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SI3065738T1 - Sestavki in postopki za moduliranje farnezoidnih X receptorjev - Google Patents

Sestavki in postopki za moduliranje farnezoidnih X receptorjev Download PDF

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SI3065738T1
SI3065738T1 SI201430692T SI201430692T SI3065738T1 SI 3065738 T1 SI3065738 T1 SI 3065738T1 SI 201430692 T SI201430692 T SI 201430692T SI 201430692 T SI201430692 T SI 201430692T SI 3065738 T1 SI3065738 T1 SI 3065738T1
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methyl
carboxamido
pyrazole
dihydrochromeno
chloro
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David Tully
Donatella Chianelli
Xiaodong Liu
Valentina Molteni
John Nelson
Jason Roland
Paul Rucker
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Novartis Ag
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Claims (21)

  1. Sestavki in postopki za moduliranje famezoidnih X receptorjev Patentni zahtevki
    1. Spojina s formulo (I),
    ali njena farmacevtsko sprejemljiva sol, kjer R° je obroč A ali Ci_6 alkil; obroč A je aril; 5-10 členski heteroaril, ki obsega 1-3 N, O ali S heteroatome; ali C3.7 cikloalkil; in navedeni obroč A je nesubstituiran ali substituiran z 1-2 substituentoma, Λ neodvisno predstavljenima z R ; obroč B je aril; 5-10 členski heteroaril, ki obsega 1-3 N, O ali S heteroatome; ali C3.7 cikloalkil; in navedeni obroč B je nesubstituiran ali substituiran z 1-2 substituentoma, Λ neodvisno predstavljenima z R ; Xje-(CR4R5)-; Y je -O-, -(CR4R5)- ali *-0(CR4R5)-, kjer * označuje točko vezave Y na obroč, ki vsebuje Z obročne atome; Z1, Z2, Z3 in Z4 so vsak neodvisno -CR3- ali -N-; L1 je ''-(CR^5)^-, kjer "M" označuje točko vezave L1 na N; L2 je *2-(CR4R5)!.2-, *2-(CR4R5)-C(0)-NR-, *2-(CR4R5)2-0-, *2-(CR4R5)2-NR- ali *2-(CR4R5)-C(0)-NR-(CR4R5)-; kjer "*2" označuje točko vezave L2 na N; L3 je -C(O)-; vsak R2 je neodvisno halo, Ci.6 alkil ali halo-substituiran Ci_6 alkil; vsak R3 je neodvisno vodik, halo ali Ci.6 alkil; R,R4inR5 so neodvisno vodik ali Ci.$ alkil.
  2. 2. Spojina po zahtevku 1, kjer ima spojina formulo (II):
    ali njena farmacevtsko sprejemljiva sol; kjer R° je obroč A ali C^alkil; kjer je obroč A fenil, piridil ali ciklopropil, od katerih je vsak nesubstituiran ali substituiran z 1-2 substituentoma, neodvisno predstavljenima z R2; obroč B je izbran izmed fenila, piridila, 1/f-indolila in C3.7 cikloalkila, od katerih je vsak nesubstituiran ali substituiran z 1-2 substituentoma, neodvisno predstavljenima z R2; X je -(CR4R5)-; Y je -O-, -(CR4R5)- ali *-0(CR4R5)-, kjer * označuje točko vezave Y na obroč, ki vsebuje Z obročne atome; Z1, Z2, Z3 in Z4 so vsak neodvisno -CR3- ali -N-; L' je ''-(CRV),^, kjer "*r označuje točko vezave L1 na N; L2 je *2_(CR4R5)1.2“, *2-(CR4R5)-C(0)-NR-, *2-(CR4R5)2-0-, *2-(CR4R5)2-NR- ali *2-(CR4R5)-C(0)-NR-(CR4R5)-; kjer *2 označuje točko vezave L2 na N; vsak R2 je neodvisno halo, Ci_6alkil ali halo-substituiran Ci_6alkil; vsak R3 je neodvisno vodik, halo ali Ci_6alkil; in R,R4inR5 so neodvisno vodik ali Ci^alkil.
  3. 3. Spojina po zahtevku 1 ali 2, kjer je R° izbran izmed *3-CH2C(CH3)2-, *3-CH2CH(CH3)- in *3-ciklopropan-1,1 ,-diila, kjer *3 označuje točko vezave R° na L2.
