HRP20231155T1 - Modulatori 5'-nukleotidaze, ecto i njihova uporaba - Google Patents

Modulatori 5'-nukleotidaze, ecto i njihova uporaba Download PDF

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Publication number
HRP20231155T1
HRP20231155T1 HRP20231155TT HRP20231155T HRP20231155T1 HR P20231155 T1 HRP20231155 T1 HR P20231155T1 HR P20231155T T HRP20231155T T HR P20231155TT HR P20231155 T HRP20231155 T HR P20231155T HR P20231155 T1 HRP20231155 T1 HR P20231155T1
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Croatia
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HRP20231155TT
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Laurent Pierre Paul Debien
Juan Carlos Jaen
Jaroslaw Kalisiak
Kenneth V. LAWSON
Manmohan Reddy Leleti
Erick Allen Lindsey
Dillon Harding MILES
Eric NEWCOMB
Jay Patrick POWERS
Brandon Reid ROSEN
Ehesan Ui SHARIF
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Arcus Biosciences, Inc.
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Publication of HRP20231155T1 publication Critical patent/HRP20231155T1/hr

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Claims (20)

1. Spoj, naznačen time, da ima sljedeću formulu: [image] ili njegova farmaceutski prihvatljiva sol, njegov hidrat ili solvat, gdje, svaki R1 se neovisno bira iz skupine koju čine vodik, opcionalno supstituirani C1-C6 alkil, opcionalno supstituirani aril, i -C(R2R2)-O-C(O)-OR3, ili se dvije skupine R1 opcionalno kombiniraju u svrhu tvorbe 5-članog do 7-članog prstena; svaki R2 se neovisno bira iz skupine koju čine H, i opcionalno supstituirani C1-C6 alkil; svaki R3 se neovisno bira iz skupine koju čine H, C1-C6 alkil, i opcionalno supstituirani aril; R5 se bira iz skupine koju čine H i opcionalno supstituirani C1-C6 alkil; X se bira iz skupine koju čine O, CH2, i S; A se bira iz skupine koju čine: [image] [image] od kojih je svaki opcionalno supstituiran s 1 do 5 supstituenata R6, i pritom je donji indeks n cijeli broj od 0 do 3; Z se bira iz skupine koju čine O, CH2, CHR6i NR6; svaki R6 se neovisno bira iz skupine koju čine OH, H, CH3, CN, F, opcionalno supstituirani C1-C6 alkil, i OC(O)-C1-C6 alkil; i opcionalno su dvije R6 skupine na susjednim najvišim točkama prstena spojene zajedno u svrhu tvorbe 5-članog do 6-članog prstena koji ima najmanje jedan heteroatom kao najvišu točku prstena; i Het se bira iz skupine koju čine: [image] gdje valovita linija označava točku vezanja s ostatkom spoja, i pri čemu: Ra se bira iz skupine koju čine H, NH2, NHR7, NHC(O)R7, NR7R7, R7, OH, SR7, i OR7; Rb se bira iz skupine koju čine H, halogen, NH2, NHR7, NR7R7, R7, OH, i OR7; Rc se bira iz skupine koju čine H, halogen, haloalkil, NH2, NHR7, NR7R7, R7, OH, OR7, SR7, SO2R7, -X1-NH2, -X1-NHR7, -X1-NR7R7, -X1-OH, -X1-OR7, -X1-SR7, i -X1-SO2R7; Re se bira iz skupine koju čine H, halogen, i opcionalno supstituirani C1-C6 alkil; svaki X1 je C1-C4 alkilen; i svaki R7 se neovisno bira iz skupine koju čine opcionalno supstituirani C1-C10 alkil, opcionalno supstituirani C2-C10 alkenil, opcionalno supstituirani C2-C10 alkinil, opcionalno supstituirani C3-C7 cikloalkil, opcionalno supstituirani C3-C7 cikloalkilC1-C4 alkil,opcionalno supstituirani 4-7-člani cikloheteroalkil, opcionalno supstituirani 4-7-člani cikloheteroalkilC1-C4 alkil, opcionalno supstituirani aril, opcionalno supstituirani arilC1-C4 alkil, opcionalno supstituirani arilC2-C4 alkenil, opcionalno supstituirani arilC2-C4 alkinil, opcionalno supstituirani heteroaril, opcionalno supstituirani heteroarilC1-C4 alkil, opcionalno supstituirani heteroarilC1-C4 alkenil, opcionalno supstituirani heteroarilC2-C4 alkinil, i opcionalno, dvije skupine R7 koje su vezane s dušikovim atomom, spajaju se zajedno u svrhu tvorbe 4-članog do 7-članog heterocikličkog prstena, opcionalno staljenog na arilni prsten.
