HRP20171981T1 - Derivati pirazolkarboksamida kao taar modulatora za uporabu u liječenju nekoliko poremećaja poput depresije, dijabetesa i parkinsonove bolesti - Google Patents

Derivati pirazolkarboksamida kao taar modulatora za uporabu u liječenju nekoliko poremećaja poput depresije, dijabetesa i parkinsonove bolesti Download PDF

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HRP20171981T1
HRP20171981T1 HRP20171981TT HRP20171981T HRP20171981T1 HR P20171981 T1 HRP20171981 T1 HR P20171981T1 HR P20171981T T HRP20171981T T HR P20171981TT HR P20171981 T HRP20171981 T HR P20171981T HR P20171981 T1 HRP20171981 T1 HR P20171981T1
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phenyl
pyrazole
carboxamide
morpholin
alkyl
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Guido Galley
Roger Norcross
Philippe Pflieger
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F. Hoffmann - La Roche Ag
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Claims (19)

1. Spoj, naznačen time, da ima sljedeću formulu: [image] u kojoj R1 je fenil, po potrebi supstituiran halogenom, C1-7-alkil, C3-6-cikloalkil, C1-7-alkoksi, cijano, C1-7-alkil supstituiran halogenom, C1-7-alkil supstituiran hidroksi skupinom, C1-7-alkoksi supstituiran halogenom ili C1-7-alkoksi supstuiran hidroksi skupinom; ili je piridin-2, -3 ili -4-il-skupina, po potrebi supstituirana halogenom, C1-7-alkil, C3-6-cikloalkil, cijano, C1-7-alkil supstituiran halogenom, C1-7-alkil supstituiran hidroksilom, C1-7-alkoksi, C1-7-alkoksi supstituiran halogenom ili C1-7-alkoksi supstituiran hidroksilnom skupinom; ili je pirimidin-2, -4 ili -5-il-skupina, po potrebi supstituirana halogenom, C1-7-alkil, C3-6-cikloalkil, C1-7-alkil supstituiran hidroksi skupinom ili C1-7-alkil supstituiran halogenom; ili je pirazin-2-il-skupina, po potrebi supstituirana halogenom, C1-7-alkil, C3-6-cikloalkil, C1-7-alkil supstituiran halogenom, C1-7-alkil supstituiran hidroksi ili cijano skupinom; ili je 2,2-difluorobenzo[d][l,3]dioksol-5-il ili tiazolil po potrebi supstituiran s C1-7-alkilom koji je supstituiran halogenom; R2 je vodik ili C1-7-alkil; R3 je vodik, amino ili C1-7-alkil; Z je veza, -CH2- ili -O-; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol.
2. Spoj formule IA prema patentnom zahtjevu 1, naznačen time, da je to: [image] gdje R2 je vodik ili C1-7-alkil; R3 je vodik, amino ili C1-7-alkil; R4 je vodik, halogen, C1-7-alkil, C3-6-cikloalkil, C1-7-alkoksi, cijano, C1-7-alkil supstituiran halogenom, C1-7-alkil supstituiran hidroksilom, C1-7-alkoksi supstituiran halogenom ili C1-7-alkoksi supstituiran hidroksi skupinom; n je 1 ili 2; Z je veza, -CH2- ili -O-; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol.
3. Spoj prema bilo kojem od zahtjeva 1 ili 2, naznačen time, da su spojevi sljedeći: (S)-5-metil-N-(4-(morfolin-2-il)fenil)-1-fenil-1H-pirazol-4-karboksamid; (S)-5-amino-1-(4-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-metoksifenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(3-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-cijanofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (R)-1-(4-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(3-cijanofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-bromo-2-cijanofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-(difluorometoksi)fenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(3-(difluorometoksi)fenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-cijano-2-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-cijano-3-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(2-cijano-4-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-N-(4-(morfolin-2-il)fenil)-1-(4-(trifluorometoksi)fenil)-1H-pirazol-4-karboksamid; (R)-1-(4-(difluorometoksi)fenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-(difluorometoksi)fenil)-5-metil-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-(difluorometoksi)fenil)-3-metil-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(4-cijanofenil)-5-metil-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (R)-1-(4-cijano-2-fluorofenil)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (RS)-1-(4-difluorometoksi-fenil)-1H-pirazol-4-karboksilna kiselina- (4-pirolidin-3-il-fenil)-amid; ili (RS)-1-(4-difluorometoksi-fenil)-1H-pirazol-4-karboksilna kiselina- (4-piperidin-3-il-fenil)-amid.
4. Spoj formule IB prema patentnom zahtjevu 1, naznačen time, da je to: [image] gdje [image] je piridin-2, -3 ili -4-il-skupina; R2 je vodik ili C1-7-alkil; R3 je vodik, amino ili C1-7-alkil; R5 je vodik, halogen, C1-7-alkil, C3-6-cikloalkil, cijano, C1-7-alkil supstituiran halogenom, C1-7-alkil supstituiran hidroksi skupinom, C1-7-alkoksi, C1-7-alkoksi supstituiran halogenom ili C1-7-alkoksi supstituiran hidroksi skupinom; n je 1 ili 2; Z je veza, -CH2- ili -O-; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol.
