CN111372927A - 作为组蛋白甲基转移酶抑制剂的三环化合物 - Google Patents

作为组蛋白甲基转移酶抑制剂的三环化合物 Download PDF

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Publication number
CN111372927A
CN111372927A CN201880064130.8A CN201880064130A CN111372927A CN 111372927 A CN111372927 A CN 111372927A CN 201880064130 A CN201880064130 A CN 201880064130A CN 111372927 A CN111372927 A CN 111372927A
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compound
alkyl
hydroxy
substituted
optionally substituted
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CN201880064130.8A
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English (en)
Chinese (zh)
Inventor
Z·李
M·余
Q.徐
M·赞卡内尔拉
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Global Blood Therapeutics Inc
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Global Blood Therapeutics Inc
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    • 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
    • C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
    • C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
    • C07D221/04—Ortho- or peri-condensed ring systems
    • C07D221/06—Ring systems of three rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
    • C07B59/002—Heterocyclic compounds
    • 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
    • C07D219/00—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems
    • C07D219/04—Heterocyclic compounds containing acridine or hydrogenated acridine ring systems 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 carbon atoms of the ring system
    • C07D219/08—Nitrogen atoms
    • C07D219/10—Nitrogen atoms attached in position 9
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
    • C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic 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
    • C07D487/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/04—Ortho-condensed systems
    • C07D491/056—Ortho-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring
    • 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
    • C07B2200/05—Isotopically modified compounds, e.g. labelled

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
CN201880064130.8A 2017-08-15 2018-08-13 作为组蛋白甲基转移酶抑制剂的三环化合物 Pending CN111372927A (zh)

Applications Claiming Priority (5)

Application Number Priority Date Filing Date Title
US201762545936P 2017-08-15 2017-08-15
US62/545,936 2017-08-15
US201862712864P 2018-07-31 2018-07-31
US62/712,864 2018-07-31
PCT/US2018/046541 WO2019036377A1 (en) 2017-08-15 2018-08-13 TRICYCLIC COMPOUNDS AS HISTONE INHIBITORS METHYLTRANSFERASES

Publications (1)

Publication Number Publication Date
CN111372927A true CN111372927A (zh) 2020-07-03

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CN201880064130.8A Pending CN111372927A (zh) 2017-08-15 2018-08-13 作为组蛋白甲基转移酶抑制剂的三环化合物

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US (1) US11661410B2 (enExample)
EP (1) EP3668863B1 (enExample)
JP (1) JP7267993B2 (enExample)
CN (1) CN111372927A (enExample)
BR (1) BR112020003073A2 (enExample)
ES (1) ES3016407T3 (enExample)
IL (1) IL272507A (enExample)
MX (1) MX2020001825A (enExample)
SA (1) SA520411303B1 (enExample)
SG (1) SG11202001090WA (enExample)
TW (1) TW201920136A (enExample)
WO (1) WO2019036377A1 (enExample)
ZA (1) ZA202001503B (enExample)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110621316B (zh) 2017-04-21 2024-01-26 Epizyme股份有限公司 用ehmt2抑制剂进行的组合疗法
WO2019036384A1 (en) 2017-08-15 2019-02-21 Global Blood Therapeutics, Inc. TRICYCLIC COMPOUNDS AS HISTONE INHIBITORS METHYLTRANSFERASES
CN118317958A (zh) * 2021-11-25 2024-07-09 上海济煜医药科技有限公司 三并环衍生物及其制备方法和应用

Citations (1)

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Publication number Priority date Publication date Assignee Title
US20150274660A1 (en) * 2014-03-28 2015-10-01 Abbvie Inc. INHIBITORS OF HISTONE METHYLTRANSFERASE G9a

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US4107288A (en) * 1974-09-18 1978-08-15 Pharmaceutical Society Of Victoria Injectable compositions, nanoparticles useful therein, and process of manufacturing same
US5145684A (en) 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
WO2015085229A1 (en) 2013-12-08 2015-06-11 Van Andel Research Institute Autophagy inhibitors
CN106536509B (zh) 2014-06-16 2020-06-09 基础应用医学研究基金会 作为组蛋白甲基转移酶和dna甲基转移酶的双重抑制剂的新型化合物
JP2019501904A (ja) 2015-12-14 2019-01-24 ファンダシオン パラ ラ インベスティガシオン メディカ アプリカダＦｕｎｄａｃｉｏｎ Ｐａｒａ Ｌａ Ｉｎｖｅｓｔｉｇａｓｉｏｎ Ｍｅｄｉｃａ Ａｐｌｉｃａｄａ Ｄｎａメチルトランスフェラーゼの阻害剤としての２，４，６，７−四置換キノリン化合物
US11254651B2 (en) 2016-02-17 2022-02-22 Global Blood Therapeutics, Inc. Histone methyltransferase inhibitors
WO2019036384A1 (en) 2017-08-15 2019-02-21 Global Blood Therapeutics, Inc. TRICYCLIC COMPOUNDS AS HISTONE INHIBITORS METHYLTRANSFERASES

Patent Citations (1)

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US20150274660A1 (en) * 2014-03-28 2015-10-01 Abbvie Inc. INHIBITORS OF HISTONE METHYLTRANSFERASE G9a

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DEL GIUDICE等: "Synthesis and cholinesterase inhibitory activity of 6-, 7-methoxy-(and hydroxy-) tacrine derivatives", 《FARMACO》 *
JIANHONG TANG等: "The Divergent Transformations of Aromatic o-Aminonitrile with Carbonyl Compound", 《JOURNAL OF HETEROCYCLIC CHEMISTRY》 *
SANCHEZ, ISABEL等: "Synthesis and biological evaluation of modified acridines: the effect of N- and O- substituent inthe nitrogenated ring on antitumor activity", 《EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY》 *
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EP3668863A1 (en) 2020-06-24
US11661410B2 (en) 2023-05-30
BR112020003073A2 (pt) 2020-08-25
ES3016407T3 (en) 2025-05-09
ZA202001503B (en) 2023-07-26
JP2020531423A (ja) 2020-11-05
SA520411303B1 (ar) 2023-12-27
IL272507A (en) 2020-03-31
TW201920136A (zh) 2019-06-01
SG11202001090WA (en) 2020-03-30
US20230002351A1 (en) 2023-01-05
WO2019036377A1 (en) 2019-02-21
MX2020001825A (es) 2020-03-20
EP3668863C0 (en) 2025-03-19
JP7267993B2 (ja) 2023-05-02
EP3668863B1 (en) 2025-03-19

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Application publication date: 20200703