PE20231312A1 - Derivados triciclicos de carboxamida como inhibidores de la prmt5 - Google Patents

Derivados triciclicos de carboxamida como inhibidores de la prmt5

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Publication number
PE20231312A1
PE20231312A1 PE2023001721A PE2023001721A PE20231312A1 PE 20231312 A1 PE20231312 A1 PE 20231312A1 PE 2023001721 A PE2023001721 A PE 2023001721A PE 2023001721 A PE2023001721 A PE 2023001721A PE 20231312 A1 PE20231312 A1 PE 20231312A1
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PE
Peru
Prior art keywords
optionally substituted
independently selected
case
alkyl
compounds
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Application number
PE2023001721A
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English (en)
Inventor
Albert Amegadzie
Diane Jennifer Beylkin
Shon Booker
Matthew Paul Bourbeau
John R Butler
Sanne Omholt Schroder Glad
Todd J Kohn
Brian Alan Lanman
Kexue Li
Qingyian Liu
Patricia Lopez
Francesco Manoni
Primali Vasundera Navaratne
Liping H Pettus
Rene Rahimoff
Nuria A Tamayo
Mikkel Vestergaard
Hui-Ling Wang
Nicholas Anthony Weires
Original Assignee
Amgen Inc
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Application filed by Amgen Inc filed Critical Amgen Inc
Publication of PE20231312A1 publication Critical patent/PE20231312A1/es

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/02Heterocyclic 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
    • C07D491/04Ortho-condensed systems
    • C07D491/044Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
    • C07D491/048Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D471/00Heterocyclic 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
    • C07D471/02Heterocyclic 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
    • C07D471/04Ortho-condensed systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/50Pyridazines; Hydrogenated pyridazines
    • A61K31/501Pyridazines; Hydrogenated pyridazines not condensed and containing further heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • 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
    • 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
    • C07D471/00Heterocyclic 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
    • C07D471/12Heterocyclic 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 three hetero rings
    • C07D471/14Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic 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
    • C07D487/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D491/00Heterocyclic 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
    • C07D491/12Heterocyclic 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 three hetero rings
    • C07D491/14Ortho-condensed systems
    • C07D491/147Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D495/00Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04Ortho-condensed systems
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D519/00Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Referido a un compuesto de Formula I, un tautomero del mismo, un esteroisomero del mismo o una sal farmaceuticamente aceptable de cualquiera de los anteriores, en donde: R es un triciclo independientemente seleccionado de las formulas IA y IB, en donde la linea punteada es un enlace sencillo o doble; X1, X2, X6 y X7 son en cada caso N o C, en donde tanto X1 como X2 no pueden ser N al mismo tiempo, y en donde si X1 es C, puede estar opcionalmente sustituido con halo; X3, X4 y X5 se seleccionan en cada caso independientemente de un C, O, N y S opcionalmente sustituidos; R3 en cada caso se selecciona independientemente de H o alquilo C1-3; Ar1 es un arilo o heteroarilo opcionalmente sustituido de seis miembros; R1 en cada caso se selecciona independientemente de H, halo, alquilo C1-3 opcionalmente sustituido; entre otros; R2 en cada caso se selecciona independientemente de un alquilo C1-8 opcionalmente sustituido, ciclo o heterociclo de 5 o 6 miembros opcionalmente sustituido con hidroxi, amino, entre otros. Un compuesto seleccionado es 4-amino-N-(ciclopropilmetil)-N-((5-(trifluorometil)-2-piridinil)metil)-1,3-dihidrofuro[3,4-c]quinolin-8-carboxamida. Estos compuestos son derivados triciclicos de carboxamida, y son inhibidores de la PRMT5. Tambien se refiere a metodos de sintesis de dichos compuestos, productos intermedios, composiciones farmaceuticas que comprenden dichos compuestos, y su uso en el tratamiento de trastornos proliferativos, tales como cancer, trastornos metabolicos y sanguineos.
PE2023001721A 2020-11-24 2021-11-22 Derivados triciclicos de carboxamida como inhibidores de la prmt5 PE20231312A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202063117937P 2020-11-24 2020-11-24
PCT/US2021/060332 WO2022115377A1 (en) 2020-11-24 2021-11-22 Tricyclic carboxamide derivatives as prmt5 inhibitors

Publications (1)

Publication Number Publication Date
PE20231312A1 true PE20231312A1 (es) 2023-08-24