5. Spoj prema bilo kojem od zahtjeva 1 do 4, naznačen time, da su spojevi sljedeći: (S)-1-(5-kloropiridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(5-cijanopiridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(5-bromopiridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(5-jodopiridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-N-(4-morfolin-2-il)fenil)-1-(5-(trifluorometil)-piridin-2-Il)-1H-pirazol-4-karboksamid; (S)-N-(4-morfolin-2-il)fenil)-1-(4-(trifluorometil)-piridin-2-Il)-1H-pirazol-4-karboksamid; (S)-1-(4-kloropiridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(2-bromopiridin-4-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(6-metoksipiridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(3-fluoro-5-(trifluorometil)piridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(2-kloropiridin-4-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(6-etoksipiridin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-N-(4-(morfolin-2-il)fenil)-1-(2-(trifluorometil)piridin-4-il)-1H-pirazol-4-karboksamid; ili (S)-N-(4-(morfolin-2-il)fenil)-1-(6-(trifluorometil)piridin-3-il)-1H-pirazol-4-karboksamid.
6. Spoj s formulama IC1, IC2 i IC3 u skladu s patentnim zahtjevom 1, naznačen time, da su to: [image] gdje R2 je vodik ili C1-7-alkil; R3 je vodik, amino ili C1-7-alkil; R6 je vodik, halogen, C1-7-alkil, C3-6-cikloalkil, C1-7-alkil supstituiran halogenom ili C1-7- alkil supstituiran hidroksi skupinom; Z je veza, -CH2- ili -O-; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol.
7. Spoj prema bilo kojem od zahtjeva 1 do 6, naznačen time, da su spojevi sljedeći: (S)-1-(5-kloropirimidin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-N-(4-(morfolin-2-il)fenil)-1-(2-(trifluorometil)pirimidin-4-il)-1H-pirazol-4-karboksamid; (S)-1-(2-kloropirimidin-4-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-N-(4-(morfon-2-il)fenil)-1-(5-(trifluorometil)pirimidin-2-il)-1H-pirazol-4-karboksamid; (S)-1-(4-metilpirimidin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-N-(4-(morfolin-2-il)fenil)-1-(6-(trifluorometil)pirimidin-4-il)-1H-pirazol-4-karboksamid; (S)-N-(4-(morfon-2-il)fenil)-1-(2-(trifluorometil)pirimidin-5-il)-1H-pirazol-4-karboksamid; (S)-N-(4-(morfolin-2-il)fenil)-1-(4-(trifluorometil)pirimidin-2-il)-1H-pirazol-4-karboksamid; ili (S)-1-(6-ciklopropilpirimidin-4-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid.
8. Spoj formule ID prema patentnom zahtjevu 1, naznačen time, da je to: [image] gdje R2 je vodik ili C1-7-alkil; R3 je vodik, amino ili C1-7-alkil; R7 je vodik, halogen, C1-7-alkil, C3-6-cikloalkil, C1-7-alkil supstituiran halogenom, C1-7-alkil supstituiran hidroksilnom ili cijano skupinom; Z je veza, -CH2- ili -O-; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol.
9. Spoj prema bilo kojem od zahtjeva 1 do 8, naznačen time, da su spojevi sljedeći: (S)-N-(4-(morfolin-2-il)fenil)-1-(6-(trifluorometil)pirazin-2-il)-1H-pirazol-4-karboksamid; (S)-1-(6-metilpirazin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(5-metilpirazin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(3-kloropirazin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(5-cijanopirazin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(5-kloropirazin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(6-cijanopirazin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; (S)-1-(3-cijanopirazin-2-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid; ili (S)-N-(4-(morfolin-2-il)fenil)-1-(5-(trifluorometil)pirimidin-2-il)-1H-pirazol-4-karboksamid.
10. Spoj formule IE prema patentnom zahtjevu 1, naznačen time, da je to: [image] gdje R2 je vodik ili C1-7-alkil; R3 je vodik, amino ili C1-7-alkil; Z je veza, -CH2- ili -O-; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol.
11. Spoj prema bilo kojem od zahtjeva 1 ili 10, naznačen time, da spoj je (S)-1-(2,2-dihiorobenzo[d][1,3]dioksol-5-il)-N-(4-(morfolin-2-il)fenil)-1H-pirazol-4-karboksamid.
12. Spoj formule IF prema patentnom zahtjevu 1, naznačen time, da je to: [image] gdje R2 je vodik ili C1-7-alkil; R3 je vodik, amino ili C1-7-alkil; Z je veza, -CH2- ili -O-; ili njegova farmaceutski prihvatljiva kiselinska adicijska sol.
13. Spoj prema bilo kojem od zahtjeva 1 ili 12, naznačen time, da spoj je (S)-N-(4-(morfolin-2-il)fenil)-1-(4-(trifluorometil)tiazol-2-il)-1H-pirazol-4-karboksamid.
