HRP20211675T1 - Inhibitori kinaze pirazolil hinoksalina - Google Patents

Inhibitori kinaze pirazolil hinoksalina Download PDF

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HRP20211675T1
HRP20211675T1 HRP20211675TT HRP20211675T HRP20211675T1 HR P20211675 T1 HRP20211675 T1 HR P20211675T1 HR P20211675T T HRP20211675T T HR P20211675TT HR P20211675 T HRP20211675 T HR P20211675T HR P20211675 T1 HRP20211675 T1 HR P20211675T1
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Croatia
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6alkyl
substituted
alkyl
4alkyl
nr14r15
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HRP20211675TT
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Gordon Saxty
Christopher William Murray
Valerio Berdini
Gilbert Ebai Besong
Christopher Charles Frederick Hamlett
Christopher Norbert Johnson
Steven John Woodhead
Michael Reader
David Charles Rees
Laurence Anne Mevellec
Patrick René Angibaud
Eddy Jean Edgard Freyne
Tom Cornelis Hortense Govaerts
Johan Erwin Edmond Weerts
Timothy Pietro Suren Perera
Ronaldus Arnodus Hendrika Joseph Gilissen
Berthold Wroblowski
Jean Fernand Armand Lacrampe
Alexandra Papanikos
Olivier Alexis Georges Querolle
Elisabeth Thérèse Jeanne PASQUIER
Isabelle Noëlle Constance PILATTE
Pascal Ghislain André BONNET
Werner Constant Johan Embrechts
Rhalid Akkari
Lieven Meerpoel
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Astex Therapeutics Limited
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Claims (19)

1. Uporaba spoja formule (I) za proizvodnju lijeka za profilaksu ili liječenje raka kod pacijenta kojem je postavljena dijagnoza da formira dio sub-populacije koja posjeduje genetičku aberaciju FGFR3 kinaze, pri čemu, spoj formule (I) je: [image] uključujući bilo koji njihov tautomerni ili stereohemijski izomerni oblik, pri čemu n predstavlja cijeli broj koji je jednak 0, 1, 2, 3 ili 4; R1predstavlja vodik, C1-6alkil, C2-4alkenil, hidroksiC1-6alkil, haloC1-6alkil, hidroksihaloC1-6alkil, cijanoC1-4alkil, C1-6alkoksiC1-6alkil pri čemu je svaki C1-6alkil moguće izborno zamijeniti sa jednom ili dvije hidroksilne grupe, C1-6alkil supstituiran sa -NR4R5, C1-6alkil supstituiran sa -C(=O)-NR4R5, -S(=O)2-C1-6alkil, -S(=O)2-haloC1-6alkil, -S(=O)2-NR14R15, C1-6alkil supstituiran sa -S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -S(=O)2-NR14R15, C1-6alkil supstituiran sa -NH- S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NH-S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -NR12-S(=O)2-NR14R15, R6, C1-6alkil supstituiran sa R6, C1-6alkil supstituiran sa -C(=O)-R6, hidroksiC1-6alkil supstituiran sa R6, C1-6alkil supstituiran sa -Si(CH3)3, C1-6alkil supstituiran sa-P(=O)(OH)2 ili C1-6alkil supstituiran sa-P(=O)(OC1-6alkil)2; svaki R1a se neovisno bira iz vodika, C1-4alkil, hidroksiC1-4alkil, C1-4alkil supstituiran sa amino ili mono- ili di(C1-4alkil)amino ili -NH(C3-8cikloalkil), cijanoC1-4alkil, C1-4alkoksiC1-4alkil, i C1-4alkil supstituiran sa jednim ili više atoma fluora; svako R2 se neovisno bira iz atoma koji je hidroksil, halogen, cijano, C1-4alkil, C2-4alkenil, C2-4alkinil, C1-4alkoksi, hidroksiC1-4alkil, hidroksiC1-4alkoksi, haloC1-4alkil, haloC1-4alkoksi, hidroksihaloC1-4alkil, hidroksihaloC1-4alkoksi, C1-4alkoksiC1-4alkil, haloC1-4alkoksiC1-4alkil, C1-4alkoksiC1-4alkil pri čemu svaki C1-4alkil može izborno biti supstituiran sa jednom ili dvije hidroksil grupe, hidroksihaloC1-4alkoksiC1-4alkil, R13, C1-4alkil supstituiran sa R13, C1-4alkil supstituiran sa -C(=O)-R13, C1-4alkoksi supstituiran sa R13, C1-4alkoksi supstituiran sa -C(=O)-R13, -C(=O)-R13, C1-4alkil supstituiran sa -NR7R8, C1-4alkil supstituiran sa -C(=O)-NR7R8, C1-4alkoksi supstituiran sa -NR7R8, C1-4alkoksi supstituiran sa -C(=O)-NR7R8, -NR7R8 i - C(=O)-NR7R8; ili kada dvije R2 grupe se spoje na susjedne atome ugljika oni se mogu uzeti zajedno da formiraju radikal ili formulu: -O-(C(R17)2)p-O-; -X-CH=CH-; ili -X-CH=N-; pri čemu R17 predstavlja vodik ili fluor, p predstavlja 1 ili 2 i X predstavlja O ili S; R3 predstavlja hidroksil, C1-6alkoksi, hidroksiC1-6alkoksi, C1-6alkoksi supstituiran sa -NR10R11, C1-6alkil, C2-6alkenil, C2-6alkinil, haloC1-6alkil izborno supstituiran sa -O-C(=O)-C1-6alkil, hidroksiC1-6alkil izborno supstituiran sa -O-C(=O)-C1-6alkil, hidroksiC2-6alkenil, hidroksiC2-6alkinil, hidroksihaloC1-6alkil, cijanoC1-6alkil, C1-6alkil supstituiran sa karboksil, C1-6alkil supstituiran sa -C(=O)-C1-6alkil, C1-6alkil supstituiran sa -C(=O)-O-C1-6alkil, C1-6alkil supstituiran sa C1-6alkoksiC1-6alkil-O-C(=O)-, C1-6alkil supstituiran sa C1-6alkoksiC1-6alkil-C(=O)-, C1-6alkil supstituiran sa -O-C(=O)-C1-6alkil, C1-6alkoksiC1-6alkil hidro C1-6alkil može izborno biti supstituiran sa jednom ili dvije hidroksil grupe ili sa -O-C(=O)-C1-6alkil, C2-6alkenil supstituiran sa C1-6alkoksi, C2-6alkinil supstituiran sa C1-6alkoksi, C1-6alkil supstituiran sa R9 i izborno supstituiran sa -O-C(=O)-C1-6alkil, C1-6alkil supstituiran sa -C(=O)-R9, C1-6alkil supstituiran sa hidroksilom i R9, C2-6alkenil supstituiran sa R9, C2-6alkinil supstituiran sa R9, C1-6alkil supstituiran sa -NR10R11, C2-6alkenil supstituiran sa -NR10R11, C2-6alkinil supstituiran sa -NR10R11, C1-6alkil supstituiran sa hidroksil i -NR10R11, C1-6alkil supstituiran sa jednim ili dva halogena i -NR10R11, -C1-6alkil-C(R12)=N-O-R12, C1-6alkil supstituiran sa -C(=O)-NR10R11, C1-6alkil