HRP20160655T1 - Supstituirani spojevi purina i 7-deazapurina kao modulatori epigenetskih enzima - Google Patents

Supstituirani spojevi purina i 7-deazapurina kao modulatori epigenetskih enzima Download PDF

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HRP20160655T1
HRP20160655T1 HRP20160655TT HRP20160655T HRP20160655T1 HR P20160655 T1 HRP20160655 T1 HR P20160655T1 HR P20160655T T HRP20160655T T HR P20160655TT HR P20160655 T HRP20160655 T HR P20160655T HR P20160655 T1 HRP20160655 T1 HR P20160655T1
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Edward James Olhava
Richard Chesworth
Kevin Wayne Kuntz
Victoria Marie Richon
Roy Macfarlane Pollock
Scott Richard Daigle
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Epizyme, Inc.
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Claims (17)

1. Spoj s Formulom (IV) ili njegov N-oksid ili njegova farmaceutski prihvatljiva sol: [image] naznačen time da A je O ili CH2; Q je H, NH2, NHRb, NRbRc, OH, Rb, ili ORb, gdje svaki od Rb i Rc neovisno je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 7-člani heterocikloalkil, 5 do 10-člani heteroaril, ili -M1-T1 gdje M1 je veza ili C1-C6 alkil poveznica proizvoljno supstituirana s halo, cijano, hidroksil ili C1-C6 alkoksil i T1 je C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, ili 5 do 10-člani heteroaril, ili Rb i Rc, zajedno sa N atomom na koji su oni vezani, tvore 4 do 7-člani heterocikloalkil koji ima 0 ili 1 dodatnih heteroatoma na N atomu proizvoljno supstituiran s C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, halo, hidroksil, karboksil, C(O)OH, C(O)O-C1-C6 alkil, OC(O)-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, ili 5 do 6-člani heteroaril, i svaki od Rb, Rc, i T1 je proizvoljno supstituiran s jednim ili više supstituenata odabranih iz skupine koja sadrži C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, halo, hidroksil, karboksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, i 5 do 6-člani heteroaril; X je N ili CRx, gdje Rx je H, halo, hidroksil, karboksil, cijano, ili RS1, RS1 je amino, C1-C6 alkoksil, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, ili 5 do 6-člani heteroaril, i RS1 je proizvoljno supstituiran s jednim ili više supstituenata odabranih iz skupine koja sadrži halo, hidroksil, karboksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, i 5 do 6-člani heteroaril; Y je H, Rd, SO2Rd, ili CORd, Rd je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, ili 5 do 6-člani heteroaril, te Rd je proizvoljno supstituiran s jednim ili više supstituenata odabranih iz skupine koja sadrži C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, halo, hidroksil, karboksil, cijano, C1-C6 alkoksil, C1-C6 alkilsulfonil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, i 5 do 6-člani heteroaril i svaki od which C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, i 5 do 6-člani heteroaril supstituenti na Rd je dodatno proizvoljno supstituiran s C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, halo, hidroksil, karboksil, C(O)OH, C(O)O-C1-C6 alkil, OC(O)-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, ili 5 do 6-člani heteroaril; svaki od R1 i R2 neovisno, je H, halo, hidroksil, karboksil, cijano, RS2, RS2 je amino, C1-C6 alkoksil, C1-C6 alkil, C2-C6 alkenil, ili C2-C6 alkinil, i svaki RS2 je proizvoljno supstituiran s jednim ili više supstituenata odabranih iz skupine koja sadrži halo, hidroksil, karboksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, i 5 do 6-člani heteroaril; svaki od Re, Rf, Rg, i Rh, neovisno je -M2-T2, u kojem M2 je veza, SO2, SO, S, CO, CO2, O, O-C1-C4 alkil poveznica, C1-C4 alkil poveznica, NH, ili N(Rt), Rt je C1-C6 alkil, i T2 je H, halo, ili RS4, RS4 je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 8-člani heterocikloalkil, ili 5 do 10-člani heteroaril, i svaki od O-C1-C4 alkil poveznice, C1-C4 alkil poveznice, Rt, i RS4 je proizvoljno supstituiran s jednim ili više supstituenata odabranih iz skupine koja sadrži halo, hidroksil, karboksil, cijano, C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 6-člani heterocikloalkil, i 5 do 6-člani heteroaril, i m je 0, 1, ili 2.
