EA201990023A1 - SUBSTITUTED PYRIDINES AS DNMT1 INHIBITORS - Google Patents

SUBSTITUTED PYRIDINES AS DNMT1 INHIBITORS

Info

Publication number
EA201990023A1
EA201990023A1 EA201990023A EA201990023A EA201990023A1 EA 201990023 A1 EA201990023 A1 EA 201990023A1 EA 201990023 A EA201990023 A EA 201990023A EA 201990023 A EA201990023 A EA 201990023A EA 201990023 A1 EA201990023 A1 EA 201990023A1
Authority
EA
Eurasian Patent Office
Prior art keywords
dnmt1
relates
treatment
diseases associated
compound according
Prior art date
Application number
EA201990023A
Other languages
Russian (ru)
Other versions
EA038355B1 (en
Inventor
Николас Дэвид Адамс
Эндрю Б. Беновиц
Мария Лурдес Руэда Бенеде
Карен Андерсон Эванс
Дэвид Т. Фосбеннер
Брайан Уэйн Кинг
Мей ЛИ
Хуан Игнасио Луэнго
Уилльям Генри Миллер
Александр Джозеф Райф
Стюарт Пол Ромерил
Стэнли Дж. Шмидт
Роджер Дж. Батлин
Кристин М. Голдберг
Аллан М. Джордан
Кристофер С. Кершо
Али Рауф
Богдан Вашковыч
Original Assignee
Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед
Кэнсэр Ресерч Текнолоджи Лтд.
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 Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед, Кэнсэр Ресерч Текнолоджи Лтд. filed Critical Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед
Priority claimed from PCT/IB2017/053511 external-priority patent/WO2017216727A1/en
Publication of EA201990023A1 publication Critical patent/EA201990023A1/en
Publication of EA038355B1 publication Critical patent/EA038355B1/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
    • C07D213/72Nitrogen atoms
    • C07D213/73Unsubstituted amino or imino radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen 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
    • C07D213/72Nitrogen atoms
    • C07D213/74Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D413/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14Heterocyclic 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Изобретение относится к замещенным производным пиридина. В частности, изобретение относится к соединениям, соответствующим формуле (Iar)где Y, X, X, R, R, R, Rи Rопределены в описании изобретения; или их фармацевтически приемлемым солям или пролекарствам. Соединения по изобретению являются селективными ингибиторами DNMT1 и могут быть использованы при лечении злокачественного новообразования, предраковых симптомов, бета-гемоглобинопатий, серповидно-клеточного заболевания, серповидно-клеточной анемии и бета-талассемии и болезней, связанных с ингибированием DNMT1. Соответственно изобретение, кроме того, относится к фармацевтическим композициям, содержащим соединение по изобретению. Изобретение, более того, относится к способам ингибирования активности DNMT1 и лечения заболеваний, связанных с применением соединения по изобретению или фармацевтической композиции, содержащей соединение по изобретению.The invention relates to substituted pyridine derivatives. In particular, the invention relates to compounds corresponding to the formula (Iar) where Y, X, X, R, R, R, R and R are defined in the description of the invention; or their pharmaceutically acceptable salts or prodrugs. The compounds of the invention are selective inhibitors of DNMT1 and can be used in the treatment of malignant neoplasms, precancerous symptoms, beta hemoglobinopathies, sickle cell disease, sickle cell anemia and beta thalassemia and diseases associated with inhibition of DNMT1. Accordingly, the invention further relates to pharmaceutical compositions comprising a compound of the invention. The invention furthermore relates to methods of inhibiting the activity of DNMT1 and the treatment of diseases associated with the use of a compound according to the invention or a pharmaceutical composition comprising a compound according to the invention.

EA201990023A 2016-10-25 2017-06-13 Substituted pyridines as inhibitors of dnmt1 EA038355B1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662412343P 2016-10-25 2016-10-25
PCT/IB2017/053511 WO2017216727A1 (en) 2016-06-13 2017-06-13 Substituted pyridines as inhibitors of dnmt1

Publications (2)

Publication Number Publication Date
EA201990023A1 true EA201990023A1 (en) 2019-05-31
EA038355B1 EA038355B1 (en) 2021-08-12

Family

ID=66644945

Family Applications (1)

Application Number Title Priority Date Filing Date
EA201990023A EA038355B1 (en) 2016-10-25 2017-06-13 Substituted pyridines as inhibitors of dnmt1

Country Status (1)

Country Link
EA (1) EA038355B1 (en)

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR101146010B1 (en) * 2009-09-10 2012-05-16 서울대학교산학협력단 COMPOSITION FOR PREVENTING OR TREATING TNF-alpha MEDIATED DISEASES

Also Published As

Publication number Publication date
EA038355B1 (en) 2021-08-12

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