supstituiran sa -O-C(=O)-NR10R11, -S(=O)2-C1-6alkil, -S(=O)2-haloC1-6alkil, -S(=O)2-NR14R15, C1-6alkil supstituiran sa -S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -S(=O)2-NR14R15, C1-6alkil supstituiran sa -NR12-S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NH-S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -NR12-S(=O)2-NR14R15, R13, C1-6alkil supstituiran sa -P(=O)(OH)2 ili C1-6alkil supstituiran sa -P(=O)(OC1-6alkil)2; R4 i R5 svaki neovisno predstavlja vodik, C1-6alkil, hidroksiC1-6alkil, haloC1-6alkil, hidroksihaloC1-6alkil, C1-6alkoksiC1-6alkil pri čemu svaki C1-6alkil može izborno biti supstituiran sa jednom ili dvije hidroksil grupe, -S(=O)2-C1-6alkil,-S(=O)2-haloC1-6alkil, -S(=O)2-NR14R15, C1-6alkil supstituiran sa -S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -S(=O)2-NR14R15, C1-6alkil supstituiran sa -NH-S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NH-S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -NH- S(=O)2-NR14R15, R13 ili C1-6alkil supstituiran sa R13; R6 predstavlja C3-8cikloalkil, C3-8cikloalkenil, fenil, 4-člani do 7-člani monociklični heterociklil koji sadrži barem jedan heteroatom izabran iz N, O ili S; navedeni C3-8cikloalkil, C3-8cikloalkenil, fenil, 4-člani do 7-člani monociklični heterociklil, izborno i svaki neovisno biva zamijenjen pomoću 1, 2, 3, 4 ili 5 substituenata, svaki supstituent se neovisno bira iz cijano, C1-6alkil, cijanoC1-6alkil, hidroksil, karboksil, hidroksiC1-6alkil, halogen, haloC1-6alkil, hidroksihaloC1-6alkil, C1-6alkoksi, C1-6alkoksiC1-6alkil, C1-6alkil-O-C(=O)-,-NR14R15, -C(=O)-NR14R15, C1-6alkil supstituiran sa-NR14R15, C1-6alkil supstituiran sa -C(=O)-NR14R15, -S(=O)2-C1-6alkil, -S(=O)2-haloC1-6alkil, -S(=O)2-NR14R15, C1-6alkil supstituiran sa -S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -S(=O)2-NR14R15, C1-6alkil supstituiran sa -NH-S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NH-S(=O)2-haloC1-6alkil ili C1-6alkil supstituiran sa -NH-S(=O)2-NR14R15; R7 i R8svaki neovisno predstavlja vodik, C1-6alkil, hidroksiC1-6alkil, haloC1-6alkil, hidroksihaloC1-6alkil ili C1-6alkoksiC1-6alkil; R9 predstavlja C3-8cikloalkil, C3-8cikloalkenil, fenil, naftil, ili 3-člani do 12-člani monociklični ili biciklični heterociklil koji sadrži barem jedan heteroatom izabran iz N, O ili S, navedeni C3-8cikloalkil, C3-8ciloalkenil, fenil, naftil, ili 3-člani do 12-člani monociklični ili biciklični heterociklil svaki izborno i svaki neovisno supstituiran sa 1, 2, 3, 4 ili 5 supstituenata, svaki supstituent se neovisno bira iz =O, C1-4alkil, hidroksil, karboksil, hidroksiC1-4alkil, cijano, cijanoC1-4alkil, C1-4alkil-O-C(=O)-, C1-4alkil supstituiran sa C1-4alkil-O-C(=O)-, C1-4alkil-C(=O)-, C1-4alkoksiC1-4alkil pri čemu svaki C1-4alkil može izborno biti supstituiran sa jednim ili dvije hidroksil grupe, halogen, haloC1-4alkil, hidroksihaloC1-4alkil, -NR14R15, -C(=O)-NR14R15, C1-4alkil supstituiran sa-NR14R15, C1-4alkil supstituiran sa -C(=O)-NR14R15, C1-4alkoksi, -S(=O)2-C1-4alkil, -S(=O)2-haloC1-4alkil, -S(=O)2-NR14R15, C1-4alkil supstituiran sa -S(=O)2-NR14R15, C1-4alkil supstituiran sa -NH-S(=O)2-C1-4alkil, C1-4alkil supstituiran sa -NH-S(=O)2-haloC1-4alkil, C1-4alkil supstituiran sa -NH-S(=O)2-NR14R15, R13, -C(=O)-R13, C1-4alkil supstituiran sa R13, fenil izborno supstituiran sa R16, fenilC1-6alkil pri čemu fenil je izborno supstituiran sa R16, 5-člani ili 6-člani aromatični monociklični heterociklil koji sadrži barem jedan heteroatom izabran iz N, O ili S pri čemu navedeni heterociklil izborno supstituiran sa R16;ili kada se dva supstituenta od R9 spoje na isti atom, oni mogu biti uzeti zajednoda formiraju4-člani do 7-člani zasićeni monociklični heterociklil koji sadrži barem jedan heteroatom izabran iz N, O ili S; R10 i R11 svaki neovisno predstavlja vodik, karboksil, C1-6alkil, cijanoC1-6alkil, C1-6alkil supstituiran sa -NR14R15, C1-6alkil supstituiran sa -C(=O)-NR14R15, haloC1-6alkil, hidroksiC1-6alkil, hidroksihaloC1-6alkil, C1-6alkoksi, C1-6alkoksiC1-6alkil pri čemu svaki C1-6alkil može biti izborno supstituiran sa jednom ili dvije hidroksil grupe, R6, C1-6alkil supstituiran sa R6, -C(=O)-R6, -C(=O)-C1-6alkil,-C(=O)-hidroksiC1-6alkil, -C(=O)-haloC1-6alkil,-C(=O)-hidroksihaloC1-6alkil, C1-6alkil supstituiran sa -Si(CH3)3, -S(=O)2-C1-6alkil, -S(=O)2-haloC1-6alkil,-S(=O)2-NR14R15, C1-6alkil supstituiran sa -S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -S(=O)2-NR14R15, C1-6alkil supstituiran sa -NH-S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NH-S(=O)2-haloC1-6alkil ili C1-6alkil supstituiran sa -NH-S(=O)2-NR14R15; R12 predstavlja vodik ili C1-4alkil izborno supstituiran sa C1-4alkoksi; R13 predstavlja C3-8cikloalkil ili zasićeni 4-člani do 6-člani monociklični heterociklil koji sadrži barem jedan heteroatom izabran iz N, O ili S, pri čemu je navedeni C3-3cikloalkil ili monociklični heterociklil izborno supstituiran sa 1, 2 ili 3 supstituenta svaki neovisno izabran iz halogena, hidroksil, C1-6alkil, -C(=O)-C1-6alkil, C1-6alkoksi, ili -NR14R15; R14 i R15 svaki neovisno predstavlja vodik, ili haloC1-4alkil, ili C1-4alkil izborno supstituiran supstituentom izabranim iz hidroksil, C1-4alkoksi, amino ili mono-ili di(C1-4alkil)amino; R16 predstavlja hidroksil, halogen, cijano, C1-4alkil, C1-4alkoksi, -NR14R15ili -C(=O)NR14R15; njegov N-oksid, njegovu farmaceutski prihvatljivu sol ili njegov solvat.
