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HRP20161115T1 - Aril- ili heteroaril-supstituirani spojevi benzena - Google Patents

Aril- ili heteroaril-supstituirani spojevi benzena Download PDF

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Publication number
HRP20161115T1
HRP20161115T1 HRP20161115TT HRP20161115T HRP20161115T1 HR P20161115 T1 HRP20161115 T1 HR P20161115T1 HR P20161115T T HRP20161115T T HR P20161115TT HR P20161115 T HRP20161115 T HR P20161115T HR P20161115 T1 HRP20161115 T1 HR P20161115T1
Authority
HR
Croatia
Prior art keywords
image
alkyl
alkylamino
halo
membered heterocycloalkyl
Prior art date
Application number
HRP20161115TT
Other languages
English (en)
Inventor
Kevin Wayne Kuntz
Richard Chesworth
Kenneth William Duncan
Heike KEILHACK
Natalie WARHOLIC
Christine KLAUS
Masashi Seki
Syuji SHIROTORI
Satoshi Kawano
Timothy James Nelson Wigle
Sarah Kathleen Knutson
Original Assignee
Epizyme, Inc.
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.)
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Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=46045109&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=HRP20161115(T1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Epizyme, Inc. filed Critical Epizyme, Inc.
Publication of HRP20161115T1 publication Critical patent/HRP20161115T1/hr

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4412—Non condensed pyridines; Hydrogenated derivatives thereof having oxo groups directly attached to the heterocyclic ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/443—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4433—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with oxygen as a ring hetero atom
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    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4436—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a heterocyclic ring having sulfur as a ring hetero atom
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    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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    • A61K31/445—Non condensed piperidines, e.g. piperocaine
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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
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    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
    • A—HUMAN NECESSITIES
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    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A61K31/553—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having at least one nitrogen and one oxygen as ring hetero atoms, e.g. loxapine, staurosporine
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
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    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
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    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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Claims (16)

1. Spoj s formulom (I) ili njegova farmaceutski prihvatljiva sol: [image] naznačen time da X1 je N ili CR11; X2 je N ili CR13; Z je NR7R8, OR7, S(O)nR7, ili CR7R8R14, gdje n je 0, 1, ili 2; svaki od R1, R5, R9, i R10, neovisno, je H ili C1-C6 alkil proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)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 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril; svaki od R2, R3, i R4, neovisno, je -Q1-T1, gdje Q1 je veza ili C1-C3 alkil poveznica proizvoljno supstituirana s halo, cijano, hidroksil ili C1-C6 alkoksi, i T1 je H, halo, hidroksil, COOH, cijano, ili RS1, gdje RS1 je C1-C3 alkil, C2-C6 alkenil, C2-C6 alkinil, C1-C6 alkoksil, C(O)O-C1-C6 alkil, C3-C8 cikloalkil, C6- C10 aril, amino, mono-C1-C6 alkilamino, di-C1-C6alkilamino, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i RS1 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, okso, COOH, C(O)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 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril; R6 je C6-C10 aril ili 5- ili 6-člani heteroaril, svaki od kojih je proizvoljno supstituiran s jednim ili više -Q2-T2, pri čemu Q2 je veza ili C1-C3 