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AR095430A1 - Compuestos de pirimidina y piridina y su uso como inhibidores de la actividad de fgfr - Google Patents

Compuestos de pirimidina y piridina y su uso como inhibidores de la actividad de fgfr

Info

Publication number
AR095430A1
AR095430A1 ARP140100975A ARP140100975A AR095430A1 AR 095430 A1 AR095430 A1 AR 095430A1 AR P140100975 A ARP140100975 A AR P140100975A AR P140100975 A ARP140100975 A AR P140100975A AR 095430 A1 AR095430 A1 AR 095430A1
Authority
AR
Argentina
Prior art keywords
alkyl
optionally substituted
independently selected
heteroaryl
haloalkyl
Prior art date
Application number
ARP140100975A
Other languages
English (en)
Inventor
Su Wei
Guo - Zhang Weihan
Li Jinshui
Original Assignee
Hutchison Medipharma Ltd
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 Hutchison Medipharma Ltd filed Critical Hutchison Medipharma Ltd
Publication of AR095430A1 publication Critical patent/AR095430A1/es

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    • 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00Drugs for disorders of the endocrine system
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/32One oxygen, sulfur or nitrogen atom
    • C07D239/42One nitrogen atom
    • 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
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02Heterocyclic 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
    • C07D403/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D403/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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 two hetero rings
    • C07D405/06Heterocyclic 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 two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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 two hetero rings
    • C07D405/10Heterocyclic 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 two hetero rings linked by a carbon chain containing aromatic rings
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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 two hetero rings
    • C07D405/12Heterocyclic 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 two hetero rings linked by a chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/14Heterocyclic 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
    • 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
    • C07D413/02Heterocyclic 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
    • C07D413/12Heterocyclic 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
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Epidemiology (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Composiciones farmacéuticas que los contienen, y su uso en terapia de enfermedades que responden a inhibición de FGFR, por ejemplo, cáncer. Reivindicación 1: Un compuesto de fórmula (1) o una sal farmacéuticamente aceptable del mismo, en donde X es CH₂, Y es seleccionado de CH₂, O ó S(O)₂; ó X e Y junto con el enlace entre ellos forman -CH=CH- ó -CºC-; G es N ó CH; R¹ es arilo o heteroarilo, cada uno está opcionalmente sustituido con uno o más sustituyentes independientemente seleccionados de halo, -NR⁶R⁷, -OR⁸, -S(O)ₙR⁹, -(CH₂)ʳ-C(O)R¹⁰, -CN, -C(O)NR⁶R⁷, -NR⁶C(O)R¹⁰, -NR⁶S(O)ₙR⁹, -NR⁶S(O)ₙNR¹¹R¹², -NR⁶C(O)OR⁸, -NR⁶C(O)NR¹¹R¹², -NO₂, -S(O)ₙNR⁶R⁷, oxo, alquilo opcionalmente sustituido, -(CH₂)ₚ-cicloalquilo opcionalmente sustituido, -(CH₂)ₘ-heterociclilo opcionalmente sustituido, -(CH₂)q-heteroarilo opcionalmente sustituido, alquenilo opcionalmente sustituido, y alquinilo opcionalmente sustituido; R² es independientemente elegido de alquilo C₁₋₆ opcionalmente sustituido, alcoxi C₁₋₆ opcionalmente sustituido, o cicloalquilo C₃₋₈ opcionalmente sustituido; R³, R⁴ son elegidos independientemente de hidrógeno, halógeno, -CN, o alquilo C₁₋₆ opcionalmente sustituido; R⁵ es alquilo C₁₋₆, ó R³ y R⁵ junto con el átomo de O al cual R⁵ está unido y el enlace entre ellos forman un anillo heterocíclico que contiene oxígeno de 5 ó 6 miembros; n es 1 ó 2; m, p, q y r son elegidos independientemente de 0, 1, 2, 3, 4, 5, 6; R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹ y R¹² son independientemente seleccionados de hidrógeno, alquilo, cicloalquilo, arilo, heteroarilo, heterociclilo, cada uno de los cuales excepto el hidrógeno, está opcionalmente sustituido con uno o más sustituyentes independientemente seleccionados de halo, hidroxilo, mercapto, oxo, alquilo, cicloalquilo, heterociclilo, amino opcionalmente sustituido, y amida opcionalmente sustituida, en donde cada grupo opcionalmente sustituido anterior para los cuales el(los) sustituyente(s) no está(n) específicamente designado(s), pueden estar no sustituidos o independientemente sustituidos con uno o más, tal como uno, dos o tres, sustituyentes independientemente seleccionados de alquilo C₁₋₆, alquenilo C₂₋₆, alquinilo C₂₋₆, cicloalquilo, arilo, heterociclilo, heteroarilo, aril-alquil C₁₋₆-, heteroaril-alquil C₁₋₆-, haloalquil C₁₋₆-, -O-alquilo C₁₋₆, -O-alquenilo C₂₋₆, -O-alquil C₁₋₆fenilo, -alquil C₁₋₆-OH, -alquil C₁₋₆-SH, -alquil C₁₋₆-O-alquilo C₁₋₆, -O-haloalquilo C₁₋₆, halo, -OH, mercapto, -NH₂, -alquil C₁₋₆-NH₂, -N(alquilo C₁₋₆)₂, -NH(alquilo C₁₋₆), -N(alquilo C₁₋₆)(alquil C₁₋₆fenilo), -NH(alquil C₁₋₆fenilo), ciano, nitro, oxo, -C(O)-OH, -C(O)O-alquilo C₁₋₆, -CON(alquilo C₁₋₆)₂, -CONH(alquilo C₁₋₆), -CONH₂, -NHC(O)(alquilo C₁₋₆), -NHC(O)(fenilo), -N(alquilo C₁₋₆)C(O)(alquilo C₁₋₆), -N(alquilo C₁₋₆)C(O)(fenilo), -C(O)alquilo C₁₋₆, -C(O)alquil C₁₋₆fenilo, -C(O)haloalquilo C₁₋₆, -OC(O)alquilo C₁₋₆, -S(O)₂-alquilo C₁₋₆, -S(O)-alquilo C₁₋₆, -S(O)₂-fenilo, -S(O)₂-haloalquilo C₁₋₆, -S(O)₂NH₂, -S(O)₂NH(alquilo C₁₋₆), -S(O)₂NH(fenilo), -NHS(O)₂(alquilo C₁₋₆), -NHS(O)₂(fenilo), y -NHS(O)₂(haloalquilo C₁₋₆).
ARP140100975A 2013-03-15 2014-03-13 Compuestos de pirimidina y piridina y su uso como inhibidores de la actividad de fgfr AR095430A1 (es)

