ME02210B - Derivati pirolotriazinona kao pi3k inhibitori - Google Patents

Derivati pirolotriazinona kao pi3k inhibitori

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ME02210B
ME02210B MEP-2015-170A MEP2015170A ME02210B ME 02210 B ME02210 B ME 02210B ME P2015170 A MEP2015170 A ME P2015170A ME 02210 B ME02210 B ME 02210B
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group
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nitrogen atom
formula
atom
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Anchuela Francisco Javier Bernal
Riera Marta Carrascal
Javaloyes Juan Francisco Caturla
Ferrer Jordi Gracia
Victor Giulio Matassa
Belart Emma Terricabras
Moll Joan Taltavull
Sola Montserrat Erra
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Almirall Sa
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Claims (1)

1. Jedinjenje formule (I), ili njegova farmaceutski prihvatljiva so, ili solvat, ili N-oksid, ili stereoizomer ili deuterizovani derivat: Formula (I) pri čemu X predstavlja atom azota ili –CR6 grupu; n predstavlja 0, 1, 2 ili 3; Ra i Rb svaki nezavisno predstavlja atom vodonika, C1-C4 haloalkil grupu, C1-C4 hidroksialkil grupu ili linearnu ili razgranatu C1-C4 alkil grupu; R1 predstavlja atom vodonika, linearnu ili razgranatu C1-C4 alkil grupu, C1-C4 haloalkil grupu, C3-C10 cikloalkil grupu, C3-C10 cikloalkenil grupu, monocikličnu ili bicikličnu C6-C14arilgrupu, 5- do 14- monocikličnu ili bicikličnu heteroaril grupu koja sadrži bar jedan heteroatom izabran izmedu O, S i N, ili 5-do 14- članu monocikličnu ili bicikličnu heterociklil grupu koja sadrži bar jedan heteroatom izabran izmedu O, S i N, pri čemu su cikloalkil, cikloalkenil, aril, heteroaril, i heterociklil grupe nesupstituisane ili su supstituisane sa jednim ili više supstituenata izabranih između atoma halogena, hidroksil grupe, cijano grupe, linearne ili razgranate C1-C4 alkil grupe, C1-C4 haloalkil grupe, C1-C4 hidroksialkil grupe, C3-C4 cikloalkil grupe, -(CH2)1-3CN grupe, -(CH2)0-3OR8 grupe, (CH2)0-3NR7R8 grupe, -C(O)-(CH2)1-3-CN grupe, -C(O)-(CH2)0-3-R8 grupe, -C(O)-(CH2)0-3-NR7R8 grupe, - S(O)2(CH2)0-3-R8 grupe, -S(O)2(CH2)0-3-NR7R8 grupe ili -(CH2)0-3-( fenil)-OR8 grupe; R2 i R3 svaki nezavisno predstavlja atom vodonika, atom halogena, hidroksil grupu, cijano grupu, C1-C4 alkoksi grupu, C1-C4 haloalkil grupu, C1-C4 hidroksialkil grupu, C3-C7 cikloalkil grupu, -NR 'R" grupu, ili linearnu ili razgranatu C1-C6 alkil grupu, pri čemu je alkil grupa nesupstituisana ili je supstituisana sa jednim ili više supstituenata izabranih izmedu C1-C4 alkoksi grupe, cijano grupe ili C3-C7 cikloalkil grupe; R4 predstavlja atom vodonika, C1-C4 alkoksi grupu, C1-C4 haloalkil grupu, C1-C4hidroksiaikii grupu, C3-C7 cikioalkil grupu, -(CH2)1-4NR 'R" grupu, ili linearnu ili razgranatu C1-C4 aikil grupu, pri čemu je alkil grupa nesupstituisana ili je supstituisana sa jednim ili više supstituenata izabranih izmedu C1-C4 alkoksi grupe, cijano grupe, C3-C4cikloalkil grupe, -C(O)-(CH2)0-3R grupe ili -C(O)-(CH2)0-3-NR'R" grupe; R6 predstavlja atom vodonika; atom halogena; hidroksil grupu; cijano grupu; C1-C4 alkoksi grupu; C1-C4 haloalkil grupu; linearnu ili razgranatu C1-C4hidroksialkil grupu; C3-C7 cikloalkil grupu; -(CH2)0-3-NR'R" grupu; -(CH2)1-3-O(C1-C4 alkil grupu); -(CH2)0-3OC(O)-( C1-C4 alkil grupu); -(CH2)0-3C(O)O-(C1-C4 alkil grupu); -C(O)-(CH2)0-3-NR'R" grupu; -(CH2)0-3-C(O)OH grupu; -(CH2)0-3 -(5- do 14- članu monocikličnu ili bicikličnu heteroaril grupu koja sadrži bar jedan heteroatom izabran između O, S i N); -(CH2)0-3-(5- do 14- članu monocikličnu ili bicikličnu heterociklil grupu koja sadrži bar jedan heteroatom izabran izmedu O, S i N); ili linearnu ili razgranatu C1-C4 alkil grupu, pri čemu je alkil grupa nesupstituisana ili je supstituisana sa jednim ili više supstituenata izabranih izmedu C1-C4 alkoksi grupe, cijano grupe ili C3-C4 cikloalkil grupe; pri čemu su heteroaril i heterociklil grupe nesupstituisane ili su supstituisane sa jednim ili više supstituenata izabranih izmedu atoma halogena, hidroksil grupe, cijano grupe, linearne ili razgranate C1-C4 alkil grupe ili C1-C4 haloalkil grupe, R7 i Rb svaki nezavisno predstavlja atom vodonika, C1-C4 haloalkil grupu, C1-C4 hidroksialkil grupu ili linearnu ili razgranatu C1-C4 alkil