HRP20170638T1 - MODULATORI RETINOIDNIMA SRODNOG SIROČETA RECEPTORA γ (ROR-γ), NAMIJENJENI UPOTREBI U LIJEČENJU AUTOIMUNIH I PROTUUPALNIH BOLESTI - Google Patents

MODULATORI RETINOIDNIMA SRODNOG SIROČETA RECEPTORA γ (ROR-γ), NAMIJENJENI UPOTREBI U LIJEČENJU AUTOIMUNIH I PROTUUPALNIH BOLESTI Download PDF

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HRP20170638T1
HRP20170638T1 HRP20170638TT HRP20170638T HRP20170638T1 HR P20170638 T1 HRP20170638 T1 HR P20170638T1 HR P20170638T T HRP20170638T T HR P20170638TT HR P20170638 T HRP20170638 T HR P20170638T HR P20170638 T1 HRP20170638 T1 HR P20170638T1
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methyl
compound
substituted
phenyl
chloro
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Fangbin HAN
Hui Lei
Xichen Lin
Qinghua Meng
Yonghui Wang
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Glaxo Group Limited
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    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
    • C07D211/16—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms with acylated ring nitrogen atom
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
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    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
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    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
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    • 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
    • C07D471/04—Ortho-condensed systems

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Claims (21)

