ME02202B - Jedinjenja pirolopirimidina kao inhibitori cdk4/6 - Google Patents

Jedinjenja pirolopirimidina kao inhibitori cdk4/6

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Publication number
ME02202B
ME02202B MEP-2015-157A MEP15715A ME02202B ME 02202 B ME02202 B ME 02202B ME P15715 A MEP15715 A ME P15715A ME 02202 B ME02202 B ME 02202B
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Montenegro
Prior art keywords
pyridin
pyrrolo
ylamino
diaza
cyclopentyl
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MEP-2015-157A
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English (en)
Inventor
Yaping Wang
Christopher Thomas Brain
Young Shin Cho
John William Giraldes
Bharat Lagu
Julian Levell
Michael LUZZIO
Lawrence Blas Perez
Fan Yang
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Novartis Ag
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Publication of ME02202B publication Critical patent/ME02202B/me

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    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/10—Spiro-condensed systems
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
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    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Saccharide Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (25)

1. Jedinjenje prema formuli (I)naznačen time, što:R1 predstavlja C3-7alkil; C4-7 cikloalkil po slobodnom izboru supstituisan sa jednim ili više supstituenta koji su odabrani iz grupe koju čine C1-6alkil i OH; fenil po slobodnom izboru supstituisan jednim supstitutentom koji je odabran iz grupe koju čine C1-6 alkil, C(CH3)2CN, i OH; piperidinil po slobodnom izboru supstituisan sa jednom ciklopropil grupom ili C1-6 alkilom; tetrahidropiranil po slobodnom izboru supstituisan sa jednom ciklopropil grupom ili C1-6 alkilom; ili biciklo[2.2.1]heptanil;gde A predstavlja CH ili N;gde R11 predstavlja vodonik ili C1-4 alkil;gde L predstavlja vezu, C(O), ili S(O)2;gde R2Y može da bude izabran iz grupe koju čineV je NH ili CH2;X je O ili CH2;W je O ili NH;gde m i n svaki za sebe predstavljaju 1, 2, ili 3 pod uslovom da m i n nisu oba 3;gde je svaka R2Y po slobodnom izboru supstituisana sa jednim do četiri supstituenata od kojih je svaki nezavisno odabran iz grupe koju čine: C1-3 alkil po slobodnom izboru substituisan sa jednim ili dva supstituenta od kojih je svaki nezavisno odabran iz grupe koju čine hidroksi, NH2, i -S-C1-3alkil; CD3; halo; okso; C1-3 haloalkil; hidroksi; NH2; dimetilamino; benzil; -C(O)-C1-3alkil po slobodnom izboru supstituisan sa jednim ili dva supstituenta od kojih je svaki odabran iz grupe koju čine NH2’ -SCH3 i NHC(O)CH3; - S(O)2-C1-4 alkil; i pirolidinil-C(O)-;gde R4 predstavlja, vodonik, deuterijum, ili C(R5)(R6)(R7); igde R5, R6, R7, R8, R9 i R10 svaki za sebe nezavisno predstavljaju H ili deuterijum; ili njena farmaceutski prihvatljiva so.
2.Jedinjenje formule (I-B) prema patentnom zahtevu 1, naznačen time, što L predstavlja vezu ili C(O); gde R2Y može da bude izabran iz grupe koju čine V je NH ili CH2; X je O ili CH2; W je O ili NH; gde m i n svaki za sebe nezavisno mogu da budu 1, 2, ili 3 pod uslovom da m i n m i n nisu oba 3; gde je svaka R2Y po slobodnom izboru supstituisana sa jednim do četiri supstituenata od kojih je svaki odabran iz grupe koju čine: C1-3 alkil po slobodnom izboru substituisan sa jednim ili dva supstituenta od kojih je svaki nezavisno odabran iz grupe koju čine hidroksi, NH2, i -S-C1-3alkil; CD3; C1-3 haloalkil; hidroksi; NH2; dimetilamino; benzil; -C(O)-C1-3alkil po slobodnom izboru supstituisan sa jednim ili dva supstituenta od kojih je svaki odabran iz grupe koju čine NH2’ -SCH3 i NHC(O)CH3; - S(O)2-C1-4 alkil; i pirolidinil-C(O)-; ili njena farmaceutski prihvatljiva so.
