HRP20161702T1 - Novi derivati pirazina - Google Patents

Novi derivati pirazina Download PDF

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HRP20161702T1
HRP20161702T1 HRP20161702TT HRP20161702T HRP20161702T1 HR P20161702 T1 HRP20161702 T1 HR P20161702T1 HR P20161702T T HRP20161702T T HR P20161702TT HR P20161702 T HRP20161702 T HR P20161702T HR P20161702 T1 HRP20161702 T1 HR P20161702T1
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Croatia
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pyrazine
cyclopropylmethoxy
amide
carboxylic acid
cyclopropyl
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HRP20161702TT
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Caterina Bissantz
Baledi DHURWASULU
Uwe Grether
Anindya HAZRA
Paul Hebeisen
Stephan Roever
Mark Rogers-Evans
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F. Hoffmann - La Roche Ag
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Publication of HRP20161702T1 publication Critical patent/HRP20161702T1/hr

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Claims (17)

1. Spoj, naznačen time, da ima sljedeću formulu (I): [image] u kojoj R1je halofenil ili cikloalkilalkoksi; R2 je cikloalkil, azetidinil ili difluoroazetidinil; jedan od R3 i R4 je vodik, a drugi je -(CR5R6)-R7 ili -A-R7; ili R2 je cikloalkil te R3 i R4 zajedno s atomom dušika na kojega su priključeni, tvore piperidinil ili piperidinilamin; R5 i R6 su neovisno odabrani od sljedećih: vodik, alkil, haloalkil, cikloalkil, cikloalkilalkil, fenil, fenilalkil i halofenil; ili R5 i R6 zajedno s atomom ugljika na kojega su priključeni, tvore cikloalkil ili oksetanil; R7 je cijano, karboksi, 5-metil-[1,2,4]oksadiazol-3-il, 5-amino-[1,2,4]oksadiazol-3-il, 5-alkoksi-[1,2,4]oksadiazol-3-il, tiazolil, alkiltiazolil, piridinil, alkilaminokarbonil, hidroksialkil, alkoksialkil, aminokarbonil, alkoksikarbonil, dialkilaminokarbonil, metansulfonil-alkil, 2-[1,2,4]oksadiazol-5-il)-alkil, 2-metil-2H-[1,2,4]triazol-3-il, 2-(2-metil-2H-[1,2,4]triazol-3-il)-alkil, 2,4-dihidro-[1,2,4]triazol-3-on-5-il, 2-(2,4-dihidro-[1,2,4]triazol-3-on-5-il)-alkil, fenil, fenilalkil, piridinilalkil, pirazolil, pirazolilalkil, [1,2,4]triazol-1-il, 2-([1,2,4]triazol-1-il)-alkil, alkilaminokarbonilalkil, hidroksialkilaminokarbonil, hidroksialkilaminokarbonilalkil, haloalkilaminokarbonil, 5-fenil-2-metil-oksazol-4-il-alkil, aminokarbonilalkil ili halogen; i A je cikloheksil ili tiofenil; pod uvjetom da, kada R2 je azetidinil ili difluoroazetidinil i R7 je hidroksialkil, haloalkil, tiazolil, piridinil, 2-([1,2,4]oksadiazol-5-il)-alkil, piridinilalkil, pirazolilalkil, 2-([1,2,4]triazol-1-il)-alkil, aminokarbonil ili alkoksikarbonil, tada jedan od R5 i R6 je cikloalkil, cikloalkilalkil, fenil, halofenil ili fenilalkil, a drugi je vodik ili alkil; ili tada R5 i R6 zajedno s atomom ugljika na kojega su priključeni, tvore cikloalkil ili oksetanil; ili njegova farmaceutski prihvatljiva sol ili njegov ester.
2. Spoj prema zahtjevu 1, naznačen time, da R1 je cikloalkilalkoksi.
3. Spoj prema zahtjevu 1 ili 2, naznačen time, da R1 je ciklopropilmetoksi.
4. Spoj prema bilo kojem od zahtjeva 1 do 3, naznačen time, da R2 je cikloalkil ili difluoroazetidinil.
5. Spoj prema bilo kojem od zahtjeva 1 do 4, naznačen time, da R2 je ciklopropil ili difluoroazetidinil.
6. Spoj prema bilo kojem od zahtjeva 1 do 5, naznačen time, da su R5 i R6neovisno odabrani od sljedećih: vodik, alkil, cikloalkil i cikloalkilalkil.
7. Spoj prema bilo kojem od zahtjeva 1 do 6, naznačen time, da su R5 i R6neovisno odabrani od sljedećih: vodik, etil, tert-butil, izo-butil, ciklopropil, ciklopropilmetil i ciklobutilmetil.