alkil poveznica proizvoljno supstituirana s halo, cijano, hidroksil ili C1-C6 alkoksi, i T2 je H, halo, cijano, -ORa, -NRaRb, -(NRaRbRC)+A-,-C(O)Ra, -C(O)ORa, - C(O)NRaRb, -NRbC(O)Ra, -NRbC(O)ORa, -S(O)2Ra, -S(O)2NRaRb, ili Rs2, gdje svaki od Ra, Rb, i RC, neovisno je H ili RS3, A- je farmaceutski prihvatljiv anion, svaki od RS2 i RS3, neovisno, je C1-C6 alkil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, ili Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 12-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatni heteroatom, i svaki od RS2, RS3, te 4 do 12-člani heterocikloalkilni prsten koji tvore Ra i Rb, je proizvoljno supstituiran s jednim ili više -Q3-T3, pri čemu Q3 je veza ili C1-C3 alkil poveznica svaki proizvoljno supstituiran s halo, cijano, hidroksil ili C1-C6 alkoksi, i T3 se bira iz skupine koju čine halo, cijano, C1-C6 alkil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, 5- ili 6-člani heteroaril, ORd, COORd, -S(O)2Rd, -NRdRe, i -C(O)NRdRe, svaki od R i Re neovisno je H ili C1-C6 alkil, ili -Q3-T3 je okso; ili bilo koja dva susjedna -Q2-T2, zajedno s atomima na koje su oni vezani tvore 5- ili 6-člani prsten koji proizvoljno sadrži 1-4 heteroatoma koji se biraju od N, O i S i proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)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 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril; R7 je -Q4-T4, gdje Q4 je veza, C1-C4 alkil poveznica, ili C2-C4 alkenil poveznica, svaki poveznica proizvoljno supstituirana s halo, cijano, hidroksil ili C1-C6 alkoksi, i T4 je H, halo, cijano, NRfRg, -ORf, -C(O)Rf, -C(O)ORf, - C(O)NRfRg, -C(O)NRfORg, -NRfC(O)Rg, -S(O)2Rf, ili Rs4, gdje svaki od Rf i Rg, neovisno je H ili RS5, svaki od RS4 i RS5, neovisno je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i svaki od RS4 i RS5 je proizvoljno supstituiran s jednim ili više -Q5-T5, pri čemu Q5 je veza, C(O), C(O)NRk, NRkC(O), S(O)2, ili C1-C3 alkil poveznica, Rk je H ili C1-C6 alkil, i T5 je H, halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, 5- ili 6-člani heteroaril, ili S(O)qRq gdje q je 0, 1, ili 2 i Rq je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12- člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i T5 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, te 5- ili 6-člani heteroaril osim kada T5 je H, halo, hidroksil, ili cijano; ili -Q5-T5 je okso; svaki od R8, R11, R12, i R13, neovisno, je H, halo, hidroksil, COOH, cijano, RS6, ORS6, ili COORS6, gdje RS6 je C1-C6 alkil, C2-C6 alkenil, C2-C6 alkinil, C3-C8 cikloalkil, 4 do 12-člani heterocikloalkil, amino, mono-C1-C6 alkilamino, ili di-C1-C6 alkilamino, i RS6 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)O-C1-C6 alkil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, i di-C1-C6 alkilamino; ili R7 i R8, zajedno s atomom N na koji su oni spojeni, tvore 4 do 11-člani heterocikloalkilni prsten koji ima 0 to 2 dodatnih heteroatoma, ili R7 i R8, zajedno s atomom C na koji su oni vezani, tvore C3- C8 cikloalkil ili 4 do 11-člani heterocikloalkilni prsten koji ima 1 do 3 heteroatoma, te svaki od 4 do 11-članih heterocikloalkilnih prstena ili C3-C8 cikloalkil koji tvore R7 i R8 je proizvoljno supstituiran s jednim ili više -Q6-T6, pri čemu Q6 je veza, C(O), C(O)NRm, NRmC(O), S(O)2, ili C1-C3 alkil poveznica, Rm je H ili C1-C6 alkil, i T6 je H, halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, 5- ili 6-člani heteroaril, ili S(O)pRp gdje p je 0, 1, ili 2 i Rp je C1-C6 alkil, C2-C6 alkenil, C2- C6 alkinil, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, ili 5- ili 6-člani heteroaril, i T6 je proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, C1-C6 alkil, hidroksil, cijano, C1-C6 alkoksil, amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C3-C8 cikloalkil, C6-C10 aril, 4 do 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril osim kada T6 je H, halo, hidroksil, ili cijano; ili -Q6-T6 je okso; i R14 je odsutan, H, ili C1-C6 alkil proizvoljno supstituiran s jednim ili više supstituenata koji se biraju iz skupine koju čine halo, hidroksil, COOH, C(O)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 12-člani heterocikloalkil, i 5- ili 6-člani heteroaril.