2. Uporaba prema patentnom zahtjevu 1 naznačena time što spoj formule (I) je spoj u kojem R1 predstavlja vodik, C1-6alkil, hidroksiC1-6alkil, haloC1-6alkil, C1-6alkoksiC1-6alkil pri čemu svaki C1-6alkil može izborno biti supstituiran sa jednom ili dvije hidroksil grupe, C1-6alkil supstituiran sa -NR4R5, C1-6alkil supstituiran sa -C(=O)-NR4R5, -S(=O)2-C1-6alkil, -S(=O)2-NR14R15, C1-6alkil supstituiran sa -S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NH-S(=O)2-C1-6alkil, R6, C1-6alkil supstituiran sa R6, C1-6alkil supstituiran sa - C(=O)-R6, hidroksiC1-6alkil supstituiran sa R6,ili sa C1-6alkil supstituiran sa -Si(CH3)3; pri čemu svaki R1aje vodik; pri čemu R10i R11svaki neovisno predstavlja vodik, C1-6alkil, cijanoC1-6alkil, C1-6alkil supstituiran sa -NR14R15, C1-6alkil supstituiran sa -C(=O)-NR14R15, halodC1-6alkil, hidroksiC1-6alkil, hidroksihaloC1-6alkil, C1-6alkoksi, C1-6alkoksiC1-6alkil pri čemu svaki C1-6alkil može biti izborno supstituiran sa jednom ili dvije hidroksil grupe, R6, C1-6alkil supstituiran sa R6, -C(=O)-R6, -C(=O)-C1-6alkil, -C(=O)-hidroksiC1-6alkil, -C(=O)-haloC1-6alkil,-C(=O)-hidroksihaloC1-6alkil, C1-6alkil supstituiran sa -Si(CH3)3, -S(=O)2-C1-6alkil, -S(=O)2-haloC1-6alkil, -S(=O)2-NR14R15, C1-6alkil supstituiran sa -S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -S(=O)2-haloC1-6alkil, C1-6alkil supstituiran sa -S(=O)2-NR14R15, C1-6alkil supstituiran sa -NH-S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NH-S(=O)2-haloC1-6alkil ili C1-6alkil supstituiran sa - NH- S(=O)2-NR14R15.
3. Uporaba prema patentnom zahtjevu 1, pri čemu spoj formule (I) je spoj u kojem je svako R1a vodik.
4. Uporaba prema bilo kojem od prethodnih patentnih zahtjeva pri čemu spoj formule (I) je spoj u kojem R1 predstavlja C1-6alkil.
5. Uporaba prema bilo kojem od prethodnih patentnih zahtjeva pri čemu spoj formule (I) je spoj u kojem R1 predstavlja CH3- ili CD3-.
6. Uporaba prema bilo kojem od prethodnih patentnih zahtjeva pri čemu spoj formule (I) je spoj u kojem se R2 neovisno bira iz halogena, cijano, C1-4alkil, C2-4alkenil, C1-4alkoksi, hidroksiC1-4alkil, hidroksiC1-4alkoksi, haloC1-4alkoksi, C1-4alkoksiC1-4alkil, R13, C1-4alkoksi supstituiran sa R13, -C(=O)-R13, C1-4alkil supstituiran sa NR7R8, C1-4alkoksi supstituiran sa NR7R8, -NR7R8 i -C(=O)-NR7R8.
7. Uporaba prema patentnom zahtjevu 6 pri čemu spoj formule (I) je spoj u kojem R2 predstavlja C1-4alkoksi.
8. Uporaba prema patentnom zahtjevu 6 ili patentnom zahtjevu 7 pri čemu spoj formule (I) je spoj u kojem R2 predstavlja CH3O- ili CD3O-.
9. Uporaba prema bilo kojem od prethodnih patentnih zahtjeva pri čemu spoj formule (I) je spoj u kojem R3 predstavlja C1-6alkil, hidroksiC1-6alkil, hidroksihaloC1-6alkil, haloC1-6alkil, C1-6alkil supstituiran sa -C(=O)-C1-6alkil, C1-6alkoksiC1-6alkil pri čemu svaki C1-6alkil može biti izborno supstituiran sa jednom ili dvije hidroksil grupe, C1-6alkil supstituiran sa R9, C1-6alkil supstituiran sa -NR10R11, C1-6alkil supstituiran sa hidroksil i -NR10R11, C1-6alkil supstituiran sa jednim ili dva halogena i -NR10R11, C1-6alki supstituiran sa -C(=O)-O-C1-6alkil, C1-6alkil supstituiran sa -O-C(=O)-NR10R11, C1-6alkil supstituiran sa karboksil, C1-6alkil supstituiran sa -NR12-S(=O)2-C1-6alkil, C1-6alkil supstituiran sa -NR12-S(=O)2-NR14R15, C1-6alkil supstituiran sa hidroksil i R9, -C1-6alkil-C(R12)=N-O-R12, C1-6alkil supstituiran sa -C(=O)-NR10R11, C1-6alkil supstituiran sa -C(=O)-R9, C2-6alkinil supstituiran sa R9, hidroksiC1-6alkoksi, C2-6alkenil, C2-6alkinil ili R13.
10. Uporaba prema patentnom zahtjevu 1 pri čemu spoj formule (I) je spoj u kojem R1 predstavlja C1-6alkil, svako R1a je vodik, n predstavlja cijeli broj jednak sa 2 i svako R2 predstavlja C1-4alkoksi, i R3 predstavlja C1-6alkil supstituiran sa -NR10R11.
11. Uporaba prema patentnom zahtjevu 10 pri čemu spoj formule (I) je spoj u kojem R10 predstavlja vodik ili C1-6alkil, i R11 predstavlja vodik, C1-6alkil, haloC1-6alkil, -C(=O)-C1-6alkil, -S(=O)2-C1-6alkil, -S(=O)2-NR14R15, hidroksiC1-6alkil, -C(=O)-hidroksihaloC1-6alkil, -C(=O)-R6, cijanoC1-6alkil, R6, C1-6alkil supstituiran sa R6, -C(=O)-haloC1-6alkil, ili C1-6alkil supstituiran sa -Si(CH3)3.
12. Uporaba prema patentnom zahtjevu 10 pri čemu spoj formule (I) je spoj u kojem R10 predstavlja vodik, -CH3,-CH2CH3 ili -CH(CH3)2 i R11 predstavlja vodik, -CH3, -CH2CH3 ili -CH(CH3)2,-CH2CF3, -CH2CHF2 ili -CH2CH2F, -C(=O)-CH3, -S(=O)2-CH3, -S(=O)2-CH2CH3,-S(=O)2-CH(CH3)2, -S(=O)2-N(CH3)2, -CH2CH2OH, -C(=O)-C(OH)(CH3)CF3, -C(=O)-ciklopropil, -CH2CH2CN, ciklopropan, ciklopentan, 2,2,6,6-tetrametil-piperidin,-CH2C3H5, -CH2-tetrahidrofuran, -C(=O)-(1-metil-piperidin-3-il), -C(=O)-CF3, -CH2Si(CH3)3, ili -CH2-C6H5.
