミクス・ソシエダッド・アノニマ 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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