PE20211475A1 - Inhibidores de kif18a - Google Patents

Inhibidores de kif18a

Info

Publication number
PE20211475A1
PE20211475A1 PE2021000930A PE2021000930A PE20211475A1 PE 20211475 A1 PE20211475 A1 PE 20211475A1 PE 2021000930 A PE2021000930 A PE 2021000930A PE 2021000930 A PE2021000930 A PE 2021000930A PE 20211475 A1 PE20211475 A1 PE 20211475A1
Authority
PE
Peru
Prior art keywords
alk
halo
haloalk
substituted
group
Prior art date
Application number
PE2021000930A
Other languages
English (en)
Inventor
Nuria A Tamayo
Liping H Pettus
Mary Catherine Walton
Ana Elena Minatti
Matthew Pau Bourbeau
Lei Jia
Abhisek Banerjee
James Alexander Brown
Michael J Frohn
Jian Jeffrey Chen
Kexue Li
Qingyian Liu
Jonathan Dante Low
Original Assignee
Amgen Inc
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 Amgen Inc filed Critical Amgen Inc
Publication of PE20211475A1 publication Critical patent/PE20211475A1/es

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Classifications

    • 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
    • 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
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • 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
    • A61P35/02—Antineoplastic agents specific for leukemia
    • 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
    • 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
    • C07D413/14—Heterocyclic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D419/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
    • C07D419/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms containing three or more hetero rings
    • 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
    • C07D491/10—Spiro-condensed systems
    • C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring

Abstract

Compuestos de formula (I), donde: X1 es N o -CR6 ; R1 es -CN, o un grupo -Z-R12 en el que Z es -NR11 -, -NR11SO2-, entre otros; R2 es halo o un grupo -Y-R13, en el que Y es -alc C0-4-, -N(alc C0-1)-alc C0-4-, entre otros; R3 es H, alc C1-4, o haloalc C1-4; R4 es H, halo, R4a o R4b; R5 es H, halo, alc C1-8, o haloalc C1-4; R6 es H, halo, alc C1-8, haloalc C1-4, entre otros; R7 es H, halo, alc C1-8, o haloalc C1-4; R8 es H, halo, alc C1-8, haloalc C1-4, entre otros; R9 es H, halo, alc C1-8, o haloalc C1-4; Rx es a), b), c) o d); cada uno de R10a, R10b, R10c, R10d, R10e, R10f, R10g, R10h, R10i, y R10j es H, halo, R10k, o R10l; R11 es H, R11a, o R11b; R12 es H, R12a, o R12b; R13 es R13a o R13b; R4a, R10k, R11a, R12a, y R13a es un anillo monociclico de 3, 4, 5, 6 o 7 miembros saturado, parcialmente saturado o insaturado, entre otros; R4b, R8b, R10l, R11b, R12b, y R13b son alc C1-6 sustituido por 0, 1, 2, 3, 4, o 5 grupo(s) seleccionado(s) entre F, Cl, Br, -ORa , -Ohaloalc C1-4, o CN; Ra es H o Rb ; y Rb es alc C1-6, fenilo o bencilo, en el que el alc C1-6 esta siendo sustituido por 0, 1, 2 o 3 sustituyentes seleccionados entre halo, - OH, -alc OC1-4, -NH2, -NHalc C1-4, -OC(=O)alc C1-4, o -N(alc C1-4)alc C1-4; y el fenilo o bencilo esta siendo sustituido por 0, 1, 2 o 3 sustituyentes seleccionados entre halo, alc C1-4, haloalc C1-3, -OH, -Oalc C1-4, -NH2, entre otros. Dichos compuestos modulan la proteina KIF18A alterando de esta forma el proceso del ciclo celular y la proliferacion celular para tratar el cancer y enfermedades relacionadas con cancer. La invencion tambien incluye composiciones farmaceuticas, que incluyen los compuestos, y metodos para tratar patologias relacionadas con la actividad de KIF18A.
PE2021000930A 2018-12-20 2019-12-20 Inhibidores de kif18a PE20211475A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201862783061P 2018-12-20 2018-12-20
PCT/US2019/068169 WO2020132648A1 (en) 2018-12-20 2019-12-20 Kif18a inhibitors

Publications (1)

Publication Number Publication Date
PE20211475A1 true PE20211475A1 (es) 2021-08-05

Family

ID=69187977

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2021000930A PE20211475A1 (es) 2018-12-20 2019-12-20 Inhibidores de kif18a

Country Status (22)