2. Spoj prema zahtjevu 1, naznačen time da A je O.
3. Spoj prema zahtjevu 1, naznačen time da A je O i m je 2.
4. Spoj prema zahtjevu 1, naznačen time da X je N.
5. Spoj prema zahtjevu 1, naznačen time da Q je NH2 ili NHRb, gdje Rb je -M1-T1, M1 je veza ili C1-C6 alkil poveznica i T1 je C3-C8 cikloalkil.
6. Spoj prema zahtjevu 1, naznačen time da R1 i R2, su svaki H.
7. Spoj prema zahtjevu 1, naznačen time da Y je Rd.
8. Spoj prema zahtjevu 7, naznačen time da Rd je C1-C6 alkil proizvoljno supstituiran s C3-C8 cikloalkil ili halo, ili Rd je C3-C8 cikloalkil proizvoljno supstituiran s C1-C6 alkil ili halo.
9. Spoj prema zahtjevu 1, naznačen time da barem jedan od Re, Rf, Rg, i Rh je halo, C1-C6 alkoksil proizvoljno supstituiran s jednim ili više halo, C1-C6 alkilsulfonil proizvoljno supstituiran s jednim ili više halo, C1-C6 alkil proizvoljno supstituiran s jednim ili više supstituenata odabranih od halo, hidroksi, i C1-C6 alkoksil, C3-C8 cikloalkil proizvoljno supstituiran s jednim ili više C1-C6 alkil, ili 4 do 8-člani heterocikloalkil proizvoljno supstituiran s jednim ili više C1-C6 alkil.
10. Spoj prema zahtjevu 9, naznačen time da je barem jedan od Re, Rf, Rg, i Rh izabran iz skupine koju čine F, Cl, Br, CF3, OCF3, SO2CF3, oksetanil, C1-C4 alkoksil, C3-C8 cikloalkil proizvoljno supstituiran s jednim ili više supstituenata odabranih od C1-C4 alkil i CN, i C1-C4 alkil proizvoljno supstituiran s jednim ili više supstituenata odabranih od CN, halo, C3-C8 cikloalkil, hidroksi i C1-C6 alkoksil.
11. Spoj prema zahtjevu 1, naznačen time da je odabran iz skupa koji čine [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] [image] i N-oksidi i njihove farmaceutski prihvatljive soli.
12. Spoj prema zahtjevu 1, naznačen time da je spoj odabran od [image] i njegovih farmaceutski prihvatljivih soli. Farmaceutski pripravak naznačen time da sadrži terapijski učinkovitu količinu spoja prema bilo kojem od zahtjeva 1 do 12 i farmaceutski prihvatljiv nosač.
13. Spoj prema bilo kojem od patentnih zahtjeva 1 do 12 ili farmaceutski pripravak prema zahtjevu 13, naznačen time da je za upotrebu za terapiju.
14. Farmaceutski pripravak prema zahtjevu 13 naznačen time da je za upotrebu za liječenje raka.
15. Farmaceutski pripravak prema zahtjevu 13 naznačen time da je za upotrebu za liječenje hematološkog raka ili leukemije.
16. Farmaceutski pripravak za upotrebu prema zahtjevu 16, naznačen time da leukemija je akutna mijeloična leukemija, akutna limfocitna leukemija ili mješovita leukemija.
17. Farmaceutski pripravak za upotrebu prema zahtjevu 16, pri čemu leukemija je MLL-presložena leukemija ili leukemija naznačena time da ima parcijalnu tandem duplikaciju MLL gena (MLL-PTD).
HRP20160655TT 2010-12-03 2016-06-10 Supstituirani spojevi purina i 7-deazapurina kao modulatori epigenetskih enzima HRP20160655T1 (hr)

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PCT/US2011/063044 WO2012075381A1 (en) 2010-12-03 2011-12-02 Substituted purine and 7 - deazapurine compounds as modulators of epigenetic enzymes

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CN103391939B (zh) * 2010-12-03 2016-03-09 Epizyme股份有限公司 作为表观遗传酶调节剂的经取代的嘌呤和7-氮杂嘌呤化合物
AU2011336272A1 (en) 2010-12-03 2013-06-20 Epizyme, Inc. 7-deazapurine modulators of histone methyltransferase, and methods of use thereof
US9029343B2 (en) 2010-12-03 2015-05-12 Epizyme, Inc. Modulators of histone methyltransferase, and methods of use thereof
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