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SI2887943T1 - Novi 4,6-disubstituirani aminopirimidinski derivati - Google Patents

Novi 4,6-disubstituirani aminopirimidinski derivati Download PDF

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SI2887943T1
SI2887943T1 SI201330960T SI201330960T SI2887943T1 SI 2887943 T1 SI2887943 T1 SI 2887943T1 SI 201330960 T SI201330960 T SI 201330960T SI 201330960 T SI201330960 T SI 201330960T SI 2887943 T1 SI2887943 T1 SI 2887943T1
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methoxy
pyrimidin
ylamino
methoxyphenyl
phenyl
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Franco Lori
Gyorgy Keri
James Chafouleas
Forni Davide De
Antonio Solinas
Zoltan Varga
Zoltan Greff
Laszlo Orfi
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Virostatics Srl Porto Conte Ricerche
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Claims (2)

NOVI 4,6-DISUBSTITUTIRANI AMINOPIRIMIDINSKI DERIVATI PATENTNI ZAHTEVKI
1. Spojina s formulo (I):
(D kjer so X, Y in Z H, F ali Cl; R: je OR, kjer je R vodik ali skupina, izbrana izmed ravnega ali razvejanega C1-C6 alkila, C2-C6 alkenila, C2-C6 alkinila, C3-C6 cikloalkila, heterociklila, CF3, CCI3 in arila v položajih 2, 3 ali 4; R2 je OH, alkoksi, ariloksi, CH2OR (kjer je R H, linearni ali razvejeni aril, cikloalkil ali alkil), CH2NR'R"(kjer sta R' in R" neodvisno H, linearni ali razvejani aril, cikloalkil ali alkil), CHO, OCOW (kjer je W raven ali razvejan aril ali alkil ali C-(halogen)3), CONR'R" (kjer sta R' in R" neodvisno H, alkil, cikloalkil ali aril), COOR (kjer je R H, alkil, cikloalkil ali aril), CH2NHS02R (kjer je R H, alkil, cikloalkil ali aril), Cl, Br, F, CH2-/V-benzimidazol, CONHNR'R"(kjer sta R' in R" neodvisno H, alkil, cikloalkil ali aril), NRCOOR' (kjer sta R in R' neodvisno H, alkil, cikloalkil ali aril), NH2, NR'R"(kjer sta R' in R" neodvisno alkil, cikloalkil ali aril), NHCOR (kjer je R H, alkil, cikloalkil ali aril), nitro, OCH2CH2-heterociklil, OCOR (kjer je R H, alkil, cikloalkil ali aril), OCONR'R" (kjer sta R' in R" neodvisno H, alkil, cikloalkil ali aril), OCOOR (kjer je R je H, alkil, cikloalkil ali aril), NHCOOCH2C-halo3, NRCONR'R" (kjer so R, R' in R" neodvisno H, alkil, cikloalkil ali aril), NHS02R (kjer je R H, alkil, cikloalkil ali aril), NHS02NR'R" (kjer R' in R" neodvisno H, alkil, cikloalkil ali aril),
in R3 je OH, alkoksi, ariloksi, NR'R" (kjer sta R' in R" H), NHCOR (kjer je R H, alkil, cikloalkil ali aril), in_CONR'R" (kjer sta R' in R" neodvisno H, alkil, cikloalkil ali aril).
2. Spojina po zahtevku 1, kjer je Ri OR, kjer je R H, metil, izopropil ali etil.
3. Spojina po zahtevku 1, kjer je Ri 2'-OR, kjer je R H, metil, etil ali izopropil.
4. Spojina po zahtevku 1, kjer je Z H ali F.
5. Spojina po zahtevku 1, kjer je R2 izbran iz skupine, ki jo sestavljajo OH, linearen ali razvejan alkoksi, CH2OR (kjer je R alkil), NH2, CH2NH2, OCOC(CH3)3, CONH2i Cl, Br, CH2-N-benzimidazol, NHS02R (kjer je R alkil ali aril) in NHS02NR’R" (kjer sta R' in R" neodvisno H, alkil ali aril), OCH2CH2-heterociklil, OCOR (kjer je R H, alkil, cikloalkil ali aril), OCONR'R" (kjer sta R' in R" neodvisno H, alkil, cikloalkil ali aril).
6. Spojina po zahtevku 1, kjer je R3 OH, linearni ali razvejani alkoksi, NR'R" (kjer sta R' in R" H), CONR'R" (kjer sta R' in R" neodvisno H, alkil, cikloalkil ali aril).
7. Spojina po zahtevku 1, kjer je R2 izbran iz skupine, ki jo sestavljajo OH, linearni ali razvejani alkoksi, CONH2, OCOC(CH3)3, Cl, CH2-/V-benzimidazol in R3 je izbran iz skupine, ki jo sestavlja alkoksi.
8. Spojina po zahtevku 1, kjer so X, Y in Z H ali F, R2 je linearni ali razvejan alkoksi, CONH2, OCOC(CH3)3, Cl, CH2-A/-benzimidazol in R3 je alkoksi.
9. Spojina po zahtevku 1, kjer so X, Y in Z H ali F, Ri je metoksi ali etoksi, R2 je linearen ali razvejan alkoksi, CONH2, Cl, Br, CH2-/V-benzimidazol in R3 je alkoksi.
10. Spojina po zahtevku 1, kjer sta X in Y 4'-F, 5'-F ali H in Z je 2'-F ali H, Ri je 2'-OR, kjer je R H, metil, etil ali izopropil, R2 je linearni ali razvejan alkoksi, CONH2, Cl, Br, CH2-A/-benzimidazol in R3 je OR' (kjer je R' alkil).