13. Uporaba prema patentnom zahtjevu 10 pri čemu spoj formule (I) je spoj u kojem R1 predstavlja -CH3, svako R1a je vodik, n predstavlja cijeli broj jednak sa 2 i svako R2 predstavlja CH3O-, i R3predstavlja -CH2CH2NHCH(CH3)2.
14. Uporaba prema patentnom zahtjevu 10 pri čemu spoj formule (I) je spoj u kojem R1 predstavlja -CH3, svako R1a jevodik, n predstavlja cijeli broj jednak sa 2 i svako R2 predstavlja CH3O-, R3 predstavlja -CH2CH2-CH2-NHCH2CF3.
15. Uporaba prema patentnom zahtjevu 10 pri čemu spoj formule (I) je spoj u kome R1 predstavlja -CH3, svako R1a je vodik, n predstavlja cijeli broj jednak sa 2 i svako R2 predstavlja CH3O-, R3 predstavlja -CH2CH2NH2.
16. Uporaba prema patentnom zahtjevu 1 pri čemu spoj formule (I) je N-(3,5-dimetoksifenil)-N-[3-(1-metil-1H-pirazol-4- il)hinoksalin-6-il]-N’-(2,2,2-trifluoroetil)propan-1,3-diamin.
17. Uporaba prema patentnom zahtjevu 1 pri čemu spoj formule (I) je N-(3,5-dimetoksifenil)-N’-(1-metiletil)-N-[3-(1- metil-1H-pirazol-4-il)hinoksalin-6-il]etan-1,2-diamin.
18. Uporaba prema patentnom zahtjevu 1 pri čemu spoj formule (I) je N-(3,5-dimetoksifenil)-N-[3-(1-metil-1H-pirazol-4- il)hinoksalin-6-il]etan-1,2-diamin.
19. Uporaba prema bilo kojem od patentnih zahtjeva 1 do 18, pri čemu spoj formule (I) je spoj kao što je definirano u bilo kojem od patentnih zahtjeva 1 do 18 ili njegova farmaceutski prihvatljiva sol ili solvat.
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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8053440B2 (en) 2007-02-01 2011-11-08 Resverlogix Corporation Compounds for the prevention and treatment of cardiovascular diseases
NZ617779A (en) 2009-03-18 2015-08-28 Resverlogix Corp Novel anti-inflammatory agents
KR20180096823A (ko) 2009-04-22 2018-08-29 리스버로직스 코퍼레이션 신규한 소염제
GB201007286D0 (en) 2010-04-30 2010-06-16 Astex Therapeutics Ltd New compounds
GB201020179D0 (en) 2010-11-29 2011-01-12 Astex Therapeutics Ltd New compounds
US8754114B2 (en) 2010-12-22 2014-06-17 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
GB201118656D0 (en) 2011-10-28 2011-12-07 Astex Therapeutics Ltd New compounds
GB201118652D0 (en) 2011-10-28 2011-12-07 Astex Therapeutics Ltd New compounds
GB201118675D0 (en) 2011-10-28 2011-12-14 Astex Therapeutics Ltd New compounds
GB201118654D0 (en) 2011-10-28 2011-12-07 Astex Therapeutics Ltd New compounds
GB201209609D0 (en) * 2012-05-30 2012-07-11 Astex Therapeutics Ltd New compounds
GB201209613D0 (en) 2012-05-30 2012-07-11 Astex Therapeutics Ltd New compounds
EP3822273B1 (en) 2012-06-13 2024-04-10 Incyte Holdings Corporation Substituted tricyclic compounds as fgfr inhibitors
RS62233B1 (sr) 2012-07-11 2021-09-30 Blueprint Medicines Corp Inhibitori receptora fibroblast faktora rasta
WO2014026125A1 (en) 2012-08-10 2014-02-13 Incyte Corporation Pyrazine derivatives as fgfr inhibitors
MX338885B (es) * 2012-10-15 2016-05-04 Resverlogix Corp Compuestos utiles en la sintesis de compuestos de benzamida.
AU2013337277B2 (en) 2012-11-05 2018-03-08 Foundation Medicine, Inc. Novel NTRK1 fusion molecules and uses thereof
US9719970B2 (en) 2012-11-30 2017-08-01 Waters Technologies Corporation Methods and apparatus for the analysis of vitamin D metabolites
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
AR094812A1 (es) 2013-02-20 2015-08-26 Eisai R&D Man Co Ltd Derivado de piridina monocíclico como inhibidor del fgfr
TWI647220B (zh) 2013-03-15 2019-01-11 美商西建卡爾有限責任公司 雜芳基化合物及其用途
CN105307657B (zh) * 2013-03-15 2020-07-10 西建卡尔有限责任公司 杂芳基化合物和其用途
UA120248C2 (uk) 2013-03-15 2019-11-11 Селджен Кар Ллс Гетероарильні сполуки та їх застосування
SG10201708520YA (en) 2013-04-19 2017-12-28 Incyte Corp Bicyclic heterocycles as fgfr inhibitors
GB201307577D0 (en) * 2013-04-26 2013-06-12 Astex Therapeutics Ltd New compounds
CN104163794A (zh) * 2013-10-17 2014-11-26 中国药科大学 2-氨基芳环类血管内皮生长因子受体(vegfr)抑制剂及其制备方法和用途
CN110028491B (zh) 2013-10-25 2022-02-11 缆图药品公司 纤维母细胞生长因子受体抑制剂
WO2015108992A1 (en) 2014-01-15 2015-07-23 Blueprint Medicines Corporation Heterobicyclic compounds and their use as fgfr4 receptor inhibitors
HUE053653T2 (hu) 2014-03-26 2021-07-28 Astex Therapeutics Ltd FGFR inhibitor és IGF1R inhibitor kombinációi
JO3512B1 (ar) 2014-03-26 2020-07-05 Astex Therapeutics Ltd مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز
ES2856482T3 (es) 2014-03-26 2021-09-27 Astex Therapeutics Ltd Combinaciones de inhibidores de FGFR y cMet para el tratamiento del cáncer
CN105017227B (zh) * 2014-07-08 2018-03-09 四川百利药业有限责任公司 N‑(1h‑吡唑‑5‑基)喹唑啉‑4‑胺类化合物
KR102344105B1 (ko) 2014-08-18 2021-12-29 에자이 알앤드디 매니지먼트 가부시키가이샤 모노시클릭 피리딘 유도체의 염 및 이의 결정
US20160090633A1 (en) * 2014-09-26 2016-03-31 Janssen Pharmaceutica Nv Use of fgfr mutant gene panels in identifying cancer patients that will be responsive to treatment with an fgfr inhibitor
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
TWI695837B (zh) 2014-12-04 2020-06-11 比利時商健生藥品公司 作為激酶調節劑之***並嗒
JOP20200201A1 (ar) * 2015-02-10 2017-06-16 Astex Therapeutics Ltd تركيبات صيدلانية تشتمل على n-(3.5- ثنائي ميثوكسي فينيل)-n'-(1-ميثيل إيثيل)-n-[3-(ميثيل-1h-بيرازول-4-يل) كينوكسالين-6-يل]إيثان-1.2-ثنائي الأمين
WO2016134294A1 (en) 2015-02-20 2016-08-25 Incyte Corporation Bicyclic heterocycles as fgfr4 inhibitors
MA41551A (fr) 2015-02-20 2017-12-26 Incyte Corp Hétérocycles bicycliques utilisés en tant qu'inhibiteurs de fgfr4
MX2017010673A (es) 2015-02-20 2018-03-21 Incyte Corp Heterociclos biciclicos como inhibidores de receptores del factor de crecimiento fibroblastico (fgfr).