3. Jedinjenje prema bilo kojem od predhodnih patentnih zahteva, naznačen time, što A predstavlja CH i R11 je vodonik; ili njena farmaceutski prihvatljiva so.
4. Jedinjenje prema bilo kojem od predhodnih patentnih zahteva, naznačen time, što R4 predstavlja C(R5)(R6)(R7) i R5, R6, R7, R8, R9 i R10 mogu da predstavljaju vodonik, ili njenu farmaceutski prihvatljivu so.
5. Jedinjenje prema bilo kojem od predhodnih patentnih zahteva, naznačen time, što R1 predstavlja C4-7 cikloalkil koji je po slobodnom izboru supstituisan jednom C1-6 alkil grupom, ili njena farmaceutski prihvatljiva so.
6. Jedinjenje prema bilo kojem od predhodnih patentnih zahteva, naznačen time, što je R2Y nesupstituisana ili njena farmaceutski prihvatljiva so.
7. Jedinjenje prema bilo kojem od patentnih zahteva 1-5 naznačen time, što R2Y predstavlja ili od kojih je bilo koja po slobodnom izboru supstituisana C1-3alkilom, ili njena farmaceutski prihvatljiva so.
8. Jedinjenje prema bilo kojem od patentnih zahteva 1-5 naznačen time, što R2Y predstavlja koja je po slobodnom izboru supstituisana C1-3 alkilom, ili njena farmaceutski prihvatljiva so.
9. Jedinjenje formule (I-C) u kojoj: R1 predstavlja ciklobutil, ciklopentil, cikloheksil, cikloheptil, gde je svaka od njih po slobodnom izboru supstituisana sa jednom metil,etil, ili OH; gde A predstavlja CH ili N; L može da predstavlja vezu, -C(O)-, ili S(O)2-; gde R2Y može da bude jedna iz grupe koju čine ili gde je svaka R2Y po slobodnom izboru supstituisana jednim ili dva supstituenta koji su nezavisno odabrani iz grupe koju čine halogen, metil, etil, ili okso; gde V predstavlja NH ili CH2; gde R4 predstavlja vodonik, deuterijum, ili C(R5)(R6)(R7); i R5, R6, R7, R8, R9 i R10 svaki za sebe nezavisno predstavljaju H ili deuterijum; ili njena ili njena farmaceutski prihvatljiva so.
10. Jedinjenje prema patentnom zahtevu 9, naznačen time, što A predstavlja CH; ili njena farmaceutski prihvatljiva so.
11. Jedinjenje prema patentnom zahtevu 10 naznačen time, što L predstavlja vezu ili -C(O)- i gde R4 predstavlja CH3; i R8, R9 i R10 mogu da budu H; ili njena farmaceutski prihvatljiva so.
12. Jedinjenje prema patentnom zahtevu 11 naznačen time, što R1 predstavlja ciklopentil; ili njena farmaceutski prihvatljiva so.
