HRP20140270T1 - Supstituirane 3-fenilpropionske kiseline i njihova uporaba - Google Patents

Supstituirane 3-fenilpropionske kiseline i njihova uporaba Download PDF

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HRP20140270T1
HRP20140270T1 HRP20140270AT HRP20140270T HRP20140270T1 HR P20140270 T1 HRP20140270 T1 HR P20140270T1 HR P20140270A T HRP20140270A T HR P20140270AT HR P20140270 T HRP20140270 T HR P20140270T HR P20140270 T1 HRP20140270 T1 HR P20140270T1
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Croatia
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methyl
represents hydrogen
fluorine
formula
trifluoromethyl
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HRP20140270AT
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Thomas Lampe
Michael Hahn
Johannes-Peter Stasch
Karl-Heinz Schlemmer
Frank Wunder
Sherif El Sheikh
Volkhart Min-Jian Li
Eva-Maria Becker
Friederike Stoll
Andreas Knorr
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Bayer Intellectual Property Gmbh
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Claims (10)

1. Spoj sa formulom (I) [image] naznačen time da R1A predstavlja vodik, fluor, metil, trifluorometil, etil, 1,1-difluoroetil, 2,2,2-trifluoroetil, n-propil, ciklopropil ili ciklobutil, R1B predstavlja vodik ili metil, R2A predstavlja vodik, metil, trifluorometil, etil, 1,1-difluoroetil, 2,2,2-trifluoroetil ili n-propil, R2B predstavlja vodik ili metil, ili R1A i R2A su vezani jedan na drugi i zajedno s atomima ugljika na koje su vezani tvore ciklopropilni prsten sa formulom [image] gdje R1B i R2B imaju gore navedena značenja, ili R2A i R2B su vezani jedan na drugi i zajedno s atomom ugljika na koji su vezani tvore cikličku skupinu sa formulom [image] gdje n predstavlja broj 1, 2 ili 3, R3 predstavlja vodik, fluor, metil ili trifluorometil, R4 predstavlja vodik, fluor, klor, cijano, metil, trifluorometil ili etil, R5A predstavlja metil, trifluorometil ili etil, R5B predstavlja trifluorometil, ili R5A i R5B su vezani jedan na drugi i zajedno s atomom ugljika na koji su vezani tvore difluoro-supstituirani cikloalkilni prsten sa formulom [image] R6 predstavlja vodik, fluor, klor, brom, cijano, (C1-C4)-alkil, (C2-C4)-alkenil, ciklopropil ili ciklobutil, gdje (C1-C4)-alkil i (C2-C4)-alkenil mogu biti supstituirani do tri puta sa fluorom i ciklopropil i ciklobutil mogu biti supstituirani do dva puta fluorom, te R7 predstavlja vodik, fluor, klor, cijano, metil, trifluorometil, etil, metoksi ili trifluorometoksi, ili njihove soli, solvati ili solvati njihovih soli.
2. Spoj sa formulom (I) prema zahtjevu 1 naznačen time da R1A predstavlja vodik, metil, trifluorometil, etil, n-propil, ciklopropil ili ciklobutil, R1B predstavlja vodik ili metil, R2A predstavlja vodik, metil, trifluorometil, etil ili n-propil, R2B predstavlja vodik ili metil, ili R2A i R2B su vezani jedan na drugi i zajedno s atomom ugljika na koji su vezani tvore cikličku skupinu sa formulom [image] u kojoj n predstavlja broj 1 ili 2, R3 predstavlja vodik, fluor ili metil, R4 predstavlja vodik, fluor, klor, cijano, metil ili trifluorometil, R5A predstavlja metil ili etil, R5B predstavlja trifluorometil, ili R5A i R5B su vezani jedan na drugi i zajedno s atomom ugljika na koji su vezani tvore difluoro-supstituirani cikloalkilni prsten sa formulom [image] R6 predstavlja fluor, klor, (C1-C4)-alkil, (C2-C3)-alkenil, ciklopropil ili ciklobutil, gdje (C1-C4)-alkil i (C2-C3)-alkenil mogu biti supstituirani do tri puta sa fluorom, i ciklopropil i ciklobutil mogu biti supstituirani do dva puta fluorom, te R7 predstavlja vodik, fluor, klor, metil ili metoksi, ili njihove soli, solvati ili solvati njihovih soli.
