MX2021004624A - Derivados de 2-(2-acriloil-2,6-diazaspiro[3.4]octan-6-il)-6-(1h-in dazol-4-il)-benzonitrilo y compuestos relacionados como inhibidores de la proteina kras mutante g12c para inhibir metastasis de tumor. - Google Patents

Derivados de 2-(2-acriloil-2,6-diazaspiro[3.4]octan-6-il)-6-(1h-in dazol-4-il)-benzonitrilo y compuestos relacionados como inhibidores de la proteina kras mutante g12c para inhibir metastasis de tumor.

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Publication number
MX2021004624A
MX2021004624A MX2021004624A MX2021004624A MX2021004624A MX 2021004624 A MX2021004624 A MX 2021004624A MX 2021004624 A MX2021004624 A MX 2021004624A MX 2021004624 A MX2021004624 A MX 2021004624A MX 2021004624 A MX2021004624 A MX 2021004624A
Authority
MX
Mexico
Prior art keywords
diazaspiro
indazol
acryloyl
octan
inhibitors
Prior art date
Application number
MX2021004624A
Other languages
English (en)
Inventor
Yuan Liu
Pingda Ren
Yi Liu
Liansheng Li
Jun Feng
Tao Wu
Original Assignee
Araxes Pharma Llc
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 Araxes Pharma Llc filed Critical Araxes Pharma Llc
Publication of MX2021004624A publication Critical patent/MX2021004624A/es

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Classifications

    • 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
    • C07D487/10—Spiro-condensed systems
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/416—1,2-Diazoles condensed with carbocyclic ring systems, e.g. indazole
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/04—Antineoplastic agents specific for metastasis
    • 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
    • C07D471/10—Spiro-condensed systems

Abstract

La presente invención proporciona por ejemplo 2-(2-acriloil-2,6-diazaespiro[3.4]octan-6-il)-6-(1H-indazol-4-il) -benzonitrilo y por ejemplo derivados de 2-(2-acriloil-2,6-diazaes piro[3.4]octan-6-il)-6-(1H-indazol-4-il)-benzonitrilo y compuestos de la fórmula (I) relacionados como inhibidores de proteína KRAS mutante G12C para el tratamiento de la metástasis tumoral. La presente descripción describe compuestos ejemplares (por ejemplo, páginas 53 a 90; tabla 1; compuestos I-1 a I-141), datos farmacológicos (por ejemplo, páginas 125 a 128; tabla 2; ejemplo 1) y síntesis de los mismos (por ejemplo, páginas 129 a 143; ejemplos 2 a 7). Los compuestos ejemplares son por ejemplo 2-(2-acriloil-2,6-diazaespiro[3.4]octan-6-il)-6-(5-metil-1H-indaz ol-4-il)-4- morfolinobenzonitrilo (ejemplo 2; compuesto I-1) y 6-(2-acriloil-2,7-diazaespiro[3.5]nonan-7-il)-3-metoxi-2-(5-metil -1H-indazol-4-il)-4-morfolinobenzonitrilo (ejemplo 7; compuesto I-84).
MX2021004624A 2018-10-24 2019-10-23 Derivados de 2-(2-acriloil-2,6-diazaspiro[3.4]octan-6-il)-6-(1h-in dazol-4-il)-benzonitrilo y compuestos relacionados como inhibidores de la proteina kras mutante g12c para inhibir metastasis de tumor. MX2021004624A (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862750009P 2018-10-24 2018-10-24
PCT/US2019/057694 WO2020086739A1 (en) 2018-10-24 2019-10-23 2-(2-acryloyl-2,6-diazaspiro[3.4]octan-6-yl)-6-(1h-indazol-4-yl)-benzonitrile derivatives and related compounds as inhibitors of g12c mutant kras protein for inhibiting tumor metastasis

Publications (1)

Publication Number Publication Date
MX2021004624A true MX2021004624A (es) 2021-05-27

Family

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Family Applications (1)

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MX2021004624A MX2021004624A (es) 2018-10-24 2019-10-23 Derivados de 2-(2-acriloil-2,6-diazaspiro[3.4]octan-6-il)-6-(1h-in dazol-4-il)-benzonitrilo y compuestos relacionados como inhibidores de la proteina kras mutante g12c para inhibir metastasis de tumor.

Country Status (10)

Country Link
US (1) US20210380595A1 (es)
EP (1) EP3870585A1 (es)
JP (1) JP2022505835A (es)
KR (1) KR20210083286A (es)
CN (1) CN113207291A (es)
AU (1) AU2019364417A1 (es)
BR (1) BR112021007726A2 (es)
CA (1) CA3117210A1 (es)
MX (1) MX2021004624A (es)
WO (1) WO2020086739A1 (es)

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UY35464A (es) 2013-03-15 2014-10-31 Araxes Pharma Llc Inhibidores covalentes de kras g12c.
JO3805B1 (ar) 2013-10-10 2021-01-31 Araxes Pharma Llc مثبطات كراس جي12سي
TW201702232A (zh) 2015-04-10 2017-01-16 亞瑞克西斯製藥公司 經取代之喹唑啉化合物及其使用方法
US10875842B2 (en) 2015-09-28 2020-12-29 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
WO2017058728A1 (en) 2015-09-28 2017-04-06 Araxes Pharma Llc Inhibitors of kras g12c mutant proteins
US10975071B2 (en) 2015-09-28 2021-04-13 Araxes Pharma Llc Inhibitors of KRAS G12C mutant proteins
TW201726656A (zh) 2015-11-16 2017-08-01 亞瑞克西斯製藥公司 包含經取代雜環基團之２－經取代喹唑啉化合物及其使用方法
US11279689B2 (en) 2017-01-26 2022-03-22 Araxes Pharma Llc 1-(3-(6-(3-hydroxynaphthalen-1-yl)benzofuran-2-yl)azetidin-1 yl)prop-2-en-1-one derivatives and similar compounds as KRAS G12C modulators for treating cancer
US11274093B2 (en) 2017-01-26 2022-03-15 Araxes Pharma Llc Fused bicyclic benzoheteroaromatic compounds and methods of use thereof
EP3573970A1 (en) 2017-01-26 2019-12-04 Araxes Pharma LLC 1-(6-(3-hydroxynaphthalen-1-yl)quinazolin-2-yl)azetidin-1-yl)prop-2-en-1-one derivatives and similar compounds as kras g12c inhibitors for the treatment of cancer
JP7327802B2 (ja) 2017-01-26 2023-08-16 アラクセス ファーマ エルエルシー 縮合ヘテロ－ヘテロ二環式化合物およびその使用方法
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EP3870585A1 (en) 2021-09-01
BR112021007726A2 (pt) 2021-07-27
CN113207291A (zh) 2021-08-03
AU2019364417A1 (en) 2021-05-20
CA3117210A1 (en) 2020-04-30
KR20210083286A (ko) 2021-07-06
US20210380595A1 (en) 2021-12-09
JP2022505835A (ja) 2022-01-14
WO2020086739A1 (en) 2020-04-30

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