13. Jedinjenje prema patentnom zahtevu 1, naznačen time, što može biti odabrano iz grupe koju čine: 2-(5-(2,6-Diazaspiro[3.3]heptan-2-karbonil)piridin-2-ilamino)-7-ciklopentil-N,N-dimetil-7H-pirolo[2,3-d]pirimidin-6-karboksamid; dimetilamid 7-(4-terc-Butil-fenil)-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-(4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6- karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-((1R,6S)-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6- karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Cikloheptil-2-[5-(2,5-diaza-biciklo[2.2.1]heptan-2-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-8-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; 2-(5-(2,7-diazaspiro[3.5]nonan-7-karbonil)piridin-2-ilamino)-7-cikloheptil-N,N-dimetil-7H-pirolo[2,3-d]pirimidin-6-karboksamid; dimetilamid 7-ciklopentil-2-[5-(8-metil-3,8-diaza-biciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; metilamid 7-Ciklopentil-2-[5-((S,S)-2,5-diaza-biciklo[2.2.1]heptan-2-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-(3-terc-Butil-fenil)-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; 2-(5-((1R,5S)-3-oksa-7,9-diazabiciklo[3.3.1]nonan-9-karbonil)piridin-2-ilamino)-7-ciklopentil-N,N-dimetil-7H-pirolo[2,3-d]pirimidin-6-karboksamid; dimetilamid 7-[4-(Cijano-dimetil-metil)-fenil]-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-8-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-((1S,6R)-3,9-diaza-biciklo[4.2.1]nonan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-((1R,6S)-3,9-diaza-biciklo[4.2.1]nonan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-(3,6-diaza-biciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; 7-ciklopentil-N,N-dimetil-2-(5-(5’-okso-8-azaspiro[biciklo[3.2.1]oktan-3,3’-pirolidin]-1’-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; dimetilamid 7-Ciklopentil-2[5-(1-okso-heksahidro-pirolo[1,2-a]pirazin-2-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; 7-ciklopentil-N,N-dimetil-2-(5-(2-okso-1-oksa-3,8-diazaspiro[4.5]dekan-3-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; dimetilamid 7-Ciklopentil-2-[5-((1S,6R)-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 2-[5-(4-Okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7-fenil-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; i 7-cikloheksil-N,N-dimetil-2-(5-(4-okso-3,9-diazabiciklo[4.2.1]nonan-3-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; ili njena farmaceutski prihvatljiva so.
14. Jedinjenje prema patentnom zahtevu 1, naznačen time, što može biti odabrano iz grupe koju čine: dimetilamid 7-Ciklopentil-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline dimetilamid 7-Ciklopentil-2-[5-((S,S)-2,5-diaza-biciklo[2.2.1]heptan-2-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6- karboksilne kiseline dimetilamid 7-Ciklopentil-2-[5-((1R,6S)-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline dimetilamid 7-Ciklopentil-2-[5-((1S,5S)-3,6-diaza-biciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklobutil-2-[5-((1S,6R)-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline dimetilamid 7-Cikloheksil-2-[5-((1R,6S)-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)- piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline dimetilamid 7-Ciklopentil-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-3-karbonil)-6-metil-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-(3,8-diaza-biciklo[3.2.1]oktan-3-karbonil)-4-metil-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; dimetilamid 7-Ciklopentil-2-[5-(3,9-diaza-biciklo[3.3.1]nonan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; 7-ciklopentil-N,N-dimetil-2-(5-(3-okso-1,4-diazabiciklo[3.2.2]nonan-4-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-((1R,6S)-9-metil-4-okso-3,9-diazabiciklo[4.2.1]nonan -3-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-((3aS,6aR)-1-oksoheksahidropirolo[3,4-c]pirol-2(1H)-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-((3aR,6aS)-1-oksoheksahidropirolo[3,4-c]pirol-2(1H)-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-cikloheptil-N,N-dimetil-2-(5-(cis-6-oksotetrahidro-1H-pirolo[3,4-c]piridin-5(6H,7H,7aH)-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-(cis-6-oksotetrahidro-1H-pirolo[3,4-c]piridin-5(6H,7H,7aH)-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-((3aR,6aS)-5-metil-1-oksoheksahidropirolo[3,4-c]pirol-2(1H)-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-((1R,3r,5S)-2’-okso-8-azaspiro[biciklo[3.2.1]oktan-3,5’-oksazolidin]-3’-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-(2-okso-1-oksa-3,8-diazaspiro[4.6]undekan-3-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamid; 7-ciklopentil-N,N-dimetil-2-(5-(2-okso-1-oksa-3,7-diazaspiro[4.5]dekan-3-il)piridin-2-ilamino)-7H-pirolo[2,3-d]pirimidin-6-karboksamide; dimetilamid 7-Ciklopentil-2-[5-((S)-2-okso-1-oksa-3,7-diaza-spiro[4.5]dec-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; i dimetilamid 7-Ciklopentil-2-[5-((R)-2-okso-1-oksa-3,7-diaza-spiro[4.5]dec-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline; ili njena farmaceutski prihvatljiva so.