3. Spoj sa formulom (I) prema zahtjevu 1 ili 2 naznačen time da R1A predstavlja vodik, metil ili etil, R1B predstavlja vodik, R2A predstavlja vodik, metil, trifluorometil, etil ili n-propil, R2B predstavlja vodik ili metil, ili R2A i R2B su vezani jedan na drugi i zajedno s atomom ugljika na koji su vezani tvore cikličku skupinu sa formulom [image] gdje n predstavlja broj 1 ili 2, R3 predstavlja vodik, R4 predstavlja fluor, klor ili metil, R5A predstavlja metil, R5B predstavlja trifluorometil, ili R5A i R5B su vezani jedan na drugi i zajedno s atomom ugljika na koji su vezani tvore difluoro-supstituirani ciklopentilni prsten sa formulom [image] R6 predstavlja fluor, klor, metil, trifluorometil, etil, 1,1-difluoroetil, 2,2,2-trifluoroetil, izopropil, tert-butil, 1,1,1-trifluoro-2-metilpropan-2-il, vinil, 1-fluorovinil, ciklopropil, 2,2-difluorociklopropil, ciklobutil ili 3,3-difluorociklobutil, i R7 predstavlja vodik, fluor, klor ili metil, ili njihove soli, solvati ili solvati njihovih soli.
4. Postupak za dobivanje spoja sa formulom (I) kako je definirano u bilo kojem zahtjevu od 1 do 3, naznačen time da karboksilna kiselina da formulom (II) [image] gdje R5A, R5B, R6 i R7 imaju značenja dodijeljena u bilo kojem zahtjevu od 1 do 3, su spojeni u inertnom otapalu uz pomoć sredstva za kondenzaciju ili preko intermedijera odgovarajućeg karbonil klorida u prisutnosti baze sa aminom prema formuli (III) [image] gdje R1A, R1B, R2A, R2B, R3 i R4 imaju značenja dodijeljena u bilo kojem zahtjevu od 1 do 3, te T1 predstavlja (C1-C4)-alkil ili benzil, da se dobije karboksamid sa formulom (IV) [image] gdje R1A, R1B, R2A, R2B, R3, R4, R5A, R5B, R6, R7 i T1 imaju gore navedena značenja, radikal estera T1 se tada uklanja sa baznom ili kiselom solvolizom ili, ako T1 predstavlja benzil, također sa hidrolizom, što daje karboksilnu kiselinu sa formulom (I), te se spojevi sa formulom (I) razdvajaju gdje je prikladno, postupcima koji su poznati stručnjaku u ovom području tehnike u njihove enantiomere i/ili diastereomere, i/ili gdje je prikladno reagiraju sa prikladnim (i) otapalima i/ili (ii) bazama da se dobiju solvati, soli i/ili solvati njihovih soli.
5. Spoj kako je definirano u bilo kojem zahtjevu od 1 do 3 naznačen time da je za liječenje i/ili sprečavanje bolesti.
6. Spoj kako je definirano u bilo kojem zahtjevu od 1 do 3 naznačen time da je za uporabu u postupku liječenja i/ili sprečavanja srčanog zastoja, angine pektoris, hipertenzije, plućne hipertenzije, ishemija, vaskularnih poremećaja, oslabljene mikrocirkulacije, tromboembolijskih poremećaja i arterioskleroze.
7. Uporaba spoja kako je definirano u bilo kojem zahtjevu od 1 do 3 naznačena time da je za pripravu medikamenta za liječenje i/ili sprečavanje srčanog zastoja, angine pektoris, hipertenzije, plućne hipertenzije, ishemija, vaskularnih poremećaja, oslabljene mikrocirkulacije, tromboembolijskih poremećaja i arterioskleroze.
8. Medikament naznačen time da sadrži spoj kako je definirano u bilo kojem zahtjevu od 1 do 3 u kombinaciji sa jednom ili više inertnih, ne-toksičnih, farmaceutski pogodnih pomoćnih tvari.
9. Medikament naznačen time da sadrži spoj kako je definirano u bilo kojem zahtjevu od 1 do 3 u kombinaciji sa jednim ili više dodatnih aktivnih spojeva odabranih iz skupine koja sadrži organske nitrate, NO donore, inhibitore cGMP-PDE, stimulatore guanilat ciklaze, sredstava koja imaju antitrombotičku aktivnost, sredstava koja snižavaju krvni tlak, te sredstava koja mijenjaju metabolizam lipida.
10. Medikament prema zahtjevu 8 ili 9 naznačen time da je za liječenje i/ili sprečavanje srčanog zastoja, angine pektoris, hipertenzije, plućne hipertenzije, ishemija, vaskularnih poremećaja, oslabljene mikrocirkulacije, tromboembolijskih poremećaja i arterioskleroze.
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