11. Farmacevtski sestavek, ki obsega farmacevtsko sprejemjiv ekscipient razredčilo ali nosilec in terapevtsko učinkovito količino spojine po katerem koli od zahtevkov 1 do 10.
12. Spojina po katerem koli od zahtevkov 1 do 10, izbrana izmed:
2-Metoksi-N4-[6-(2-metoksi-fenil)-pirimidin-4-il]-benzen-1,4-diamin (Primer 59); Metil 2-Metoksi-5-(6-(2-metoksi-fenil)-pirimidin-4-ilamino]-benzoat (Primer 30); N1-[6-(4-Fluoro-2-metoksi-fenil)-pirimidin-4-il]-4-metoksibenzen-1,3-diamin (Primer 64);
4-Fluoro-6-metoksi-N3-[6~(2-metoksi-fenil)-pirimidin-4-il]-benzen-1,3-diamin (Primer 92);
4- Fluoro-5-[6-(5-fluoro-2-metoksi-fenil)-pirimidin-4-ilamino]-2-metoksi-benzamid (Primer 144); 2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)fenil pivalat (Primer 26); 5- [6-(4-Fluoro-2-metoksi-fenil)-pirimidin-4-ilamino]-2-metoksi-fenol (Primer 123); N-(3-(benziloksi)-4-metoksifenil)-6-(2-metoksifenil)-pirimidin-4-amin (Primer 36); N-(3-fluoro-4-metoksifenil)-6-(2-metoksifenil)pirimidin-4-amin (Primer 22); 2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)-fenol (Primer 32); 4-metoksi-N1-(6-(2-metoksifenil)pirimidin-4-il)benzen-1,3-diamin (Primer 41); 2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)benzamid (Primer 45); {2-Metoksi-5-[6-(2-metoksi-fenil)-pirimidin-4-ilamino]-fenil}-karbamska kislina metil ester (Primer 51); (2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)-fenil)(metilsulfamoil)amin (Primer 10); N-benzil-2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)benzamid (Primer 23); (2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)-fenil)metanol (Primer 24); 2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)-N-metilbenzamid (Primer 25); N-(4-metoksi-3-nitrofenil)-6-(2-metoksifenil)pirimidin-4-amin (Primer 11); N1-[6-(2-lzopropoksi-fenil)-pirimidin-4-il]-4-metoksibenzen-1,3-diamin (Primer 79); N-(3-((dimetilamino)metil)-4-metoksifenil)-6-(2-metoksifenil)pirimidin-4-amin (Primer 35); N-(4-metoksi-3-((fenilamino)metil)fenil)-6-(2-metoksifenil)pirimidin-4-amin (Primer 34); 2-(2-metoksi-5-(6-(2-metoksifenil)pirimidin-4-ilamino)-benzil)izoindolin-1,3-dion (Primer 3);
4- Fluoro-5-[6-(4-fluoro-2-metoksi-fenil)-pirimidin-4-ilamino]-2-metoksi-benzamid (Primer 146); 5- [6-(4-Fluoro-2-metoksi-fenil)-pirimidin-4-ilamino]-2-metoksi-benzamid (Primer 128);
4-Fluoro-2-metoksi-5-[6-(2-metoksi-fenil)-pirimidin-4-ilamino]-benzamid (Primer 143); 5-[6-(2-Etoksi-fenil)-pirimidin-4-ilamino]-4-fluoro-2-metoksi-benzamid (Primer 145); 5-[6-(2-Etoksi-4-fluoro-fenil)-pirimidin-4-ilamino]-4-fluoro-2-metoksi-benzamid (Primer 147); 4-(6-(2-metoksifenil)pirimidin-4-ilamino)-2-nitrofenol (Primer 12); N-(3-((benzilamino)metil)-4-metoksifenil)-6-(2-metoksifenil)pirimidin-4-amin (Primer 1); N-(3-(aminometil)-4-metoksifenil)-6-(2-metoksifenil)-pirimidin-4-amin (Primer 43);
3-Fluoro-5-[6-(4-fluoro-2-metoksi-fenil)-pirimidin-4-ilamino]-2-metoksi-benzamid (Primer 138); in
3-Fluoro-5-[6-(5-fluoro-2-metoksi-fenil)-pirimidin-4-ilamino]-2-metoksi-benzamid (Primer 140).
13. Spojina izbrana izmed
2-Dimetilamino-5-[6-(4-fluoro-2-metoksi-fenil)-pirimidin-4-ilamino]-benzamid (Primer 113); 2-(2-kloro-5-(6-(2-metoksifenil)pirimidin-4-ilamino)benzil)izoindolin-1,3-dion (Primer 20); etil 2-kloro-5-(6-(2-metoksifenil)pirimidin-4-ilamino)benzoat (Primer 14); 2-Fluoro-N4-[6-(2-metoksi-fenil)-pirimidin-4-il]-N1,N1-dimetil-benzen-1,4-diamin (Primer 106);
2-Dimetilamino-5-[6-(2-metoksi-fenil)-pirimidin-4-ilamino]-fenol (Primer 108); 2-Dimetilamino-5-[6-(2-metoksi-fenil)-pirimidin-4-ilamino]-benzamid (Primer 109); etil5-(6-(2-metoksifenil)pirimidin-4-ilamino)-2-morfolinobenzoat (Primer 18); 2-kloro-5-(6-(2-metoksifenil)pirimidin>4-ilamino)benzamid (Primer 44); in N-(3-((1 H-benzo[d]imidazol-1 -il)metil)-4-(4-metilpiperazin-1 -il)fenil)-6-(2-metoksifenil)pirimidin-4-amin (Primer 2).
SI201330960T 2012-08-23 2013-08-23 Novi 4,6-disubstituirani aminopirimidinski derivati SI2887943T1 (sl)