US10111885B2 (en) 2015-03-13 2018-10-30 Resverlogix Corp. Compositions and therapeutic methods for the treatment of complement-associated diseases
TWI703984B (zh) * 2015-04-03 2020-09-11 英商阿斯特克斯治療有限公司 用於癌症治療之fgfr/pd-1組合療法
US10478494B2 (en) * 2015-04-03 2019-11-19 Astex Therapeutics Ltd FGFR/PD-1 combination therapy for the treatment of cancer
HUE057090T2 (hu) * 2015-09-23 2022-04-28 Janssen Pharmaceutica Nv BI-heteroaril-szubsztituált 1,4-benzodiazepinek és alkalmazásuk rák kezelésében
US11155555B2 (en) * 2015-09-23 2021-10-26 Janssen Pharmaceutica Nv Compounds
CN105596330B (zh) * 2015-12-11 2018-10-16 深圳市坤健创新药物研究院 虚拟筛选化合物在制备激酶抑制剂中的应用和药物
CN107459519A (zh) 2016-06-06 2017-12-12 上海艾力斯医药科技有限公司 稠合嘧啶哌啶环衍生物及其制备方法和应用
WO2018049233A1 (en) 2016-09-08 2018-03-15 Nicolas Stransky Inhibitors of the fibroblast growth factor receptor in combination with cyclin-dependent kinase inhibitors
RU2019113764A (ru) * 2016-10-10 2020-11-13 Девелопмент Сентер Фор Байотекнолоджи Соединения хиноксалина в качестве ингибиторов рецепторной тирозинкиназы iii типа
AR111960A1 (es) 2017-05-26 2019-09-04 Incyte Corp Formas cristalinas de un inhibidor de fgfr y procesos para su preparación
JOP20190280A1 (ar) 2017-06-02 2019-12-02 Janssen Pharmaceutica Nv مثبطات fgfr2 لعلاج سرطان الأوعية الصفراوية
WO2019040109A1 (en) * 2017-08-21 2019-02-28 Celgene Corporation PROCESSES FOR THE PREPARATION OF (S) -TERT-BUTYL 4,5-DIAMINO-5-OXOPENTANOATE
US11661411B2 (en) 2017-12-01 2023-05-30 Board Of Regents Of The University Of Nebraska Quinoxaline compounds and uses thereof
MX2020008610A (es) 2018-03-28 2020-09-21 Eisai R&D Man Co Ltd Agente terapeutico para carcinoma hepatocelular.
WO2019209083A1 (ko) * 2018-04-26 2019-10-31 재단법인 의약바이오컨버젼스연구단 mTOR 저해제로서의 신규 화합물 및 이의 용도
CN112566912A (zh) 2018-05-04 2021-03-26 因赛特公司 Fgfr抑制剂的盐
CN112867716A (zh) 2018-05-04 2021-05-28 因赛特公司 Fgfr抑制剂的固体形式和其制备方法
AU2019342289A1 (en) 2018-09-21 2021-03-18 Janssen Pharmaceutica Nv Treatment of cholangiocarcinoma
EP3898615A1 (en) * 2018-12-19 2021-10-27 Array Biopharma, Inc. 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
KR20210145211A (ko) 2019-03-29 2021-12-01 얀센 파마슈티카 엔.브이. 요로상피세포암종의 치료를 위한 fgfr 티로신 키나제 저해제
CN113645975A (zh) 2019-03-29 2021-11-12 詹森药业有限公司 用于治疗尿路上皮癌的fgfr酪氨酸激酶抑制剂
WO2020208592A1 (en) * 2019-04-12 2020-10-15 Dr. Reddy’S Laboratories Limited Process for preparation of erdafitinib, its purification and amorphous solid dispersion
CN111909044A (zh) * 2019-05-09 2020-11-10 南京爱德程医药科技有限公司 2-(烷基氨基)乙基苯甲酸酯类化合物的合成方法
WO2021007269A1 (en) 2019-07-09 2021-01-14 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
TWI759829B (zh) * 2019-08-23 2022-04-01 財團法人生物技術開發中心 作為第iii型受體酪胺酸激酶抑制劑之雜環吡唑衍生物
US20220348662A1 (en) 2019-09-26 2022-11-03 Janssen Pharmaceutica Nv Use of fgfr inhibitors in fgfr-genetically altered cancers to enhance patient response to immune checkpoint inhibitors in sequential treatment settings
AU2020366006A1 (en) 2019-10-14 2022-04-21 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
US11566028B2 (en) 2019-10-16 2023-01-31 Incyte Corporation Bicyclic heterocycles as FGFR inhibitors
CN110790677B (zh) * 2019-11-05 2022-04-29 浙江工业大学 一种金刚烷甲酰胺类化合物及其制备方法和应用
EP4069696A1 (en) 2019-12-04 2022-10-12 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
KR20220131900A (ko) 2019-12-04 2022-09-29 인사이트 코포레이션 Fgfr 억제제의 유도체
CN113024517A (zh) * 2019-12-09 2021-06-25 武汉九州钰民医药科技有限公司 一种制备厄达替尼的方法
CN113024518A (zh) * 2019-12-09 2021-06-25 武汉九州钰民医药科技有限公司 一种厄达替尼的制备方法
CN114945367A (zh) * 2020-01-17 2022-08-26 贝达医药公司 作为fgfr激酶抑制剂的哒嗪和1,2,4-三嗪衍生物
TW202140012A (zh) 2020-02-12 2021-11-01 比利時商健生藥品公司 用於治療尿路上皮癌的ｆｇｆｒ酪胺酸激酶抑制劑和抗ｐｄ１藥劑
KR20220140781A (ko) 2020-02-12 2022-10-18 얀센 파마슈티카 엔.브이. 고위험 비근침윤성 방광암 치료를 위한 fgfr 티로신 키나제 억제제
WO2022040111A2 (en) 2020-08-17 2022-02-24 Teva Pharmaceuticals International Gmbh Solid state forms of erdafitinib salts and processes for preparation of erdafitinib
CN112920167B (zh) * 2020-08-19 2022-08-26 四川大学华西医院 靶向fgfr和hdac的双靶点抑制剂及其制备方法和应用、药物组合物及药剂
EP4210702A1 (en) 2020-09-14 2023-07-19 JANSSEN Pharmaceutica NV Fgfr inhibitor combination therapies
CA3217517A1 (en) 2021-05-19 2022-11-24 Christopher H. Moy Fgfr tyrosine kinase inhibitors for the treatment of advanced solid tumors
US11939331B2 (en) 2021-06-09 2024-03-26 Incyte Corporation Tricyclic heterocycles as FGFR inhibitors
CN117858872A (zh) 2021-06-22 2024-04-09 缆图药品公司 用于治疗癌症的杂环egfr抑制剂
TW202333720A (zh) 2021-10-12 2023-09-01 美商塔里斯生物醫學有限責任公司 用於膀胱內施用的厄達替尼調配物及系統
WO2023081923A1 (en) 2021-11-08 2023-05-11 Frequency Therapeutics, Inc. Platelet-derived growth factor receptor (pdgfr) alpha inhibitors and uses thereof
TW202400174A (zh) * 2022-02-18 2024-01-01 美商塔里斯生物醫學有限責任公司 用於膀胱內施用的Erdafitinib調配物及滲透系統
CN115108926B (zh) * 2022-04-02 2023-06-20 上海工程技术大学 一种用于制备厄达替尼的中间体化合物及制备方法

Family Cites Families (128)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2940972A (en) 1957-06-27 1960-06-14 Thomae Gmbh Dr K Tri-and tetra-substituted pteridine derivatives