14. Postupak proizvodnje spoja formule I u skladu s bilo kojim od zahtjeva 1 do 13, naznačen time, da postupak obuhvaća cijepanje zaštitne skupine spojeva formule: [image] da bi se stvorio spoj formule I: [image] i ako je potrebno, pretvaranje dobivenih spojeva u farmaceutski prihvatljive kiselinske adicijske soli, pri čemu su supstituenti takvi kao što su opisani u zahtjevu 1.
15. Farmaceutski sastav, naznačen time, da obuhvaća spoj prema bilo kojem od patentnih zahtjeva 1 do 13, zajedno s farmaceutski prihvatljivim nosačem i/ili pomoćnom tvari.
16. Farmaceutski sastav u skladu s patentnim zahtjevom 15, naznačen time, da obuhvaća spoj prema bilo kojem od patentnih zahtjeva 1 do 13, zajedno s farmaceutski prihvatljivim nosačem i/ili pomoćnom tvari, za uporabu u liječenju depresije, poremećaja anksioznosti, bipolarnog poremećaja, hiperaktivnog poremećaja s manjkom pozornosti (ADHD), poremećaja uzrokovanih stresom, psihotičnih poremećaja, shizofrenije, neuroloških bolesti, Parkinsonove bolesti, neurodegenerativnih poremećaja, Alzheimerove bolesti, epilepsije, migrene, hipertenzije, zlouporabe droga, metaboličkih poremećaja, poremećaja hranjenja, dijabetesa, dijabetičkih komplikacija, pretilosti, dislipidemije, poremećaja potrošnje energije i asimilacije, poremećaja i nepravilnosti kod homeostaze tjelesne temperature, poremećaja spavanja i cirkadijalnog ritma, te kardiovaskularnih poremećaja.
17. Spojevi prema bilo kojem od patentnih zahtjeva 1 do 13, naznačeni time, da se upotrebljavaju kao terapeutski djelotvorne tvari.
18. Spojevi prema bilo kojem od patentnih zahtjeva 1 do 13, naznačeni time, da se upotrebljavaju u liječenju depresije, poremećaja anksioznosti, bipolarnog poremećaja, hiperaktivnog poremećaja s manjkom pozornosti (ADHD), poremećaja uzrokovanih stresom, psihotičnih poremećaja, shizofrenije, neuroloških bolesti, Parkinsonove bolesti, neurodegenerativnih poremećaja, Alzheimerove bolesti, epilepsije, migrene, hipertenzije, zlouporabe droga, metaboličkih poremećaja, poremećaja hranjenja, dijabetesa, dijabetičkih komplikacija, pretilosti, dislipidemije, poremećaja potrošnje energije i asimilacije, poremećaja i nepravilnosti kod homeostaze tjelesne temperature, poremećaja spavanja i cirkadijalnog ritma, te kardiovaskularnih poremećaja.
19. Uporaba spoja prema bilo kojem od patentnih zahtjeva 1 do 13, naznačena time, da je za proizvodnju lijekova za terapeutsko i/ili profilaktičko liječenje depresije, poremećaja anksioznosti, bipolarnog poremećaja, hiperaktivnog poremećaja s manjkom pozornosti (ADHD), poremećaja uzrokovanih stresom, psihotičnih poremećaja, shizofrenije, neuroloških bolesti, Parkinsonove bolesti, neurodegenerativnih poremećaja, Alzheimerove bolesti, epilepsije, migrene, hipertenzije, zlouporabe droga, metaboličkih poremećaja, poremećaja hranjenja, dijabetesa, dijabetičkih komplikacija, pretilosti, dislipidemije, poremećaja potrošnje energije i asimilacije, poremećaja i nepravilnosti kod homeostaze tjelesne temperature, poremećaja spavanja i cirkadijalnog ritma, te kardiovaskularnih poremećaja.
HRP20171981TT 2012-09-14 2013-09-11 Derivati pirazolkarboksamida kao taar modulatora za uporabu u liječenju nekoliko poremećaja poput depresije, dijabetesa i parkinsonove bolesti HRP20171981T1 (hr)

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CN110291084A (zh) 2016-12-15 2019-09-27 加利福尼亚大学董事会 用于治疗癌症的组合物和方法
US20220340597A1 (en) 2019-04-09 2022-10-27 Hoffmann-La Roche Inc. Hexahydro-1h-pyrazino[1,2-a]pyrazine compounds for the treatment of autoimmune disease
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GB9425211D0 (en) 1994-12-14 1995-02-15 Ucb Sa Substituted 1H-imidazoles
GB9520150D0 (en) 1995-10-03 1995-12-06 Orion Yhtymae Oy New imidazole derivatives
US6841684B2 (en) 1997-12-04 2005-01-11 Allergan, Inc. Imidiazoles having reduced side effects
MX2009008465A (es) 2007-02-15 2009-08-20 Hoffmann La Roche Nuevas 2-aminooxazolinas como ligandos de taar1.
US9452980B2 (en) * 2009-12-22 2016-09-27 Hoffmann-La Roche Inc. Substituted benzamides
TW201236685A (en) * 2010-11-11 2012-09-16 Daiichi Sankyo Co Ltd New pyrazole amide derivatives
US9073911B2 (en) * 2011-06-09 2015-07-07 Hoffmann-La Roche Inc. Pyrazole derivatives
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