ME02420B - 5-supstituirani derivati kinazolinona kao sredstva protiv raka - Google Patents

5-supstituirani derivati kinazolinona kao sredstva protiv raka

Info

Publication number
ME02420B
ME02420B MEP-2016-47A MEP4716A ME02420B ME 02420 B ME02420 B ME 02420B ME P4716 A MEP4716 A ME P4716A ME 02420 B ME02420 B ME 02420B
Authority
ME
Montenegro
Prior art keywords
optionally substituted
alkyl
halogens
hydrogen
compound
Prior art date
Application number
MEP-2016-47A
Other languages
English (en)
Inventor
George W Muller
Hon-Wah Man
Original Assignee
Celgene Corp
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 Celgene Corp filed Critical Celgene Corp
Publication of ME02420B publication Critical patent/ME02420B/me

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    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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Claims (17)

1. Spoj formule (I):,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; ili6 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; in 0, 1 ili 2.
2. Spoj namijenjen upotrebi u skladu s patentnim zahtjevom 1, naznačen time što ima strukturu formule (II): , 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: , , , , , , , , , , , , , , , , 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): , 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: , , , , , , , , , , , , , , , , , , , , , 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): , 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: , , , , , , , , , , , , , , , , , , , , , , , , 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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