US4666828A (en) 1984-08-15 1987-05-19 The General Hospital Corporation Test for Huntington's disease
US4683202A (en) 1985-03-28 1987-07-28 Cetus Corporation Process for amplifying nucleic acid sequences
US4801531A (en) 1985-04-17 1989-01-31 Biotechnology Research Partners, Ltd. Apo AI/CIII genomic polymorphisms predictive of atherosclerosis
US5272057A (en) 1988-10-14 1993-12-21 Georgetown University Method of detecting a predisposition to cancer by the use of restriction fragment length polymorphism of the gene for human poly (ADP-ribose) polymerase
US5192659A (en) 1989-08-25 1993-03-09 Genetype Ag Intron sequence analysis method for detection of adjacent and remote locus alleles as haplotypes
GB9125001D0 (en) 1991-11-25 1992-01-22 Ici Plc Heterocyclic compounds
AU6909194A (en) 1993-05-14 1994-12-12 Board Of Regents, The University Of Texas System Preparation of n-cyanodithioimino-carbonates and 3-mercapto-5-amino-1h-1,2,4-triazole
US5700823A (en) 1994-01-07 1997-12-23 Sugen, Inc. Treatment of platelet derived growth factor related disorders such as cancers
US6331555B1 (en) 1995-06-01 2001-12-18 University Of California Treatment of platelet derived growth factor related disorders such as cancers
CA2262403C (en) 1995-07-31 2011-09-20 Urocor, Inc. Biomarkers and targets for diagnosis, prognosis and management of prostate disease
US6218529B1 (en) 1995-07-31 2001-04-17 Urocor, Inc. Biomarkers and targets for diagnosis, prognosis and management of prostate, breast and bladder cancer
TW472045B (en) 1996-09-25 2002-01-11 Astra Ab Protein kinase C inhibitor compounds, method for their preparation, pharmaceutical composition thereof and intermediate used for their preparation
EP0991628B1 (en) 1997-05-28 2005-01-12 Aventis Pharmaceuticals Inc QUINOLINE AND QUINOXALINE COMPOUNDS WHICH INHIBIT PLATELET-DERIVED GROWTH FACTOR AND/OR P56lck TYROSINE KINASES
US6235740B1 (en) 1997-08-25 2001-05-22 Bristol-Myers Squibb Co. Imidazoquinoxaline protein tyrosine kinase inhibitors
UA71555C2 (en) 1997-10-06 2004-12-15 Zentaris Gmbh Methods for modulating function of serine/threonine protein kinases by 5-azaquinoline derivatives
WO2000042026A1 (en) 1999-01-15 2000-07-20 Novo Nordisk A/S Non-peptide glp-1 agonists
OA12010A (en) 1999-09-15 2006-04-19 Warner Lambert Co Pteridinones as kinase inhibitors.
DE10013318A1 (de) 2000-03-17 2001-09-20 Merck Patent Gmbh Formulierung enthaltend Chinoxalinderivate
WO2002076985A1 (en) 2001-03-23 2002-10-03 Smithkline Beecham Corporation Compounds useful as kinase inhibitors for the treatment of hyperproliferative diseases
EP1458383B1 (en) 2001-12-18 2007-11-21 Merck & Co., Inc. Heteroaryl substituted pyrazole modulators of metabotropic glutamate receptor-5
PT1463506E (pt) 2001-12-24 2009-12-10 Astrazeneca Ab Derivados de quinazolina substituídos como inibidores de aurora cinases
JP2003213463A (ja) 2002-01-17 2003-07-30 Sumitomo Chem Co Ltd 金属腐食防止剤および洗浄液
JP4394960B2 (ja) 2002-04-08 2010-01-06 メルク エンド カムパニー インコーポレーテッド Ａｋｔ活性阻害薬
US6962995B2 (en) 2002-07-10 2005-11-08 E. I. Du Pont De Nemours And Company Charge transport compositions and electronic devices made with such compositions
US7825132B2 (en) 2002-08-23 2010-11-02 Novartis Vaccines And Diagnostics, Inc. Inhibition of FGFR3 and treatment of multiple myeloma
KR20110050745A (ko) 2002-10-03 2011-05-16 탈자진 인코포레이티드 혈관항상성 유지제 및 그의 사용 방법
AR043059A1 (es) 2002-11-12 2005-07-13 Bayer Pharmaceuticals Corp Derivados de indolil pirazinona utiles para el tratamiento de trastornos hiper-proliferativos
US7098332B2 (en) 2002-12-20 2006-08-29 Hoffmann-La Roche Inc. 5,8-Dihydro-6H-pyrido[2,3-d]pyrimidin-7-ones
BRPI0406809A (pt) 2003-01-17 2005-12-27 Warner Lambert Co Heterociclos substituìdos de 2-aminopiridina como inibidores da proliferação celular
EP1620413A2 (en) 2003-04-30 2006-02-01 Cytokinetics, Inc. Compounds, compositions, and methods
JP4847868B2 (ja) 2003-05-14 2011-12-28 ニューロジェネティック ファーマシューティカルズ、 インコーポレイテッド 化合物、及び、アミロイドベータの調節におけるその使用
DE10323345A1 (de) 2003-05-23 2004-12-16 Zentaris Gmbh Neue Pyridopyrazine und deren Verwendung als Kinase-Inhibitoren
NZ544112A (en) 2003-05-23 2010-01-29 Zentaris Gmbh Novel pyridopyrazines and use thereof as kinase modulators
WO2005007099A2 (en) 2003-07-10 2005-01-27 Imclone Systems Incorporated Pkb inhibitors as anti-tumor agents
WO2005009437A1 (en) 2003-07-21 2005-02-03 Bethesda Pharmaceuticals, Inc. Design and synthesis of optimized ligands for ppar
JP2007501189A (ja) 2003-08-01 2007-01-25 ジェネラブス テクノロジーズ，インコーポレイテッド フラビウイルス科に対する二環式イミダゾール誘導体
DK1673092T3 (da) 2003-10-17 2007-12-17 4 Aza Ip Nv Heterocyklylsubstituerede pteridinderivater og anvendelsen deraf i terapi
JP4823914B2 (ja) 2003-11-07 2011-11-24 ノバルティス バクシンズ アンド ダイアグノスティックス，インコーポレーテッド Ｆｇｆｒ３の阻害および多発性骨髄腫の治療
EP1687277B1 (en) 2003-11-20 2018-04-04 Janssen Pharmaceutica NV 6-alkenyl and 6-phenylalkyl substituted 2-quinolinones and 2-quinoxalinones as poly(adp-ribose) polymerase inhibitors