8. Spoj prema bilo kojem od zahtjeva 1 do 7, naznačen time, da je jedan od R5 i R6odabran od sljedećih: etil, tert-butil, izo-butil, ciklopropilmetil i ciklobutilmetil, a drugi je vodik ili etil.
9. Spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time, da R7je cijano, karboksi, 5-metil-[1,2,4]oksadiazol-3-il, 5-amino-[1,2,4]oksadiazol-3-il, tiazolil, alkiltiazolil, piridinil, alkilaminokarbonil, hidroksialkil, alkoksialkil, aminokarbonil, dialkilaminokarbonil, alkoksikarbonil, 5-metil-tiazol-2-il, aminokarbonilalkil ili fenilalkil.
10. Spoj prema bilo kojem od zahtjeva 1 do 9, naznačen time, da R7je alkoksialkil, aminokarbonil, dialkilaminokarbonil, alkoksikarbonil, 5-metil-tiazol-2-il, aminokarbonilalkil, 5-metil-[1,2,4]oksadiazol-3-il, hidroksialkil ili fenilalkil.
11. Spoj prema bilo kojem od zahtjeva 1 do 10, naznačen time, da R7je metoksikarbonil, aminokarbonil, dimetilaminokarbonil, 5-metil-tiazol-2-il, 5-metil-[1,2,4]oksadiazol-3-il, aminokarbonilmetil, hidroksimetil, metoksietil ili feniletil.
12. Spoj prema bilo kojem od zahtjeva 1 do 11, naznačen time, da je odabran od sljedećih: 6-(3-kloro-fenil)-5-ciklopropil-pirazino-2-karboksilna kiselina-[1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 6-(3-kloro-fenil)-5-ciklopropil-pirazino-2-karboksilna kiselina-(cijano-dimetil-metil)-amid; 6-( 3-kloro-fenil)-5-ciklopropil-pirazino-2-karboksilna kiselina-[1-(5-metil-[1,2,4]oksadiazol-3-il)-ciklobutil]-amid; 6-(3-kloro-fenil)-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 5-azetidin-1-il-6-(3-kloro-fenil)-pirazin-2-karboksilna kiselina-[1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 6-(3-kloro-fenil)-5-ciklopropil-pirazin-2-karboksilna kiselina-(1-metil-1-tiazol-2-il-etil)-amid; 6-(3-kloro-fenil)-5-ciklopropil-pirazin-2-karboksilna kiselina-piperidin-1-ilamid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-2,2-dimetil-1-metilkarbamoil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-(5-metil-[1,2,4]oksadiazol-3-il)-ciklobutil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(3-hidroksi-1,1-dimetil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-hidroksimetil-ciklobutil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[1-(5-metil-[1,2,4]oksadiazol-3-il)-ciklobutil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-hidroksimetil-1-metil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-2,2-dimetil-1-metilkarbamoil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-karbamoilfenil-metil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-1-ciklopropilmetil-2-hidroksi-2-metil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-ciklopropilmetil-2-hidroksi-2-metilpropil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-piperidin-1-ilamid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-hidroksimetil-2,2-dimetil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[(S)-2-ciklopropil-1-(5-metil-(1,2,4]oksadiazol-3-il)-etil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-ciklopropil-2-hidroksi-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-karbamoil-fenil-metil)-amid; (S)-2-((5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karbonil)-amino]-3,3-dimetil-butirna kiselina-metilester; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-2-ciklopropil-1-metilkarbamoil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-2-ciklopropil-1-dimetilkarbamoil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-3-metil-1-metilkarbamoil-butil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-dimetilkarbamoil-3-metil-butil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-2-ciklopropil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-3-metil-butil)-amid; 2-[(5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karbonil)-amino]-2-etil-butirna kiselina-metilester; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-2-ciklopropil-1-metilkarbamoil-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-2-ciklopropil-1-dimetilkarbamoil-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina- ((S)-3-metil-1-metilkarbamoil-butil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-1-dimetilkarbamoil-3-metil-butil)-amid; (S)-3-ciklopropil-2-[(5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karbonil)-amino]-propionska kiselina-metilester; (S)-3-ciklopropil-2-{[6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karbonil]-amino}-propionska kiselina-metilester; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-2-fenil-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-2-fenil-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-2-ciklopropil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[(S)-ciklopropil-(5-metil-[1,2,4]oksadiazol-3-il)-metil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[(R)-ciklopropil-(5-metil-[1,2,4]oksadiazol-3-il)-metil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[(S)-ciklopropil-(5-metil-[1,2,4]oksadiazol-3-il)-metil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[(R)-ciklopropil-(5-metil-[1,2,4]oksadiazol-3-il)-metil]-amid; (S)-2-[(5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karbonil)-amino]-3,3-dimetil-butirna kiselina; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-piridin-2-il-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((R)-2,2,2-trifluoro-1-piridin-2-il-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-2,2,2-trifluoro-1-piridin-2-il-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-2,2,2-trifluoro-1-piridin-2-il-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-etil-1-metilkarbamoilpropil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((R)-1-hidroksimetil-1,2-dimetil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-hidroksimetil-1,2-dimetil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-etil-1-metilkarbamoil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[1-metil-1-(4-metil-tiazol-2-il)-etil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-metil-1-(4-metil-tiazol-2-il)-etil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[(R)-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[1-(5-amino-[1,2,4]oksadiazol-3-il)-1-metiletil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-(5-amino-[1,2,4]oksadiazol-3-il)-1-metil-etil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-1-feniletil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[2-ciklopropil-1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-ciklopropil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[1-ciklopropil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[(S)-karbamoil-(4-fluoro-fenil)-metil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[(S)-karbamoil-(4-fluoro-fenil)-metil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[(S)-2-ciklopropil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; (S)-2-{[6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karbonil]-amino}-4-metil-pentanska