1. Spoj Formule I ili njegova farmaceutski prihvatljiva sol [image] naznačen time što: R1 je: – C1-C6 alkil; – metil, supstituiran s i) C3-C5 cikloalkilom; ii) fenoksi; ili iii) fenilom i drugim supstituentom, kojeg se bira iz skupine koju čine: metil, halogen i metoksi; – etil, supstituiran s i) fenilom, gdje navedeni fenil može biti supstituiran s halogenom ili metoksi, ili ii) heteroarilom; – benzil, gdje fenilna skupina u navedenom benzilu može biti supstituirana s halogenom, metoksi ili SO2CH2CH3; – C2 alkenil, koji može biti supstituiran s jednim F i jednim fenilom; – C3-C7 cikloalkil, gdje navedeni cikloalkil može biti supstituiran s jednim ili dva supstituenta, koje se bira iz skupine koju čine fenil, metil i F; ili navedeni cikloalkil može biti kondenziran s fenilnim prstenom; – heterocikloalkil, koji može biti supstituiran s jednim ili dva C1-C3 alkil; – heteroaril, koji može biti supstituiran s jednim do dva supstituenta, koje se bira iz skupine koju čine: C1-C3 alkil, C1-C3 alkoksi i CF3; i – fenil, supstituiran s jednim do tri supstituenta, koje se bira iz skupine koju čine: i) halogen; ii) CN; iii) C1-C3 alkil, koji može biti supstituiran s jednim do tri F; iv) C1-C3 alkoksi; v) (CH2)nNRaRb; vi) C(O)CH3; i vii) CH2OCH3; R2 je halogen ili C1-C3 alkil; R3 je halogen ili metil; R4 je H ili metil; R5 je C1-C3 alkil; R6 je C1-C3 alkil; R7 se bira iz skupine koju čine: – C1-C7 alkil, koji može biti supstituiran s jednim ili više supstituenata, koje se bira iz skupine koju čine halogen, C3-C5 cikloalkil i CF3; – C3-C7 cikloalkil, koji može biti supstituiran s jednim ili dva supstituenta, koje se bira iz skupine koju čine F, CH2F, CHF2, metil i metoksi, svaki k je 0 ili 1; svaki p je 0 ili 1; svaki n je 0, 1 ili 2; svaki Ra je H ili C1-C3 alkil; svaki Rb je H ili C1-C3 alkil.
2. Spoj ili sol u skladu s patentnim zahtjevom 1, naznačen time što je R1 heteroaril, supstituiran s C1-C3 alkilom.
3. Spoj ili sol u skladu s patentnim zahtjevom 1 ili patentnim zahtjevom 2, naznačen time što je R1 piridinil, supstituiran s metilom.
4. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 3, naznačen time što je R2 metil.
5. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 4, naznačen time što je k 1, a R3 je Cl ili F.
6. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 5, naznačen time što je R4 H.
7. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time što je R5 metil.
8. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time što je p 0.
9. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 8, naznačen time što je R7 C3-C6 cikloalkil, koji može biti supstituiran s jednim ili dva F ili metil.
10. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačen time što je R7 ciklobutil, supstituiran s metil ili dva F.
11. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačen time što je R7 ciklopentil.
12. Spoj ili sol u skladu s patentnim zahtjevom 1, naznačen time što se spoj bira između: (S)-N-(3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-5-fluor-2-metilfenil)-2-metilpirimidin-5-karboksamida; (S)-N-(5-klor-3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-2-metilfenil)-6-metilnikotinamida; (S)-3-cijano-N-(3-((4-(3,3-difluorciklobutankarbonil)-3-metilpiperazin-1-il)metil)-5-fluor-2-metilfenil)benzamida; (S)-N-(5-klor-3-((4-(2-ciklopropilacetil)-3-metilpiperazin-1-il)metil)-2-metilfenil)-6-metilnikotinamida; N-(5-fluor-2-metil-3-(((S)-3-metil-4-((cis)-3-metilciklobutankarbonil)piperazin-1-il)metil)fenil)-6-metilnikotinamida; N-(5-fluor-2-metil-3-(((S)-3-metil-4-((trans)-3-metilciklobutankarbonil)piperazin-1-il)metil)fenil)-6-metilnikotinamida; N-(5-klor-2-metil-3-(((S)-3-metil-4-((trans)-3-metilciklobutankarbonil)piperazin-1-il)metil)fenil)-6-metilnikotinamida; N-(5-klor-2-metil-3-(((S)-3-metil-4-((cis)-3-metilciklobutankarbonil)piperazin-1-il)metil)fenil)-6-metilnikotinamida; N-(5-klor-2-metil-3-(((S)-3-metil-4-((cis)-3-metilciklobutankarbonil)piperazin-1-il)metil)fenil)-2-metilpirimidin-5-karboksamida; N-(5-klor-2-metil-3-(((S)-3-metil-4-((trans)-3-metilciklobutankarbonil)piperazin-1-il)metil)fenil)-2-metilpirimidin-5-karboksamida; i (S)-N-(5-klor-3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-2-metilfenil)-2-metilpirimidin-5-karboksamida.
13. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je (S)-3-cijano-N-(3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-5-fluor-2-metilfenil)benzamid; ili njegova farmaceutski prihvatljiva sol.
14. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je (S)-N-(5-klor-3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-2-metilfenil)-6-metilnikotinamid; ili njegova farmaceutski prihvatljiva sol.
15. Spoj naznačen time što je (S)-N-(5-klor-3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-2-metilfenil)-6-metilnikotinamid, Formule: [image] .
16. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je N-(5-klor-2-metil-3-(((S)-3-metil-4-((cis)-3-metilciklobutankarbonil)piperazin-1-il)metil)fenil)-6-metilnikotinamid; ili njegova farmaceutski prihvatljiva sol.
17. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 16, ili njegova farmaceutski prihvatljiva sol, naznačen time što je namijenjen upotrebi u terapiji.
18. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 16, ili njegova farmaceutski prihvatljiva sol, naznačen time što je namijenjen upotrebi u liječenju psorijaze.
19. (S)-N-(5-Klor-3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-2-metilfenil)-6-metilnikotinamid, naznačen time što je namijenjen upotrebi u liječenju psorijaze.
20. Farmaceutski pripravak, naznačen time što sadrži spoj Formule I u skladu s bilo kojim od patentnih zahtjeva 1 do 16, ili njegovu farmaceutski prihvatljivu sol, kao i farmaceutski prihvatljivu podlogu ili pomoćnu tvar.
21. Farmaceutski pripravak, naznačen time što sadrži (S)-N-(5-klor-3-((4-(ciklopentankarbonil)-3-metilpiperazin-1-il)metil)-2-metilfenil)-6-metilnikotinamid, kao i farmaceutski prihvatljivu podlogu ili pomoćnu tvar.
HRP20170638TT 2012-12-06 2017-04-24 MODULATORI RETINOIDNIMA SRODNOG SIROČETA RECEPTORA γ (ROR-γ), NAMIJENJENI UPOTREBI U LIJEČENJU AUTOIMUNIH I PROTUUPALNIH BOLESTI HRP20170638T1 (hr)

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CN2012001636 2012-12-06
CN2013000182 2013-02-25
CN2013000803 2013-07-01
EP13799318.4A EP2928885B1 (en) 2012-12-06 2013-12-05 Modulators of the retinoid-related orphan receptor gamma (ror-gamma) for use in the treatment of autoimmune and inflammatory diseases
PCT/EP2013/075594 WO2014086894A1 (en) 2012-12-06 2013-12-05 Modulators of the retinoid-related orphan receptor gamma (ror-gamma) for use in the treatment of autoimmune and inflammatory diseases

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