2. Spoj prema patentnom zahtjevu 1, naznačen time, da A je: [image] koji je opcionalno supstituiran s 1 do 5 R6; opcionalno pritom se A bira iz skupine koju čine: [image] [image] .
3. Spoj prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da R5 je H, X je O, i svaki R1 je H.
4. Spoj prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da R5 je H, X je O, svaki R1 je H, Re je H, i Ra se bira iz skupine koju čine NH2, NHR7, i N(R7)2.
5. Spoj prema patentnom zahtjevu 1 ili zahtjevu 2, naznačen time, da R5 je H, X je O, svaki R1 je H, Re je H, Rc je različit od H, i Ra je NHR7.
6. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time, da HET je [image]
7. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time, da HET je [image]
8. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5, naznačen time, da Het-A je [image] ili [image]
9. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5 ili 8, naznačen time, da Rc je halogen.
10. Spoj prema bilo kojem od patentnih zahtjeva 1 do 5 ili 8, naznačen time, da Ra je NHR7.
11. Spoj prema patentnom zahtjevu 1, naznačen time, da se bira od sljedećih: [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] [image] i [image] ili njegova farmaceutski prihvatljiva sol, njegov hidrat ili solvat.
12. Spoj prema patentnom zahtjevu 1, naznačen time, da je: [image] ili [image] ili [image] ili [image] ili njegova farmaceutski prihvatljiva sol, njegov hidrat ili solvat.
13. Spoj prema patentnom zahtjevu 1, naznačen time, da je [image] ili njegova farmaceutski prihvatljiva sol.
14. Farmaceutski pripravak, naznačen time, da sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 13 ili njegovu farmaceutski prihvatljivu sol, njegov hidrat ili solvat, i farmaceutski prihvatljivo pomoćno sredstvo.
15. Spoj prema bilo kojem od patentnih zahtjeva 1 do 13, ili njegova farmaceutski prihvatljiva sol, njegov hidrat ili solvat, naznačen time, da je za uporabu u postupku za liječenje bolesti, poremećaja ili stanja, posredovanih barem djelomično putem CD73; opcionalno pritom: navedeni spoj se daje u količini učinkovitoj za preokretanje ili zaustavljanje progresije CD73-posredovane imunosupresije.
16. Spoj za uporabu prema patentnom zahtjevu 15, naznačen time, da je navedena bolest, poremećaj ili stanje sljedeće: A: rak, primjerice, pri čemu navedeni rak je rak prostate, debelog crijeva, rektuma, gušterače, grlića maternice, abdomena, endometrija, mozga, jetre, mokraćnog mjehura, jajnika, testisa, glave, vrata, kože (uključujući melanom i bazalni karcinom), mezotelnih slojeva, bijelih krvnih stanica (uključujući limfom i leukemiju), jednjaka, dojke, mišića, vezivnog tkiva, pluća (uključujući karcinom pluća malih stanica i karcinom pluća ne-malih stanica), nadbubrežne žlijezde, štitnjače, bubrega, ili kosti; ili je glioblastom, mezoteliom, karcinom bubrežnih stanica, karcinom želuca, sarkom (uključujući Kaposijev sarkom), horiokarcinom, kožni bazocelularni karcinom, ili seminom testisa; ili pri čemu je navedeni rak odabran iz skupine koju čine melanom, rak debelog crijeva, rak gušterače, rak dojke, rak prostate, rak pluća, leukemija, tumor mozga, limfom, rak jajnika, i Kaposijev sarkom; ili B: imunološki odnosni bolest, poremećaj ili stanje, odabrani iz skupine koju čine reumatoidni artritis, zatajenje bubrega, lupus, astma, psorijaza, kolitis, pankreatitis, alergije, fibroza, fibromialgijska anemija, Alzheimerova bolest, kongestivni srčani zastoj, moždani udar, stenoza aortnih ventila, arterioskleroza, osteoporoza, Parkinsonova bolest, infekcije, Crohnova bolest, ulcerativni kolitis, alergijski kontaktni dermatitis i ostali ekcemi, sistemska skleroza i multipla skleroza.