15. Jedinjenje prema patentnom zahtevu 1, naznačen time, što 7-ciklopentil-N,N-dimetil-2-(5-((1R,6S)-9-metil-4-okso-3,9-diazabiciklo[4.2.1]nonan-3-il)piridin-2-ilamino)-7H-pirolo[2,32,3-d]pirimidin-6-karboksamid ima sledeću formulu: ili njena farmaceutski prihvatljiva so.
16. Jedinjenje prema patentnom zahtevu 1, naznačen time, što dimetilamid 7-Ciklopentil-2-[5-(3,8-diazabiciklo[3.2.1]oktan-3-karbonil)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline ima sledeću formulu: ili njena farmaceutski prihvatljiva so.
17. Jedinjenje prema patentnom zahtevu 1, naznačen time, što dimetilamid 7-Ciklopentil-2-[5-((1R,6S)-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline ima sledeću formulu ili njena farmaceutski prihvatljiva so.
18. Jedinjenje prema patentnom zahtevu 1, naznačen time, što metilamid 7-Ciklopentil-2-[5-((1R,6S)-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6-karboksilne kiseline ima sledeću formulu: ili njena farmaceutski prihvatljiva so.
19. Jedinjenje prema patentnom zahtevu 1, naznačen time, što metilamid 7-ciklopentil-2-[5-((1R,6S)-9-metil-4-okso-3,9-diaza-biciklo[4.2.1]non-3-il)-piridin-2-ilamino]-7H-pirolo[2,3-d]pirimidin-6- karboksilne kiseline ima sledeću formulu: ili njena farmaceutski prihvatljiva so.
20. Farmaceutska kompozicija koja obuhvata jedinjenje prema bilo kojem od predhodnih patentnih zahteva, ili njena farmaceutski prihvatljiva so, i farmaceutski prihvatljivi nosač ili ekscipijent.
21. Jedinjenje prema patentnom zahtevu 1 ili 9, za upotrebu u medicini.
22. .Jedinjenje prema patentnom zahtevu 1 ili 9, za upotrebu u lečenju raka.
23. Jedinjenje prema patentnom zahtevu 1 ili 9, za upotrebu u lečenju raka, naznačen time, što je odabrano iz grupe koju čine: mantle ćelijski limfom, multipli mijelom, rak dojke, ezofagealni kancer skvamoznih ćelija, liposarkom, T-ćelijski limfom, melanom, nesitnoćelijski rak pluća i rak pankreasa, folikularni karcinom štitaste žlezde, tumor mezenhimalnog porekla, fibrosarkom, rabdomiosarkom, tumor centralnog ili perifernog nervnog sistema, astrocitom, neuroblastom, gliom, švanom, melanom, seminom, teratokarcinom, osteosarkom, kseroderma pigmentozum, retinoblastom, keratoakatantom, i Kapošijev sarkom, karcinom bešike, dojke, debelog creva, bubrega, epidermis, jetre, pluća, ezofagusa (jednjaka), žučne kese, karcinom jajnika, pankreasa, stomaka, cerviksa, štitne žlezde, nosa, glave i jezika, prostate, i kože, leukemija, akutna limfocitna leukaemija, hronična limfocitna leukaemija, B-ćelijski limfom, difuzni krupnoćelijski B limfom, T-ćelijski limfom, Hodžkinov limfom, ne Hodžkinov limfom, limfom vlasastih ćelija, i Burkitov limfom, glioblastom multiforme, T ćelijski ALL, sarkomi i familijarni melanom.