Country Link
US (2) US11236069B2 (es)
EP (1) EP3897852A1 (es)
JP (1) JP7407196B2 (es)
KR (1) KR20210106474A (es)
CN (1) CN113226473A (es)
AR (1) AR117490A1 (es)
AU (1) AU2019403486A1 (es)
BR (1) BR112021011989A2 (es)
CA (1) CA3123871A1 (es)
CL (1) CL2021001634A1 (es)
CO (1) CO2021008224A2 (es)
CR (1) CR20210387A (es)
EA (1) EA202191730A1 (es)
IL (1) IL283639B1 (es)
JO (1) JOP20210154B1 (es)
MA (1) MA54543A (es)
MX (1) MX2021007156A (es)
PE (1) PE20211475A1 (es)
SG (1) SG11202106520VA (es)
TW (1) TW202034924A (es)
UY (1) UY38526A (es)
WO (1) WO2020132648A1 (es)

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CA3123871A1 (en) * 2018-12-20 2020-06-25 Amgen Inc. Kif18a inhibitors
US20230151432A1 (en) * 2020-04-14 2023-05-18 Amgen Inc. Kif18a inhibitors for treatment of neoplastic diseases
CA3199082A1 (en) 2020-10-27 2022-05-05 Amgen Inc. Heterocyclic spiro compounds and methods of use
CA3217830A1 (en) 2021-04-29 2022-11-03 Amgen Inc. 2-aminobenzothiazole compounds and methods of use thereof
KR20240040742A (ko) 2021-06-25 2024-03-28 항저우 인노게이트 파마 컴퍼니 리미티드 Kif18a 억제제로서의 화합물
TW202321213A (zh) 2021-07-21 2023-06-01 美商安進公司 Ｋｉｆ１８ａ抑制劑化合物之鹽和固態形式
WO2023028564A1 (en) * 2021-08-26 2023-03-02 Volastra Therapeutics, Inc. Spiro indoline inhibitors of kif18a
WO2023088441A1 (zh) * 2021-11-19 2023-05-25 微境生物医药科技(上海)有限公司 Kif18a抑制剂
WO2023146973A1 (en) * 2022-01-26 2023-08-03 Amgen Inc. Synthesis of a kif18a inhibitor
WO2023159086A1 (en) 2022-02-16 2023-08-24 Amgen Inc. Quinazoline compounds and use thereof as inhibtors of mutant kras proteins
WO2023159087A1 (en) 2022-02-16 2023-08-24 Amgen Inc. Quinazoline compounds and use thereof as inhibtors of mutant kras proteins
WO2023174175A1 (zh) * 2022-03-17 2023-09-21 微境生物医药科技(上海)有限公司 Kif18a抑制剂
TW202345802A (zh) * 2022-04-15 2023-12-01 大陸商武漢人福創新藥物研發中心有限公司 Kif18a抑制劑及其用途
WO2023217232A1 (zh) * 2022-05-13 2023-11-16 上海湃隆生物科技有限公司 驱动蛋白kif18a抑制剂及其应用
WO2024002328A1 (zh) * 2022-06-30 2024-01-04 勤浩医药（苏州）有限公司 一种含氮化合物及其应用
WO2024032661A1 (zh) * 2022-08-11 2024-02-15 山东轩竹医药科技有限公司 Kif18a抑制剂及其用途
WO2024035950A1 (en) * 2022-08-12 2024-02-15 Accent Therapeutics, Inc. Inhibitors of kif18a and uses thereof
WO2024039829A1 (en) * 2022-08-18 2024-02-22 Accent Therapeutics, Inc. Inhibitors of kif18a and uses thereof
WO2024051755A1 (zh) * 2022-09-08 2024-03-14 长春金赛药业有限责任公司 Kif18a抑制剂化合物、药物组合物及其制备方法和应用
WO2024051812A1 (zh) * 2022-09-09 2024-03-14 先声再明医药有限公司 酰胺类化合物、其组合物及用途
WO2024067675A1 (zh) * 2022-09-30 2024-04-04 长春金赛药业有限责任公司 稠环类kif18a抑制剂化合物、药物组合物及其制备方法和应用
WO2024067465A1 (zh) * 2022-09-30 2024-04-04 山东轩竹医药科技有限公司 Kif18a抑制剂
CN115594664B (zh) * 2022-11-25 2023-02-24 英矽智能科技(上海)有限公司 一类螺环衍生物作为kif18a抑制剂
CN115947717B (zh) * 2023-03-09 2023-05-30 英矽智能科技(上海)有限公司 一类kif18a抑制剂

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