17. Kombinacija, naznačena time, da sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 13, ili njegovu farmaceutski prihvatljivu sol, njegov hidrat ili solvat, i najmanje jedno dodatno terapijsko sredstvo; opcionalno pritom je najmanje jedno dodatno terapijsko sredstvo: (i) kemoterapeutsko sredstvo, imunomodulacijsko sredstvo i/ili modulacijsko sredstvo za upale, sredstvo protiv hiperkolesterolemije, ili protuzarazno sredstvo; ili (ii) inhibitor imunosne kontrolne točke.
18. Komplet, naznačen time, da sadrži spoj prema bilo kojem od patentnih zahtjeva 1 do 13, ili njegovu farmaceutski prihvatljivu sol, njegov hidrat ili solvat, i najmanje jedno dodatno terapijsko sredstvo; pri čemu opcionalno: (i) najmanje jedno dodatno terapijsko sredstvo je kemoterapeutsko sredstvo, imunomodulacijsko sredstvo i/ili modulacijsko sredstvo za upale, sredstvo protiv hiperkolesterolemije, ili protuzarazno sredstvo; ili (ii) najmanje jedno dodatno terapijsko sredstvo je inhibitor imunosne kontrolne točke.
19. Spoj prema bilo kojem od patentnih zahtjeva 1 do 13, ili njegova farmaceutski prihvatljiva sol, njegov hidrat ili solvat, naznačen time, da je za uporabu u postupku za liječenje raka kod pojedinca, pri čemu spomenuti postupak obuhvaća davanje navedenom pojedincu učinkovite količine spoja i inhibitora imunosne kontrolne točke; opcionalno: (i) pri čemu spomenuto davanje nastupa prije, istovremeno s, ili uzastopno nakon radijacijske obrade; i/ili (ii) pri čemu se navedeni spoj i navedeni inhibitor imunosne kontrolne točke daju u kombinaciji; ili (iii) pri čemu se navedeni spoj i navedeni inhibitor imunosne kontrolne točke daju uzastopno; ili (iv) pri čemu se navedeni spoj daje poslije navedenog inhibitora imunosne kontrolne točke, ili (v) pri čemu se navedeni spoj daje prije navedenog inhibitora imunosne kontrolne točke.
20. Kombinacija, komplet ili spoj za uporabu prema bilo kojem od patentnih zahtjeva 17, 18 ili 19, naznačeni time, da navedeni inhibitor imunosne kontrolne točke: a) inhibira PD-1, PD-L1, ili CTLA-4; ili b) se bira iz skupine koju čine ipilimumab, nivolumab i lambrolizumab.
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JP2019501223A (ja) 2019-01-17
EA201891583A1 (ru) 2019-01-31
BR112018013827A2 (pt) 2018-12-11
IL260260B2 (en) 2024-01-01
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US11001603B2 (en) 2021-05-11
US20170267710A1 (en) 2017-09-21
CN114395005A (zh) 2022-04-26
ES2963759T3 (es) 2024-04-01
AU2017206061B2 (en) 2022-12-15
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EP4306525A3 (en) 2024-03-20
IL260260A (en) 2018-07-31
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PT3399984T (pt) 2023-11-21
TWI744274B (zh) 2021-11-01
MX2018008350A (es) 2019-05-30
CN108697719B (zh) 2024-03-19
SA518391985B1 (ar) 2022-12-19
UA124529C2 (uk) 2021-10-05
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WO2017120508A8 (en) 2018-07-05
ZA202209472B (en) 2023-06-28
JP2021167351A (ja) 2021-10-21
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TW202227095A (zh) 2022-07-16
CL2018001845A1 (es) 2018-12-07
EA038565B1 (ru) 2021-09-15
BR112018013827B1 (pt) 2024-02-20
IL260260B1 (en) 2023-09-01
CA3009196C (en) 2022-05-31
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