JP2007512275A (ja) 2003-11-24 2007-05-17 エフ．ホフマン−ラ　ロシュ　アーゲー ピラゾリルおよびイミダゾリルピリミジン
EP1706385B1 (en) * 2003-12-23 2010-10-06 Astex Therapeutics Limited Pyrazole derivatives as protein kinase modulators
US7098222B2 (en) 2004-05-12 2006-08-29 Abbott Laboratories Bicyclic-substituted amines having cyclic-substituted monocyclic substituents
US7205316B2 (en) 2004-05-12 2007-04-17 Abbott Laboratories Tri- and bi-cyclic heteroaryl histamine-3 receptor ligands
NZ553087A (en) 2004-08-31 2010-12-24 Astrazeneca Ab Quinazolinone derivatives and their use as B-raf inhibitors
CN101039944B (zh) 2004-10-14 2010-05-05 霍夫曼-拉罗奇有限公司 具有cdk1抗增殖活性的1,5-二氮杂萘唑烷酮类
US20080207616A1 (en) 2004-10-15 2008-08-28 Astrazeneca Ab Quinoxalines as B Baf Inhhibitors
JP4966202B2 (ja) 2004-12-24 2012-07-04 スピニフェクス ファーマシューティカルズ ピーティーワイ リミテッド 治療または予防のための方法
NZ556686A (en) 2005-02-14 2010-01-29 Bionomics Ltd Novel tubulin polymerisation inhibitors
US9271963B2 (en) 2005-03-03 2016-03-01 Universitat Des Saarlandes Selective inhibitors of human corticosteroid synthases
EP1881986A2 (en) 2005-05-12 2008-01-30 Merck & Co., Inc. Tyrosine kinase inhibitors
AU2006247315A1 (en) 2005-05-18 2006-11-23 Wyeth 4, 6-diamino-[1,7] naphthyridine-3-carbonitrile inhibitors of Tpl2 kinase and methods of making and using the same
GB0513692D0 (en) 2005-07-04 2005-08-10 Karobio Ab Novel pharmaceutical compositions
WO2007023186A1 (en) 2005-08-26 2007-03-01 Laboratoires Serono S.A. Pyrazine derivatives and use as pi3k inhibitors
EP1957487A1 (de) 2005-11-11 2008-08-20 AEterna Zentaris GmbH Neue pyridopyrazine und deren verwendung als modulatoren von kinasen
EP1790342A1 (de) 2005-11-11 2007-05-30 Zentaris GmbH Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege
US8217042B2 (en) 2005-11-11 2012-07-10 Zentaris Gmbh Pyridopyrazines and their use as modulators of kinases
ME02736B (me) 2005-12-21 2017-10-20 Janssen Pharmaceutica Nv Triazolopiridazini kao modulatori tirozin kinaze
US7998978B2 (en) 2006-05-01 2011-08-16 Pfizer Inc. Substituted 2-amino-fused heterocyclic compounds
GB0609621D0 (en) 2006-05-16 2006-06-21 Astrazeneca Ab Novel co-crystal
JP2009537590A (ja) 2006-05-24 2009-10-29 ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング 四員複素環で置換された置換プテリジン
TWI398252B (zh) 2006-05-26 2013-06-11 Novartis Ag 吡咯并嘧啶化合物及其用途
AU2007271187A1 (en) 2006-07-03 2008-01-10 Vereniging Voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek En Patientenzorg Fused bicyclic compounds interacting with the histamine H4 receptor
EP2081928B1 (en) 2006-11-10 2014-02-26 Bristol-Myers Squibb Company Pyrrolo-pyridine kinase inhibitors
JP2008127446A (ja) 2006-11-20 2008-06-05 Canon Inc １，５−ナフチリジン化合物及び有機発光素子
CN102123712B (zh) 2006-12-13 2014-03-19 默沙东公司 使用igf1r抑制剂治疗癌症的方法
MX2009006688A (es) 2006-12-21 2009-06-30 Plexxikon Inc Compuestos y metodos para modulacion de cinasas, e indicaciones para ello.
JP2010514693A (ja) 2006-12-22 2010-05-06 ノバルティス アーゲー Ｐｄｋ１阻害のためのキナゾリン
MX2009006706A (es) * 2006-12-22 2009-07-02 Astex Therapeutics Ltd Compuestos heterociclicos biciclicos como inhibidores del receptor del factor de crecimiento de fibroblastos.
KR20080062876A (ko) 2006-12-29 2008-07-03 주식회사 대웅제약 신규한 항진균성 트리아졸 유도체
EP1990342A1 (en) 2007-05-10 2008-11-12 AEterna Zentaris GmbH Pyridopyrazine Derivatives, Process of Manufacturing and Uses thereof
US7592342B2 (en) * 2007-05-10 2009-09-22 Smithkline Beecham Corporation Quinoxaline derivatives as PI3 kinase inhibitors
JP2010529031A (ja) 2007-05-29 2010-08-26 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー Ｐｉ３キナーゼ阻害剤としてのナフチリジン誘導体
AR066879A1 (es) 2007-06-08 2009-09-16 Novartis Ag Derivados de quinoxalina como inhibidores de la actividad de cinasa de tirosina de las cinasas janus
PT2172450E (pt) 2007-06-20 2013-10-28 Mitsubishi Tanabe Pharma Corp Novo derivado sulfonamida de ácido malónico e sua utilização farmacêutica
JP5548123B2 (ja) 2007-06-21 2014-07-16 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ ６−｛ジフルオロ［６−（１−メチル−１Ｈ−ピラゾル−４−イル）［１，２，４］トリアゾロ［４，３−ｂ］ピリダジン−３−イル］メチル｝キノリンの多形および水和物の形態、塩、ならびに製造方法
WO2009009016A1 (en) 2007-07-06 2009-01-15 Osi Pharmaceuticals, Inc. Combination anti-cancer therapy
CN101827848B (zh) 2007-08-08 2012-11-07 葛兰素史密丝克莱恩有限责任公司 作为IGF-1R抑制剂用于治疗癌症的2-[(2-{苯基氨基}-1H-吡咯并[2,3-d]嘧啶-4-基)氨基]苯甲酰胺衍生物
WO2009019518A1 (en) 2007-08-09 2009-02-12 Astrazeneca Ab Pyrimidine compounds having a fgfr inhibitory effect
EP2173354A4 (en) * 2007-08-09 2011-10-05 Glaxosmithkline Llc CHINOXALIN DERIVATIVES AS PI3 KINASE INHIBITORS
US20090054304A1 (en) 2007-08-23 2009-02-26 Kalypsys, Inc. Heterocyclic modulators of tgr5 for treatment of disease
CA2704599C (en) 2007-11-16 2015-05-12 Incyte Corporation 4-pyrazolyl-n-arylpyrimidin-2-amines and 4-pyrazolyl-n-heteroarylpyrimidin-2-amines as janus kinase inhibitors
CA2722992A1 (en) 2008-05-05 2009-11-12 Schering Corporation Sequential administration of chemotherapeutic agents for treatment of cancer