grupu, pri čemu je alkil grupa nesupstituisana ili je supstituisana sa jednim ili više supstituenata izabranih izmedu C1-C4 alkoksi grupe, cijano grupe ili C3-C4 cikloalkil grupe; R' i R" svaki nezavisno predstavlja atom vodonika, hidroksil grupu, C1-C4alkoksi grupu ili linearnu ili razgranatu C1-C4 alkil grupu. R5 predstavlja grupu izabranu izmedu: i. grupe formule (lla) * I formula ( lla ) ii) grupe formule (llb) formula (llb) iii) grupe formule (llc) *IR17 Formula (llc) pri čemu Y predstavlja linker izabran izmedu -NR'- grupe, -O- ili -S-; pri cemu je R ' onakav kao što je gore definisano;(*) predstavlja gde je R5 vezan za atom ugljenika povezan sa R4 i pirolotriazinon grupom; W1 predstavlja -CR11 grupu i W2 predstavlja atom azota, ili W1 predstavlja atom azota i W2 predstavlja -CR12 grupu; G1 predstavlja -CR14 grupu i G2 predstavlja atom azota, ili G1 predstavlja atom azota i G2 predstavlja -CR15 grupu, ili G1 predstavlja -CR14 grupu i -CR14 predstavlja -CR15 grupu; G3 predstavlja atom azota, ili -CR15 grupu;R9, R10 i R12, R13, R14 i R16 svaki nezavisno predstavlja atom vodonika; atom halogena; C1-C4alkoksi; C1-C4 haloalkil grupu; C1-C4 hidroksialkil grupu; C3-C4 cikloalkil grupu; -(CH2)0-3CN grupu; -C(O)-( CH2)1-3-CNgrupu; -C(O)-(CH2)0-3-R' grupu; -C(O)-(CH2)0-3-NR'R"; (CH2)0-3NR'R" grupu; linearnu ili razgranatu C1-C4 alkil grupu, pri čemu je alkil grupa nesupstituisana ili je supstituisana sa jednim ili više supstituenata izabranih iz C1-C4 alkoksi grupe;pri čemu su R' i R" onakvi kao sto je gore definisano; R17 predstavlja grupu izabranu između a) grupe formule (llla), b) grupe formule (lllb), formula (llla) formula (lllb) c) grupe formule (lllc), i d) grupe formule (llld), pri čemu G4 predstavija atom azota ili –CR22 grupu; G5 i G6 svaki nezavisno predstavija atom azota ili atom ugijenika, pri čemu kada jedan od G5 i G6 predstavija atom azota, onda preostali predstavija atom ugijenika; G7 predstavija -NH grupu ili -CH grupu; G8 predstavlja atom azota ili –CR23 grupu; G9 predstavlja atom azota ili -CR24 grupu; G10 predstavlja atom azota ili -CR25 grupu; G11 predstavlja atom azota ili -CR26 grupu; G12 predstavlja atom azota ili -CR 27 grupu; G13 predstavija atom azota iii -CR28 grupu; G14 i G15 svaki nezavisno predstavlja atom azota ili -atom ugljenika, pri čemu kada jedan od G14i G15 predstavija atom azota, onda preostali predstavlja atom ugljenika; G16 predstavlja -NH grupu ili -CH grupu; G17 predstavlja atom azota ili -CR29grupu; G18 predstavlja atom azota ili -CR30 grupu; R18, R19, R20, R21, R22, R23, R24, R25, R26, R27, R28, R29 i R30 svaki nezavisno predstavlja atom vodonika, atom halogena, C1-C4 alkoksi grupu, C1-C4 haloaikil grupu, C1-C4 hidroksiaikil grupu, C3-C4 cikloalkil grupu, -(CH2)0-3CN grupu, -C(O)-(CH2)1-3-CN grupu, -C(O)-(CH2)0-3-R' grupu, - C(O)-(CH2)0-3-NR 'R", -(CH2)0-3NR'R" grupu, ili linearnu ili razgranatu C1-C4 alkil grupu, pri čemu je alkil grupa nesupstituisana ili je supstituisana sa jednim ili više supstituenata izabranih izmedu C1-C4 aikoksi grupe, cijano grupe ili C3-C4 cikloalkil grupe; pri čemu su R ' i R" onakvi kao sto je gore definisano; i pri cemu je Y onakav kao sto je gore definisano; ili u slucaju daY predstavlja -NR '- grupu, onda R4 zajedno sa -NR'- grupom i atomom ugljenika za koji su oba, i R4 i -NR'- grupa vezani obrazuje 4- do 7-članu, zasićenu heterociklil grupu koja sadrzi N, pri čemu je heterociklil grupa nesupstituisana ili je supstituisana sa jednim ili više supstituenata izabranih izmedu atoma halogena, hidroksil grupe, cijano grupe, -CHF2 grupe ili -CF3 grupe _
MEP-2015-170A 2011-04-29 2012-04-26 Derivati pirolotriazinona kao pi3k inhibitori ME02210B (me)

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EP11382124A EP2518070A1 (en) 2011-04-29 2011-04-29 Pyrrolotriazinone derivatives as PI3K inhibitors
US201161502550P 2011-06-29 2011-06-29
PCT/EP2012/057671 WO2012146666A1 (en) 2011-04-29 2012-04-26 Pyrrolotriazinone derivatives as pi3k inhibitors
EP12717685.7A EP2702061B9 (en) 2011-04-29 2012-04-26 Pyrrolotriazinone derivatives as pi3k inhibitors

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EP2518070A1 (en) 2011-04-29 2012-10-31 Almirall, S.A. Pyrrolotriazinone derivatives as PI3K inhibitors
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