2. Spoj prema zahtjevu 1, naznačen time da R6 je fenil supstituiran s jednim ili više -Q2- T2; ili Rs je 5- ili 6-člani heteroaril koji sadrži 1-3 dodatnih heteroatoma koji se biraju od N, O, i S i proizvoljno supstituiran s jednim ili više -Q2-T2, poželjno 5- ili 6-člani heteroaril je piridinil, pirazolil, pirimidinil, kinolinil, tetrazolil, oksazolil, izoksazolil, tiazolil, izotiazolil, furil, ili tienil, svaki od kojih je proizvoljno supstituiran s jednim ili više -Q2-T2.
3. Spoj prema bilo kojem od zahtjeva 1-2, naznačen time da T2 je -NRaRb ili - C(O)NRaRb, gdje svaki od Ra i Rb, neovisno je H ili C1-C6 alkil, ili Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 12-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatni heteroatom, C1-C6 alkil i 4 do 12-člani heterocikloalkilni prsten koji je proizvoljno supstituiran s jednim ili više -Q3-T3, i Q2 je C1-C3 alkil poveznica proizvoljno supstituirana s halo ili hidroksilom.
4. Spoj prema bilo kojem od zahtjeva 1-3, naznačen time da R7 je C1-C6 alkil, C3-C8 cikloalkil ili 4 do 12-člani heterocikloalkil, svaki proizvoljno supstituiran s jednim ili više -Q5-T5; ili R7 je 4 do 12-člani heterocikloalkil proizvoljno supstituiran s jednim ili više -Q5-T5, poželjno R7 je piperidinil, tetrahidropiran, tetrahidro-2H- tiopiranil,ciklopentil, ili cikloheksil, svaki proizvoljno supstituiran s jednim ili više -Q5-T5.
5. Spoj prema bilo kojem od zahtjeva 1-4, naznačen time da (i) jedan ili više -Q5-T5 su okso; ili (ii) T5 je H, halo, C1-C6 alkil, C1-C6 alkoksil, C3-C8 cikloalkil, C6-C10 aril, ili 4 do 12-člani heterocikloalkil; ili (iii) kada Q5 je veza, T5 je amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, C1-C6 alkil, C3-C8 cikloalkil, ili 4 do 12-člani heterocikloalkil; ili (iv) kada Q5 je CO, S(O)2, ili NHC(O), T5 je C1-C6 alkil, C1-C6 alkoksil, C3-C8 cikloalkil, ili 4 do 12-člani heterocikloalkil; ili (v) kada Q5 je C1-C3 alkil poveznica, T5 je H, C6-C10 aril, C3-C8 cikloalkil, 4 do 12-člani heterocikloalkil, ili S(O)qRq.
6. Spoj prema bilo kojem od zahtjeva 1-5, naznačen time da svaki od R1 i R11 je H.
7. Spoj prema bilo kojem od zahtjeva 1-6, naznačen time da svaki od R2 i R4, neovisno je H ili C1-C6 alkil proizvoljno supstituiran s amino, mono-C1-C6 alkilamino, di-C1-C6 alkilamino, ili C6-C10 aril, poželjno svaki od R2 i R4 je metil.
8. Spoj prema bilo kojem od zahtjeva 1-7, naznačen time da R12 je H, metil, etil, etenil, ili halo, R8is H, metil, ili etil, i R13 je H ili metil.
9. Spoj prema zahtjevu 1, naznačen time da spoj ima Formulu (Ie): [image] poželjno spoj ima Formulu (Ig): [image] pri čemu R2, R4 i R12 su svaki, neovisno C1-6 alkil.