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PCT/CN2013/072690 WO2014139145A1 (en) 2013-03-15 2013-03-15 Novel pyrimidine and pyridine compounds and usage thereof

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US (2) US20160052926A1 (es)
EP (1) EP2970120B1 (es)
JP (1) JP6109969B2 (es)
KR (1) KR101697982B1 (es)
CN (1) CN105143185B (es)
AR (1) AR095430A1 (es)
AU (1) AU2014231437B2 (es)
BR (1) BR112015020772B1 (es)
CA (1) CA2900748C (es)
CL (1) CL2015002520A1 (es)
CY (1) CY1121804T1 (es)
DK (1) DK2970120T3 (es)
EA (1) EA028654B1 (es)
ES (1) ES2697697T3 (es)
HR (1) HRP20181906T1 (es)
IL (1) IL240790B (es)
LT (1) LT2970120T (es)
MX (1) MX363397B (es)
MY (1) MY192641A (es)
NZ (1) NZ711460A (es)
PE (1) PE20151601A1 (es)
PH (1) PH12015502047B1 (es)
PL (1) PL2970120T3 (es)
PT (1) PT2970120T (es)
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SG (1) SG11201506280SA (es)
SI (1) SI2970120T1 (es)
SM (1) SMT201800596T1 (es)
TW (1) TWI618698B (es)
UA (1) UA113470C2 (es)
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TW201439064A (zh) 2014-10-16
AU2014231437A1 (en) 2015-09-03
US9701680B2 (en) 2017-07-11
CY1121804T1 (el) 2020-07-31
BR112015020772B1 (pt) 2022-06-07
IL240790B (en) 2019-10-31
PH12015502047B1 (en) 2019-03-08
CN105143185B (zh) 2018-02-13
IL240790A0 (en) 2015-10-29
EP2970120A4 (en) 2016-08-31
JP2016510774A (ja) 2016-04-11
JP6109969B2 (ja) 2017-04-05
KR101697982B1 (ko) 2017-01-19
EP2970120A1 (en) 2016-01-20
NZ711460A (en) 2019-05-31
DK2970120T3 (en) 2018-12-10
EA201591301A1 (ru) 2016-03-31
ZA201505999B (en) 2017-11-29
WO2014139145A1 (en) 2014-09-18
HK1212687A1 (zh) 2016-06-17
TWI618698B (zh) 2018-03-21
LT2970120T (lt) 2019-01-10
US20160024021A1 (en) 2016-01-28
RS58136B1 (sr) 2019-02-28
PE20151601A1 (es) 2015-11-02
SG11201506280SA (en) 2015-09-29
CN105143185A (zh) 2015-12-09
SI2970120T1 (sl) 2019-02-28
PH12015502047A1 (en) 2016-01-18
AU2014231437B2 (en) 2016-11-17
PT2970120T (pt) 2018-11-27
MX363397B (es) 2019-03-21
SMT201800596T1 (it) 2019-01-11
UA113470C2 (xx) 2017-01-25
CL2015002520A1 (es) 2016-03-28
US20160052926A1 (en) 2016-02-25
EP2970120B1 (en) 2018-09-12
KR20150126391A (ko) 2015-11-11
CA2900748A1 (en) 2014-09-18
PL2970120T3 (pl) 2019-03-29
MY192641A (en) 2022-08-29
BR112015020772A2 (pt) 2017-07-18
WO2014139465A1 (en) 2014-09-18
CA2900748C (en) 2017-10-17
ES2697697T3 (es) 2019-01-25
MX2015012363A (es) 2016-02-03
HRP20181906T1 (hr) 2019-02-22
EA028654B1 (ru) 2017-12-29

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