  4. 4. Spojina po zahtevku 1 ali 2, kjer ima spojina formulo (III):
    ali njena farmacevtsko sprejemljiva sol; kjer obroč A je fenil ali piridil, od katerih je vsak nesubstituiran ali substituiran z 1-2 substituentoma, neodvisno predstavljenima z R2; obroč B je izbran izmed fenila, piridila, 1/f-indolila in ciklopentila, od katerih je vsak nesubstituiran ali substituiran z 1-2 substituentoma, neodvisno predstavljenima z R2; L1 je -(CR4R5)-; L2 je izbran izmed -(CH2)-, *2-CH2C(0)NH-, ’2-CH(CH3)C(0)NH-, *2-CH2C(0)NHCH2-, *2-(CH2)20- in *2-(CH2)2NH-; kjer *2 označuje točko vezave L2 na N; Xje CH2; Y je izbran izmed -O-, -CHr, -C(CH3)2- in *-0-CHr, kjer * označuje točko vezave Y na obroč, ki vsebuje Z obročne atome; Z1 je CR3 ali N; Z2 je CR3; Z3 je CR3; Z4 je CR3 ali N; vsak R je neodvisno izbran izmed halo, metila in trifluorometila; vsak R3 je neodvisno vodik, halo ali Ci_6alkil; in vsak od R4 in R5 je neodvisno vodik ali metil.
  5. 5. Spojina po katerem koli od zahtevkov od 1 do 4, kjer je L2 izbran izmed -(CH2) -, *2-CH2C(0)NH-, *2-(CH2)20- in *2-(CH2)2NH-; kjer "*2" označuje točko vezave L2 na N.
  6. 6. Spojina po katerem koli od zahtevkov od 1 do 5, kjer je vsak R2 neodvisno fluoro ali metil.
  7. 7. Spojina po katerem koli od zahtevkov od 1 do 6, kjer je vsak R3 neodvisno izbran izmed vodika, fluoro, kloro in metila.
  8. 8. Spojina po katerem koli od zahtevkov od 1 do 7, kjer Z1 je izbran izmed CH, CF, CCH3 in N; Z2 je izbran izmed CH, CF, CC1 in CCH3; Z3 je izbran izmed CH, CF, CC1 in CCH3; in Z4 je CH ali N.
  9. 9. Spojina po zahtevku 1, kjer ima navedena spojina formulo (IV):
    ali njena farmacevtsko sprejemljiva sol; kjer vsak fenilni obroč je po izbiri nadalje substituiran z 1-2 substituentoma, neodvisno predstavljenima z R2, kjer R2 je fluoro ali metil; L2 je izbran izmed -CH2-, *2-CH2CH2NH-, *2-CH2CH20- in *2-CH2C(0)NH-, kjer "*2" označuje točko vezave L2 na N; Z2 je izbran izmed CH, CF, CC1 in CCH3; in Z3 je izbran izmed CH, CF, CC1 in CCH3.
  10. 10. Spojina po zahtevku 1, izbrana izmed naslednjih: 4-fhioro-3-(2-(8-fhioro-N-(2-fhiorobenzil)-1 -metil-1,4-dihidrokromeno[4,3- c]pirazol-3-karboksamido)acetamido)benzojska kislina; 4-fhioro-3-(2-(8-fhioro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3 - c]pirazol-3-karboksamido)acetamido)benzojska kislina; 3- (2-(8-kloro-1 -metil-N-(3-metilbenzil)-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzojska kislina; 4- fhioro-3-(2-(l-metil-N-(3-metilbenzil)-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 3-(2-(N-(2-fluorobenzil)-1,8-dimetil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 3-(2-(N-(2-fluorobenzil)-1,6-dimetil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(8-fluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(7-fluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(7-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(6,8-difluoro-N-(2-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol- 3-karboksamido)acetamido)benzojska kislina; 3-(2-(N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-1,7-dimetil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-1,6-dimetil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3- (2-(8-kloro-6-fluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 4- fluoro-3-(2-(N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(7,8-difluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol- 3-karboksamido)acetamido)-4-fluorobenzojska kislina; 3-(2-(7,8-difluoro-N-(3-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol- 3-karboksamido)acetamido)-4-fluorobenzojska kislina; 3- (2-(N-benzil-7,8-difluoro-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzojska kislina; 4- fluoro-3-(2-(8-fluoro-l-metil-N-(3-metilbenzil)-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 4-fluoro-3-(2-(N-(2-fluorobenzil)-l-metil-4,5-dihidro-lH-pirazolo[4,3-h]kinolin- 3- karboksamido)acetamido)benzojska kislina; 4- fluoro-3-(2-(N-(2-fluorobenzil)-1 -metil-4,5-dihidro-1 H-pirazolo[3,4-f]kinolin- 3-karboksamido)acetamido)benzojska kislina; (S)-4-fluoro-3-(2-(8-fluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)propanamido)benzojska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-1 -metil-4,5-dihidro- lH-benzo[g]indazol-3-karboksamido)acetamido)benzojska kislina; 3- (2-(8-kloro-7-fluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 4- fluoro-3-(2-(N-(3-fluorobenzil)-1,5,5-trimetil-4,5-dihidro- lH-benzo[g]indazol- 3- karboksamido)acetamido)benzojska kislina; 4- fluoro-3-(2-(N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 3-(2-(8-kloro-N-(3-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzoj ska kislina; 