24. Upotreba jedinjenja prema patentnom zahtevu 1 u proizvodnji leka za lečenje raka.
25. Jedinjenje formule (I) prema patentnom zahtevu 1, ili njena farmaceutski prihvatljiva so u kombinaciji sa jednim ili više drugih terapijskih sredstava za simultanu, odvojenu ili sekvencijalnu upotrebu u terapiji. EP 2 536 730 B1 REFERENCE KOJE SU NAVEDENE U OPISU Popis literature od strane podnosioca služi samo kao priručnik za čitaoca. Priručnik nije deo Evropske patent dokumentacije. Iako se posvećuje velika pažnja prevodu referenci, greške i propusti ne mogu biti izuzeti i EPO se odriče svake odgovornosti u tom smislu • WO 2007140222 A [0006] • WO 2009085185 A [0006] • WO 2008135232 A [0006] • US 20090203688 A [0006] • WO 2010020675 A [0134] [0267] [0274] • WO 2009067108 W [0260] • WO 2005097791 W [0279] • WO 2007040282 A [0303] • WO 2006137769 W [0362] • DE 102005030051 A1 [0638] [0650] [0670] Nepatentna literatura koja je navedena u opisu: • ORTEGA et al. Biochimica et Biophysica Acta-Reviews on Cancer, 2002, vol. 1602 (1), 73-87 [0002] [0003] [0004] • SHAPIRO. Journal of Clinical Oncology, 2006, vol. 24 (11), 1770-1783 [0002] [0003] • LUNDBERG et al. Molecular and Cellular Biology, 1998, vol. 18 (2), 753-761 [0002] • KAMB et al. Science, 1994, vol. 264 (5157), 436-440 [0002] [0004] • SHERR et al. Genes & Development, vol. 13 (12), 1501-1512 [0002] • AMIN et al. Archives of Pathology & Laboratory Medicine, 2003, vol. 127 (4), 424-431 [0003] • OUDAT et al. Modern Pathology, 2001, vol. 14 (1), 175A [0003] • BERGSAGEL et al. Immunological Reviews, 2003, vol. 194 (1), 96-104 [0003] • JIANG et al. Cancer Research, 1992, vol. 52 (10), 2980-2983 [0004] • AMOLD et al. Journal of Clinical Oncology, 2005 [0004] • SIRVENT et al. American Journal of Surgical Pathology, 2007, vol. 31 (10), 1476-1489 [0004] • BRAMBILLA et al. Journal of Pathology, 1999, vol. 188 (4), 351-360 [0004] • COWGILL et al. American Journal of Surgery, 2003, vol. 186 (3), 279-286 [0004] • GAZZERI et al. Oncogene, 1998, vol. 16 (4), 497-504 [0004] • DAILEY et al. Cytokine & Growth Factor Reviews, 2005, vol. 16 (2), 233-247 [0005] • ENGELMAN. Nature Reviews Cancer, 2009, vol. 9 (8), 550-562 [0005] • GARCIA-ECHEVERRIA. Purinergic Signalling, 2009, vol. 5 (1), 117-125 [0005] • GRAY-SCHOPFER et al. Cancer and Metastesis Reviews, 2005, vol. 24 (1), 165-183 [0005] • JOHN et al. Oncogene, 2009, vol. 28, S14-S23 [0005] • SHARMA et al. Nature Reviews Cancer, 2007, vol. 7 (3), 169-181 [0005] • MORIARTY K.J. et al. Bioorg Med Chem Lett, 2006, vol. 16, 5778-5783 [0006] • Remington’s Pharmaceutical Sciences. Mack Publishing Company, 1985 [0053] • STAHL; WERMUTH. Handbook of Pharmaceutical Salts: Properties, Selection, and Use. Wiley-VCH, 2002 [0053] • GREEN ; WUTTS. Protective Groups in Organic Synthesis [0114] • AMIN, H. M. ; MCDONNELL, T. J. ; MEDEIROS, L. J. ; RASSIDAKIS, G. Z. ; LEVENTAKI, V.; ; O’CONNOR, S. L. ; KEATING, M. J. ; LAI, R. Characterization of 4 mantle cell lymphoma cell lines – Establishment of an in vitro study model. Arch. Pathol. Lab. Med., 2003, vol. 127, 424-431 [0886]
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