10. Spoj prema bilo kojem od zahtjeva 1 i 9, naznačen time da R6 je C6-C10 aril ili 5- ili 6- člani heteroaril, svaki od kojih je proizvoljno, neovisno supstituiran s jednim ili više - Q2-T2, pri čemu Q2 je veza ili C1-C3 alkil poveznica, i T2 je H, halo, cijano, -ORa, - NRaRb, - (NRaRbRC)+A-, -C(O)NRaRb, -NRbC(O)Ra, -S(O)2R, ili Rs2, gdje svaki od Ra i Rb, neovisno je H ili RS3, svaki od RS2 i RS3, neovisno, je C1-C6 alkil, ili Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 7-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatni heteroatom, i svaki od RS2, RS3, i 4 do 7-člani heterocikloalkilni prsten koji tvore Ra i Rb, je proizvoljno, neovisno supstituiran s jednim ili više -Q3-T3, pri čemu Q3 je veza ili C1-C3 alkil poveznica i T3 se bira iz skupine koju čine halo, C1-C6 alkil, 4 do 7-člani heterocikloalkil, ORd, -S(O)2Rd, i - NRdRe, svaki od R i Re neovisno je H ili C1-C6 alkil, ili -Q3-T3 je okso; ili bilo koja dva susjedna -Q2-T2, zajedno s atomima na koje su oni vezani tvore 5- ili 6-člani prsten koji proizvoljno sadrži 1-4 heteroatoma koji se biraju od N, O i S.
11. Spoj prema bilo kojem od zahtjeva 1 i 9, naznačen time da spoj ima Formulu (II): [image] pri čemu Q2 je veza ili metil poveznica,T2 je H, halo, -ORa, -NRaRb, -(NRaRbRC)+A- ili -S(O)2NRaRb, R7 je piperidinil, tetrahidropiran, ciklopentil, ili cikloheksil, svaki proizvoljno supstituiran s one -Q5-T5 i R8 je etil, poželjno spoj ima Formulu (IIa): [image]
12. Spoj prema bilo kojem od zahtjeva 1, 9, i 11, naznačen time da (i) svaki od Ra i Rb, neovisno je H ili C1-C6 alkil proizvoljno supstituiran s jednim ili više -Q3-T3, (ii) jedan od Ra i Rb je H, ili (iii) Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore 4 do 7-člani heterocikloalkilni prsten koji ima 0 ili 1 dodatnih heteroatoma na atomu N i prsten je proizvoljno supstituiran s jednim ili više -Q3-T3, poželjno Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore azetidinil, pirolidinil, imidazolidinil, pirazolidinil, oksazolidinil, izoksazolidinil, triazolidinil, tetrahidrofuranil, piperidinil, 1,2,3,6-tetrahidropiridinil, piperazinil, ili morfolinil, i prsten je proizvoljno supstituiran s jednim ili više -Q3-T3, i više poželjno Ra i Rb, zajedno s atomom N na koji su oni spojeni, tvore morfolinil.
13. Spoj prema zahtjevu 1, naznačen time da spoj je odabran od [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] [image] [image] [image] [image] [image] [image] i njihove farmaceutski prihvatljive soli, te je poželjno spoj odabran od [image] [image] [image] [image] [image] [image] [image] i njihove farmaceutski prihvatljive soli.
14. Spoj prema zahtjevu 1, naznačen time da spoj je [image] ili njegova farmaceutski prihvatljiva sol.
15. Farmaceutski pripravak naznačen time da sadrži spoj prema bilo kojem od zahtjeva 114 ili njegovu farmaceutski prihvatljivu sol i farmaceutski prihvatljiv nosač.
16. Spoj prema bilo kojem od zahtjeva 1-14 naznačen time da je za upotrebu u postupku liječenja ili sprječavanja raka.
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CA2832843A1 (en) 2012-10-18
SG194447A1 (en) 2013-12-30
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