3-(2-(N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzoj ska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzoj ska kislina; 3-(2-(N-benzil-8-kloro-1-metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 3-(2-(N-benzil-8-fluoro-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzoj ska kislina; 3-(2-(N-benzil-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzojska kislina; 3-(2-(9-kloro-N-(2-fluorobenzil)-l-metil-4,5-dihidro-lH-benzo[2,3]oksepino[4,5-c]pirazol-3 -karboksamido)acetamido)-4-fluorobenzoj ska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzoj ska kislina; 3-(2-(8-kloro-N-(ciklopentilmetil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-fluorobenzoj ska kislina; 3-(2-(8-kloro-N-(ciklopentilmetil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)benzojska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-5-fluorobenzojska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-4-metilbenzojska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-2-metilpropanojska kislina; 3- (2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)-2,2-dimetilpropanoj ska kislina; 1 -((2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)metil)ciklopropankarboksilna kislina; 4- (2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-fluorobenzoj ska kislina; 3- (2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)benzoj ska kislina; 4- (2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)benzoj ska kislina; N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-metilbenzojska kislina; 4-(2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3,5-dimetilbenzojska kislina; 3- (2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-4-fluorobenzoj ska kislina; 4- (2-(8-kloro-N-(ciklopentilmetil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3,5-dimetilbenzojska kislina; 4-(2-(8-kloro-N-(2-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3,5-difluorobenzojska kislina; 4-(2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-(trifluorometil)benzojska kislina; 4-(2-(N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3,5-difluorobenzojska kislina; 3,5-difluoro-4-(2-(8-fluoro-N-(2-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)benzojska kislina; 4-(2-(N-benzil-8-fluoro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3,5-difluorobenzojska kislina; 4-(2-(N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-fluorobenzojska kislina; 4-(2-(N-benzil-8-fluoro-1-metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-fluorobenzojska kislina; 4-(2-(N-benzil-7,8-difluoro-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-fluorobenzojska kislina; 3- fluoro-4-(2-(8-fluoro-N-(3-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)benzojska kislina; 4- (2-(7,8-difluoro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol- 3- karboksamido)etoksi)-3-£luorobenzojska kislina; 4- (2-(8-kloro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-fluorobenzojska kislina; 3- fluoro-4-(2-(8-fluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)benzojska kislina; 4- (2-(7,8-difluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etoksi)-3-fluorobenzojska kislina; 3-((2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)benzoj ska kislina; 3-(2-(8-kloro-N-(2-fluorobenzil)-1-metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)acetamido)- 4-fluorobenzojska kislina; 3-((2-(8-kloro-N-(3-fluorobenzil)-1-metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)-4-fluorobenzojska kislina; 3- ((2-(8-kloro-1 -metil-N-(3-metilbenzil)-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)-4-fluorobenzojska kislina; 4- fluoro-3-((2-(8-fluoro-1 -metil-N-(3-metilbenzil)-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)benzojska kislina; 3-((2-(7,8-difluoro-l-metil-N-(3-metilbenzil)-l,4-dihidrokromeno[4,3-c]pirazol- 3- karboksamido)etil)amino)-4-fluorobenzojska kislina; 4- fluoro-3-((2-(8-fluoro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)benzojska kislina; 4-fluoro-3-((2-(N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)benzoj ska kislina; 3-((2-(N-benzil-8-fluoro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)-4-fluorobenzoj ska kislina; 3-((2-(N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)-4-fluorobenzojska kislina; 3-((2-(7,8-difluoro-N-(3-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)-4-fluorobenzojska kislina; 3- ((2-(N-benzil-7,8-difluoro-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)-4-fluorobenzoj ska kislina; 4- ((N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-3-fluorobenzojska kislina; 