kiselina-metilester; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[(S)-3-metil-1-(2,2,2-trifluoroetilkarbamoil)-butil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[(S)-karbamoil-(4-kloro-fenil)-metil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(4-hidroksi-1,1-dimetil-butil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1,1-dimetil-3-piridin-4-il-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[1,1-dimetil-2-(5-metil-2-fenil-oksazol-4-il)-etil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1,1-dimetil-3-piridin-4-il-butil)-amid; 1-{[6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karbonil]-amino}-ciklobutan-karboksilna kiselina-metilester; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-[1-metil-1-(5-metil-tiazol-2-il)-etil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-metil-1-(5-metil-tiazol-2-il)-etil]-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-karbamoilmetil-2-metil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-((S)-1-karbamoilmetil-2-metil-propil)-amid; (+)-6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[2-ciklopropil-1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; (-)-6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[2-ciklopropil-1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 2-ciklopropil-2-{[6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karbonil]-amino}-propionska kiselina-metilester; (+)-6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1R,2S)-rel-2-karbamoil-cikloheksil)-amid; (-)-5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-cis-2-karbamoil-cikloheksil)-amid; (+)-5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-cis-2-karbamoil-cikloheksil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(3-karbamoilmetil-oksetan-3-il)-amid; 6-ciklopropilmetoksi-5-(3, 3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(3-karbamoilmetil-oksetan-3-il)-amid; (+)-6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-ciklopropil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; (-)-6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-ciklopropil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-karbamoil-2-metil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-karbamoil-cikloheksil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-hidroksimetil-cikloheksil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-dimetilkarbamoil-2-metil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-dimetilkarbamoil-2-metil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(5-klorotiofen-2-il)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-hidroksimetil-cikloheksil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(3-metoksi-1,1-dimetil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(2-ciklobutil-1-metilkarbamoil-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(2-ciklobutil-1-dimetilkarbamoil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(2-ciklobutil-1-metil-karbamoil-etil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(3-metoksi-1,1-dimetil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-ciklobutilmetil-2-hidroksietil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-karbamoil-2-ciklobutiletil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1,1-dimetil-3-fenil-propil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(2-ciklobutil-1-dimetilkarbamoil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-karbamoil-2-ciklobutil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(1-ciklobutilmetil-2-hidroksi-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-(2-karbamoil-1,1-dimetil-etil)-amid; i 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(2-karbamoil-1,1-dimetiletil)-amid.
13. Spoj prema bilo kojem od zahtjeva 1 do 12, naznačen time, da je odabran od sljedećih: (S)-2-[(5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karbonil)-amino]-3,3-dimetil-butirna kiselina-metilester; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-dimetilkarbamoil-3-metil-butil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-2-ciklopropil-etil)-amid; 5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karboksilna kiselina-((S)-1-karbamoil-3-metil-butil)-amid; 2-[(5-ciklopropil-6-ciklopropilmetoksi-pirazin-2-karbonil)-amino]-2-etil-butirna kiselina-metilester; (S)-3-ciklopropil-2-{[6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karbonil]-amino}-propionska kiselina-metilester; (S)-2-{[6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karbonil]-amino}-4-metil-pentanska kiselina-metilester; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[1-metil-1-(5-metil-tiazol-2-il)-etil]-amid; (-)-6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-[2-ciklopropil-1-metil-1-(5-metil-[1,2,4]oksadiazol-3-il)-etil]-amid; 2-ciklopropil-2-{[6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karbonil]-amino}-propionska kiselina-metilester; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(3-karbamoilmetil-oksetan-3-il)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-hidroksimetil-cikloheksil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(3-metoksi-1,1-dimetil-propil)-amid; 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1-ciklobutilmetil-2-hidroksietil)-amid; i 6-ciklopropilmetoksi-5-(3,3-difluoro-azetidin-1-il)-pirazin-2-karboksilna kiselina-(1,1-dimetil-3-fenil-propil)-amid.