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PE2023001721A PE20231312A1 (es) 2020-11-24 2021-11-22 Derivados triciclicos de carboxamida como inhibidores de la prmt5

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US (1) US20240101570A1 (es)
EP (1) EP4251624A1 (es)
JP (1) JP2023550466A (es)
KR (1) KR20230113339A (es)
CN (1) CN116783191A (es)
AU (1) AU2021386149A1 (es)
CA (1) CA3202141A1 (es)
CL (1) CL2023001461A1 (es)
CO (1) CO2023007504A2 (es)
CR (1) CR20230286A (es)
IL (1) IL302820A (es)
MX (1) MX2023006145A (es)
PE (1) PE20231312A1 (es)
WO (1) WO2022115377A1 (es)

Families Citing this family (16)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11077101B1 (en) 2018-07-18 2021-08-03 Tango Therapeutics, Inc. Compounds and methods of use
EP4188920A1 (en) 2020-07-31 2023-06-07 Tango Therapeutics, Inc. Piperidin-1-yl-n-pyrydine-3-yl-2-oxoacetamide derivatives useful for the treatment of mtap-deficient and/or mta-accumulating cancers
CN116462677A (zh) * 2022-01-20 2023-07-21 上海和誉生物医药科技有限公司 一种多稠环prmt5抑制剂及其制备方法和应用
WO2023246873A1 (zh) * 2022-06-23 2023-12-28 南京明德新药研发有限公司 氨基取代的杂芳基衍生物及其应用
WO2024002377A1 (zh) * 2022-07-01 2024-01-04 上海赛岚生物科技有限公司 一类prmt5抑制剂及其用途
CN117362304A (zh) * 2022-07-07 2024-01-09 深圳微芯生物科技股份有限公司 一种甲酰胺取代的杂三环类衍生物、其制备方法及其应用
WO2024027370A1 (zh) * 2022-08-03 2024-02-08 上海和誉生物医药科技有限公司 一种含氮三稠环prmt5抑制剂,其制备方法和药学上的用途
WO2024038004A1 (en) 2022-08-15 2024-02-22 Astrazeneca Ab Mta-cooperative prmt5 inhibitors for use in the treatment of cancer
US20240254118A1 (en) * 2022-12-22 2024-08-01 Gilead Sciences, Inc. Prmt5 inhibitors and uses thereof
WO2024131901A1 (zh) * 2022-12-23 2024-06-27 深圳微芯生物科技股份有限公司 一类含炔基取代的杂环酰胺衍生物、其制备方法及其应用
WO2024153128A1 (en) * 2023-01-18 2024-07-25 Shanghai Antengene Corporation Limited Prmt5 inhibiting compounds and uses thereof
WO2024170488A1 (en) 2023-02-13 2024-08-22 Astrazeneca Ab Prmt5 inhibitor for use in cancer therapy
WO2024199255A1 (en) * 2023-03-30 2024-10-03 Beigene Switzerland Gmbh 5-AMINO-6, 8-DIHYDRO-1H-FURO [3, 4-d] PYRROLO [3, 2-b] PYRIDINE-2-CARBOXAMIDE DERIVATIVES AS MTA-COOPERATIVE INHIBITORS OF PRMT5
CN118221682A (zh) * 2023-05-17 2024-06-21 四川科伦博泰生物医药股份有限公司 酰胺化合物、包含其的药物组合物及其制备方法和用途
US11858935B1 (en) 2023-09-06 2024-01-02 King Faisal University Pyrrolo[2,3-c][1,7]naphthyridine-2-carboxylic acid compounds as CK2 inhibitors
US11891394B1 (en) 2023-09-06 2024-02-06 King Faisal University Pyrrolo[2,3-c][1,6]naphthyridine-8-carboxylic acid compounds as CK2 inhibitors

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WO2022115377A1 (en) 2022-06-02
CN116783191A (zh) 2023-09-19
CO2023007504A2 (es) 2023-09-08
EP4251624A1 (en) 2023-10-04
MX2023006145A (es) 2023-06-06
KR20230113339A (ko) 2023-07-28
AU2021386149A1 (en) 2023-06-22
AU2021386149A9 (en) 2024-08-08
CL2023001461A1 (es) 2023-12-01
IL302820A (en) 2023-07-01
US20240101570A1 (en) 2024-03-28
CR20230286A (es) 2023-08-24
CA3202141A1 (en) 2022-06-02
JP2023550466A (ja) 2023-12-01

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