4-((8-fluoro-N-(3-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((8-kloro-N-(3,5-difluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((N-benzil-8-fluoro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-3 -fluorobenzoj ska kislina; 4-((8-kloro-1 -metil-N-(3-metilbenzil)-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzoj ska kislina; 4-((8-kloro-N-(2,3-difluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzoj ska kislina; 4-((8-kloro-N-(3-fluoro-5-metilbenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol- 3- karboksamido)metil)benzojska kislina; 4- ((N-(3,5-difluorobenzil)-8-fluoro-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzoj ska kislina; 4-((8-kloro-1 -metil-N-(3 -metilbenzil)-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-3-fluorobenzojska kislina; 3- fluoro-4-((8-fluoro-1 -metil-N-(3-metilbenzil)-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4- ((N-(( 1 H-indol-5-il)metil)-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 5- ((8-kloro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)pikolinska kislina; 4-((8-kloro-N-((5-fluoropiridin-3-il)metil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((8-kloro-N-((5-kloropiridin-3-il)metil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((8-kloro-N-(3-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-2-fluorobenzojska kislina; 4-((N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-2-fluorobenzojska kislina; N-benzil-N-(4-karbamoilbenzil)-8-kloro-1-metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamid; 4-((8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-3-fluorobenzojska kislina; 3-£luoro-4-((8-fluoro-N-(2-fluorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((8-kloro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojska kislina; 4-((8-kloro-N-(3-fhiorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-3-fluorobenzojska kislina; 4- ((8-kloro-N-(2-fhiorobenzil)-l-metil-l,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-2-fluorobenzoj ska kislina; 6-((8-kloro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)nikotinska kislina; 5- ((8-kloro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)-6-metilpikolinska kislina; 4-fluoro-3-((2-(8-fluoro-N-(3-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)benzojska kislina; in 3-((2-(8-kloro-N-(2-fluorobenzil)-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)etil)amino)-4-fluorobenzojska kislina; ali njena farmacevtsko sprejemljiva sol.
  11. 11. Spojina po zahtevku 1 ali njena farmacevtsko sprejemljiva sol, kjer je navedena spoj ina 4-((N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3- karboksamido)metil)benzojska kislina.
  12. 12. Spojina po zahtevku 11, ki je TRIS sol 4-((N-benzil-8-kloro-1-metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojske kisline.
  13. 13. Spojina po zahtevku 11, ki je megluminska monohidratna sol 4-((N-benzil-8-kloro-1 -metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojske kisline.
  14. 14. Spojina po zahtevku 11, kije megluminska sol 4-((N-benzil-8-kloro-l-metil-1,4-dihidrokromeno[4,3-c]pirazol-3-karboksamido)metil)benzojske kisline.
  15. 15. Spojina s formulo (V):
    kjer je vsak fenilni obroč po izbiri nadalje substituiran z 1-2 substituentoma, neodvisno predstavljenima z R2, Λ kjer je R fluoro ali metil; L2 je izbran izmed -CH2-, *2-CH2CH2NH-, *2-CH2CH20- in *2-CH2C(0)NH-, kjer *2 označuje točko vezave L2 na N; Z2 je izbran izmed CH, CF, CC1 in CCH3; Z3 je izbran izmed CH, CF, CC1 in CCH3; in R6 je Ci.6 alkil.
  16. 16. Farmacevtski sestavek, ki obsega terapevtsko učinkovito količino spojine po katerem koli od zahtevkov 1-14 in farmacevtsko sprejemljiv nosilec.
  17. 17. Kombinacija, ki obsega terapevtsko učinkovito količino spojine po katerem koli od zahtevkov 1-14 in drugo terapevtsko sredstvo.
  18. 18. Spojina po katerem koli od zahtevkov 1-14 za uporabo v zdravljenju stanja, posredovanega z FXR, kjer je navedeno stanje, posredovano z FXR, bolezen jeter, izbrana izmed intrahepatične holestaze, z estrogeni inducirane holestaze, z zdravilom inducirane holestaze, nosečniške holestaze, s parenteralno prehrano povezane holestaze, progresivne familiame holestaze (PFIC), Alagillejevega sindroma, primarne biliame ciroze (PBC), primarnega sklerozirajočega holangitisa, duktopenične zavrnitve jetrnega transplantata, z jetrnim transplantatom povezane bolezni presadek proti gostitelju, cistične fibrozne jetrne bolezni, nealkoholne maščobne jetrne bolezni (NAFLD), nealkoholnega steatohepatitisa (NASH), alkoholne jetrne bolezni in s parenteralno prehrano povezane jetrne bolezni; ali gastrointestinalne bolezni, izbrane izmed malabsorbcije žolčne kisline, žolčnega refluksnega gastritisa in vnetne črevesne bolezni.