14. Postupak proizvodnje spoja prema bilo kojem od zahtjeva 1 do 13, naznačen time, da obuhvaća reakciju spoja sljedeće formule (A): [image] sa spojem formule NHR3R4, s veznim sredstvom za tvorbu amidne veze i s lužinom, pri čemu su R1 do R4 definirani prema bilo kojem od zahtjeva 1 do 11.
15. Spoj prema bilo kojem od zahtjeva 1 do 13, naznačen time, da se upotrebljava kao terapeutski djelotvorna tvar.
16. Farmaceutski sastav, naznačen time, da obuhvaća spoj prema bilo kojem od zahtjeva 1 do 13, i terapeutski inertan nosač.
17. Spoj prema bilo kojem od zahtjeva 1 do 13, naznačen time, da se upotrebljava u liječenju ili profilaksi bolova, ateroskleroze, regulacije koštane mase, upale, ishemije, reperfuzijske ozljede, sustavne fibroze, fibroze jetre, fibroze pluća, fibroze bubrega, kronične alogenske nefropatije, kongestivnog srčanog zastoja, infarkta miokarda, sustavne skleroze, glomerulonefropatije, termalne ozljede, opekotine, hipertrofije ožiljaka, keloida, gingivitis pireksije, ciroze jetre ili tumora.
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IN2015DN03145A (hr) * 2012-12-07 2015-10-02 Hoffmann La Roche
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AR099932A1 (es) * 2014-04-04 2016-08-31 Hoffmann La Roche Derivados de piridina
WO2017000125A1 (en) 2015-06-29 2017-01-05 Merck Sharp & Dohme Corp. Purine inhibitors of human phosphatidylinositol 3-kinase delta
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EP3642200B1 (en) 2017-06-20 2023-05-03 F. Hoffmann-La Roche AG Pyridine derivatives
CN112638430B (zh) * 2018-06-27 2023-05-16 豪夫迈·罗氏有限公司 放射性标记的大麻素受体2配体
PE20210368A1 (es) * 2018-06-27 2021-02-26 Eth Zuerich Nuevos compuestos de piridina y pirazina como inhibidores del receptor cannabinoide 2
WO2020002270A1 (en) * 2018-06-27 2020-01-02 F. Hoffmann-La Roche Ag Pyridine and pyrazine derivatives as preferential cannabinoid 2 agonists
WO2023106973A1 (ru) * 2021-12-10 2023-06-15 Общество С Ограниченной Ответственностью "Валента-Интеллект" Новые гепатопротекторные средства

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US7326706B2 (en) * 2003-08-15 2008-02-05 Bristol-Myers Squibb Company Pyrazine modulators of cannabinoid receptors
US20060199828A1 (en) 2005-03-04 2006-09-07 Georg Jaeschke Pyrazine-2-carboxyamide derivatives
RU2404164C2 (ru) * 2005-04-06 2010-11-20 Ф.Хоффманн-Ля Рош Аг Производные пиридин-3-карбоксамида в качестве обратных агонистов св1
US7629346B2 (en) * 2006-06-19 2009-12-08 Hoffmann-La Roche Inc. Pyrazinecarboxamide derivatives as CB1 antagonists
MX2009003222A (es) * 2006-10-04 2009-04-06 Hoffmann La Roche Derivados de 3-piridinocarboxamida y 2-pirazinocarboxamida como agentes elevadores de colesterol de lipoproteina de alta densidad.
EP2076499B1 (en) * 2006-10-04 2010-05-12 F.Hoffmann-La Roche Ag Pyrazine-2-carboxamide derivatives as cb2 receptor modulators
US8088920B2 (en) * 2008-03-31 2012-01-03 Hoffmann-La Roche Inc. 3-trifluoromethyl-pyrazine-2-carboxylic acid amide derivatives as HDL-cholesterol raising agents

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CA2851930A1 (en) 2013-05-02
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