CA2725185C (en) 2008-05-23 2016-10-25 Novartis Ag Derivatives of quinolines and quinoxalines as protein tyrosine kinase inhibitors
JP2012509342A (ja) 2008-11-20 2012-04-19 オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド 置換ピロロ［２，３−ｂ］−ピリジンおよび−ピラジン
EP2389376A1 (en) 2009-01-21 2011-11-30 Basilea Pharmaceutica AG Novel bicyclic antibiotics
AU2010208480A1 (en) 2009-02-02 2011-07-28 Msd K.K. Inhibitors of Akt activity
TW201041888A (en) 2009-05-06 2010-12-01 Plexxikon Inc Compounds and methods for kinase modulation, and indications therefor
CN104945379B (zh) 2009-06-12 2018-11-30 Abivax公司 用于治疗过早衰老和尤其是早衰的化合物
EA021275B9 (ru) 2009-09-03 2015-08-31 Байоэнердженикс Гетероциклические соединения, содержащая их фармацевтическая композиция и их применение для лечения pask-опосредованного заболевания
EP2473498A1 (en) 2009-09-04 2012-07-11 Bayer Pharma Aktiengesellschaft Substituted aminoquinoxalines as tyrosine threonine kinase inhibitors
US20110123545A1 (en) 2009-11-24 2011-05-26 Bristol-Myers Squibb Company Combination of vegfr2 and igf1r inhibitors for the treatment of proliferative diseases
EP2332939A1 (en) 2009-11-26 2011-06-15 Æterna Zentaris GmbH Novel Naphthyridine derivatives and the use thereof as kinase inhibitors
CN104940200B (zh) 2010-03-30 2019-06-28 维颂公司 多取代芳族化合物作为凝血酶的抑制剂
GB201007286D0 (en) 2010-04-30 2010-06-16 Astex Therapeutics Ltd New compounds
WO2011146591A1 (en) 2010-05-19 2011-11-24 Millennium Pharmaceuticals, Inc. Substituted hydroxamic acids and uses thereof
CA2804304C (en) 2010-05-24 2020-02-25 Intellikine, Llc Heterocyclic compounds and uses thereof
GB201020179D0 (en) 2010-11-29 2011-01-12 Astex Therapeutics Ltd New compounds
CN102532141A (zh) 2010-12-08 2012-07-04 中国科学院上海药物研究所 [1，2，4]***并[4，3-b][1，2，4]三嗪类化合物、其制备方法和用途
CA2825605C (en) 2011-01-31 2019-05-07 Novartis Ag Heterocyclic derivatives
AU2012212075A1 (en) 2011-02-02 2013-07-18 Amgen Inc. Methods and compositons relating to inhibition of IGF-1R
AR085397A1 (es) 2011-02-23 2013-09-25 Intellikine Inc Combinacion de inhibidores de quinasa y sus usos
WO2012118492A1 (en) 2011-03-01 2012-09-07 Array Biopharma Inc. Heterocyclic sulfonamides as raf inhibitors
US9896730B2 (en) 2011-04-25 2018-02-20 OSI Pharmaceuticals, LLC Use of EMT gene signatures in cancer drug discovery, diagnostics, and treatment
CN107245056A (zh) 2011-08-26 2017-10-13 润新生物公司 化学实体、组合物及方法
WO2013040515A1 (en) 2011-09-14 2013-03-21 Neupharma, Inc. Certain chemical entities, compositions, and methods
WO2013043935A1 (en) 2011-09-21 2013-03-28 Neupharma, Inc. Certain chemical entites, compositions, and methods
WO2013052699A2 (en) 2011-10-04 2013-04-11 Gilead Calistoga Llc Novel quinoxaline inhibitors of pi3k
PL2771342T3 (pl) 2011-10-28 2016-11-30 Nowe pochodne puryny i ich zastosowanie w leczeniu chorób
GB201118654D0 (en) 2011-10-28 2011-12-07 Astex Therapeutics Ltd New compounds
JO3210B1 (ar) 2011-10-28 2018-03-08 Merck Sharp & Dohme مثبط منصهر لبروتين نقل الكوليسترليستير اوكسازوليدينون ثمائي الحلقة
GB201118652D0 (en) 2011-10-28 2011-12-07 Astex Therapeutics Ltd New compounds
GB201118675D0 (en) 2011-10-28 2011-12-14 Astex Therapeutics Ltd New compounds
GB201118656D0 (en) 2011-10-28 2011-12-07 Astex Therapeutics Ltd New compounds
US9481911B2 (en) 2012-03-08 2016-11-01 Astellas Pharma Inc. Methods for detecting FGFR3/TACC3 fusion genes
GB201209613D0 (en) 2012-05-30 2012-07-11 Astex Therapeutics Ltd New compounds
GB201209609D0 (en) * 2012-05-30 2012-07-11 Astex Therapeutics Ltd New compounds
US20150203589A1 (en) 2012-07-24 2015-07-23 The Trustees Of Columbia University In The City Of New York Fusion proteins and methods thereof
WO2014113729A2 (en) 2013-01-18 2014-07-24 Foundation Mecicine, Inc. Methods of treating cholangiocarcinoma
GB201307577D0 (en) 2013-04-26 2013-06-12 Astex Therapeutics Ltd New compounds
JP2016527274A (ja) 2013-08-02 2016-09-08 イグナイタ インコーポレイテッド ＡＸＬ／ｃＭＥＴ阻害剤を単独または他の薬剤と組み合わせて用いて各種がんを治療する方法
US9221804B2 (en) 2013-10-15 2015-12-29 Janssen Pharmaceutica Nv Secondary alcohol quinolinyl modulators of RORγt
JO3512B1 (ar) 2014-03-26 2020-07-05 Astex Therapeutics Ltd مشتقات كينوكسالين مفيدة كمعدلات لإنزيم fgfr كيناز
ES2856482T3 (es) 2014-03-26 2021-09-27 Astex Therapeutics Ltd Combinaciones de inhibidores de FGFR y cMet para el tratamiento del cáncer
HUE053653T2 (hu) 2014-03-26 2021-07-28 Astex Therapeutics Ltd FGFR inhibitor és IGF1R inhibitor kombinációi
JOP20200201A1 (ar) 2015-02-10 2017-06-16 Astex Therapeutics Ltd تركيبات صيدلانية تشتمل على n-(3.5- ثنائي ميثوكسي فينيل)-n'-(1-ميثيل إيثيل)-n-[3-(ميثيل-1h-بيرازول-4-يل) كينوكسالين-6-يل]إيثان-1.2-ثنائي الأمين
MX2017010595A (es) 2015-02-19 2018-11-12 Bioclin Therapeutics Inc Métodos, composiciones, y equipos para tratamiento de cáncer.
US10478494B2 (en) 2015-04-03 2019-11-19 Astex Therapeutics Ltd FGFR/PD-1 combination therapy for the treatment of cancer

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