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US201261692641P 2012-08-23 2012-08-23
PCT/US2013/056347 WO2014031937A1 (en) 2012-08-23 2013-08-23 Novel 4,6-disubstituted aminopyrimidine derivatives
EP13831626.0A EP2887943B1 (en) 2012-08-23 2013-08-23 Novel 4,6-disubstituted aminopyrimidine derivatives

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ES2786552T3 (es) 2015-09-29 2020-10-13 Bayer Pharma AG Compuestos de sulfondiimina macrocíclicos nuevos
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EP3190103A1 (en) * 2016-01-08 2017-07-12 Rijksuniversiteit Groningen Inhibitors of the pd-1/pd-l1 protein/protein interaction
EP3601253B1 (en) 2017-03-28 2021-09-15 Bayer Aktiengesellschaft Novel ptefb inhibiting macrocyclic compounds
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CN109761909B (zh) * 2019-01-25 2022-08-26 中国药科大学 N-(4-(嘧啶-4-氨基)苯基)磺酰胺类抑制剂或其可药用的盐、其制备方法及用途
IT201900004737A1 (it) 2019-03-29 2020-09-29 Virostatics Srl Composti aventi attività enzimatica anti-CDK4/6 e anti-CDK9 per l’inibizione della proliferazione del cancro e relativi metodi di screening per la loro identificazione.
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