HRP20160266T1 - 5-supstituirani derivati kinazolinona kao sredstva protiv raka - Google Patents

5-supstituirani derivati kinazolinona kao sredstva protiv raka Download PDF

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Publication number
HRP20160266T1
HRP20160266T1 HRP20160266TT HRP20160266T HRP20160266T1 HR P20160266 T1 HRP20160266 T1 HR P20160266T1 HR P20160266T T HRP20160266T T HR P20160266TT HR P20160266 T HRP20160266 T HR P20160266T HR P20160266 T1 HRP20160266 T1 HR P20160266T1
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HR
Croatia
Prior art keywords
optionally substituted
alkyl
halogens
hydrogen
compound
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HRP20160266TT
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English (en)
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George W. Muller
Hon-Wah Man
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Celgene Corporation
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Publication of HRP20160266T1 publication Critical patent/HRP20160266T1/hr

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Claims (17)

1. Spoj formule (I): [image] , ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer, naznačen time što je namijenjen upotrebi u postupku liječenja, tretmana ili sprječavanja raka krvi ili koštane srž, gdje je: R1: vodik; halogen; -(CH2)nOH; (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; (C1-C6)alkoksi, izborno supstituiran s jednim ili više halogena; ili -(CH2)nNHRa, gdje je Ra: vodik; (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; -(CH2)n-(6 do 10-eročlani aril); -C(O)-(CH2)n-(6 do 10-eročlani aril) ili -C(O)-(CH2)n-(6 do 10-eročlani heteroaril), gdje su aril ili heteroaril izborno supstituirani jednim ili više od: halogena; -SCF3; (C1-C6)alkila, koji je i sam izborno supstituiran s jednim ili više halogena; ili (C1-C6)alkoksi, koji je i sam izborno supstituiran s jednim ili više halogena; -C(O)-(C1-C8)alkil, gdje je alkil izborno supstituiran s jednim ili više halogena; -C(O)-(CH2)n-(C3-C10-cikloalkil); -C(O)-(CH2)n-NRbRc, gdje je svaki od Rb i Rc neovisno: vodik; (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; (C1-C6)alkoksi, izborno supstituiran s jednim ili više halogena; ili 6 do 10-eročlani aril, izborno supstituiran s jednim ili više od: halogena; (C1-C6)alkil, koji je i sam izborno supstituiran s jednim ili više halogena; ili (C1-C6)alkoksi, koji je i sam izborno supstituiran s jednim ili više halogena; -C(O)-(CH2)n-O-(C1-C6)alkil; ili -C(O)-(CH2)n-O-(CH2)n-(6 do 10-eročlani aril); R2: vodik; -(CH2)nOH; fenil; -O-(C1-C6)alkil; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; R3: vodik; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; i n 0, 1 ili 2.
2. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 1, naznačen time što ima strukturu formule (II): [image] , ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer, gdje je: R4: vodik; halogen; -(CH2)nOH; (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; ili (C1-C6)alkoksi, izborno supstituiran s jednim ili više halogena; R5: vodik; -(CH2)nOH; fenil; -O-(C1-C6)alkil; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; R6: vodik; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; i n 0, 1 ili 2.
3. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 2, ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer, naznačen time što R4 je metil ili metoksi; ili R4 je F ili Cl; ili R4 je -CF3.
4. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 2, naznačen time što je: [image] [image] ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer.
5. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 1, naznačen time što ima strukturu formule (III): [image] , ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer, gdje je: Rd: vodik; (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; -C(O)-(C1-C8)alkil, gdje je alkil izborno supstituiran s jednim ili više halogena; -C(O)-(CH2)n-(C3-C10-cikloalkil); -C(O)-(CH2)n-NReRf, gdje je svaki od Re i Rf neovisno: vodik; (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; ili (C1-C6)alkoksi, izborno supstituiran s jednim ili više halogena; ili -C(O)-(CH2)n-O-(C1-C6)alkil; R7: vodik; -(CH2)nOH; fenil; -O-(C1-C6)alkil; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; R8: vodik; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; i n 0, 1 ili 2.
6. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 5, ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer, naznačen time što R7 je metil; ili Rd je -C(O)-(C1-C6)alkil; ili Rd je -C(O)-CH2-O-(C1-C6)alkil.
7. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 5, naznačen time što je: [image] [image] ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer.
8. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 1, naznačen time što ima strukturu formule (IV): [image] , ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer, gdje je: Rg: -(CH2)n-(6 do 10-eročlani aril); -C(O)-(CH2)n-(6 do 10-eročlani aril) ili -C(O)-(CH2)n-(6 do 10-eročlani heteroaril), gdje su aril ili heteroaril izborno supstituirani jednim ili više od: halogena; -SCF3; (C1-C6)alkila, koji je i sam izborno supstituiran s jednim ili više halogena; ili (C1-C6)alkoksi, koji je i sam izborno supstituiran s jednim ili više halogena; -C(O)-(CH2)n-NHRh, gdje je Rh: 6 do 10-eročlani aril, izborno supstituiran s jednim ili više od: halogena; (C1-C6)alkil, koji je i sam izborno supstituiran s jednim ili više halogena; ili (C1-C6)alkoksi, koji je i sam izborno supstituiran s jednim ili više halogena; ili -C(O)-(CH2)n-O-(CH2)n-(6 do 10-eročlani aril); R9 je: vodik; -(CH2)nOH; fenil; -O-(C1-C6)alkil; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; R10 je: vodik; ili (C1-C6)alkil, izborno supstituiran s jednim ili više halogena; i n je 0, 1 ili 2.
9. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što je R9 metil; ili gdje je Rg -C(O)-fenil, -C(O)-CH2-fenil ili -C(O)-NH-fenil; gdje fenil može biti supstituiran s jednim ili više od metila, -CF3 ili halogena.
10. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 8, naznačen time što je: [image] [image] ili njegova farmaceutski prihvatljiva sol, solvat ili stereoizomer.
11. Spoj namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-10, naznačen time što je rak krvi ili koštane srži leukemija ili limfom.
12. Spoj namijenjen upotrebi u skladu s bilo kojim od patentnih zahtjeva 1-10, naznačen time što je rak krvi ili koštane srži multipli mijelom, asimptomatski mijelom ili bezbolni mijelom.
13. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 11, naznačen time što je limfom Hodgkinov limfom.
14. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 11, naznačen time što je limfom nehodgkinovski limfom.
15. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 14, naznačen time što je nehodgkinovski limfom kutani limfom T-stanica, kutani limfom B-stanica, difuzni limfom velikih B-stanica, Waldenstromova makroglobinemija, limfom stanica plašta ili folikularni limfom.
16. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 11, naznačen time što je leukemija kronična limfocitna leukemija, kronična mijelocitna leukemija, akutna limfoblastična leukemija, akutna mijelogena leukemija ili akutna mijeloblastična leukemija.
17. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 1, naznačen time što je rak krvi ili koštane srži prekancerozno stanje, koje se bira iz skupine koju čine mijelodisplastični sindrom i mijeloproliferativna bolest.
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