  19. 19. Spojina po katerem koli od zahtevkov 1-14 za uporabo v zdravljenju stanja, posredovanega z FXR, kjer je navedeno stanje, posredovano z FXR, gastrointestinalna bolezen, izbrana izmed malabsorbcije žolčne kisline, žolčnega refluksnega gastritisa in vnetne črevesne bolezni.
  20. 20. Spojina za uporabo po zahtevku 18, kjer je navedeno Stranje, posredovano z FXR, nealkoholna maščobna jetrna bolezen (NAFLD) ali nealkoholni steatohepatitis (NASH).
  21. 21. Spojina po katerem koli od zahtevkov 1-14 za uporabo v zdravljenju diabetične nefropatije.
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Families Citing this family (34)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2545964A1 (en) 2011-07-13 2013-01-16 Phenex Pharmaceuticals AG Novel FXR (NR1H4) binding and activity modulating compounds
AP2016009165A0 (en) 2013-11-05 2016-04-30 Novartis Ag Compositions and methods for modulating farnesoid x receptors
TWI698430B (zh) 2015-02-13 2020-07-11 南北兄弟藥業投資有限公司 三環化合物及其在藥物中的應用
EP3288948B1 (en) * 2015-04-30 2019-11-20 Novartis AG Fused tricyclic pyrazole derivatives useful for modulating farnesoid x receptors
US11344540B2 (en) 2016-02-22 2022-05-31 Novartis Ag Methods for treating liver disorders using FXR agonists
EA037744B1 (ru) 2016-06-13 2021-05-17 Джилид Сайэнс, Инк. Соединения, модулирующие fxr (nr1h4)
CA2968836A1 (en) 2016-06-13 2017-12-13 Gilead Sciences, Inc. Fxr (nr1h4) modulating compounds
JOP20190040A1 (ar) * 2016-09-14 2019-03-10 Novartis Ag توليفة من ناهضات fxr
EP3512514A1 (en) * 2016-09-14 2019-07-24 Novartis AG Novel regimes of fxr agonists
CA3039283A1 (en) * 2016-10-05 2018-04-12 Novartis Ag Combination compositions comprising fxr agonists for treating or preventing a fibrotic,cirrhotic disease or disorder
CN107973790A (zh) * 2016-10-22 2018-05-01 合帕吉恩治疗公司 杂环fxr调节剂
PL3600309T3 (pl) 2017-03-28 2022-11-07 Gilead Sciences, Inc. Skojarzenia terapeutyczne do leczenia chorób wątroby
WO2018226155A1 (en) * 2017-06-05 2018-12-13 National University Of Singapore Compounds useful in inhibiting human trefoil factor 3
EP3668599A1 (en) 2017-08-15 2020-06-24 Inflazome Limited Sulfonylureas and sulfonylthioureas as nlrp3 inhibitors
EP3668842A1 (en) 2017-08-15 2020-06-24 Inflazome Limited Sulfonylureas and sulfonylthioureas as nlrp3 inhibitors
WO2019034693A1 (en) 2017-08-15 2019-02-21 Inflazome Limited SULFONYLURATES AND SULFONYLTHIOURES AS INHIBITORS OF NLRP3
US20200276178A1 (en) * 2017-09-13 2020-09-03 Novartis Ag Combinations comprising fxr agonists
MX2020004423A (es) 2017-11-09 2020-08-06 Inflazome Ltd Nuevos compuestos de sulfonamida carboxamida.
CN110128432B (zh) * 2018-02-02 2021-03-02 广东东阳光药业有限公司 含氮三环化合物及其在药物中的应用
US11905252B2 (en) 2018-03-02 2024-02-20 Inflazome Limited Compounds
PE20210406A1 (es) 2018-07-25 2021-03-02 Novartis Ag Inhibidores de inflamasoma nlrp3
MX2021008518A (es) 2019-01-15 2021-08-19 Gilead Sciences Inc Compuestos que modulan fxr(nr1h4).
US10610280B1 (en) 2019-02-02 2020-04-07 Ayad K. M. Agha Surgical method and apparatus for destruction and removal of intraperitoneal, visceral, and subcutaneous fat
JP2022519906A (ja) 2019-02-19 2022-03-25 ギリアード サイエンシーズ， インコーポレイテッド Ｆｘｒアゴニストの固体形態
AR119731A1 (es) 2019-05-17 2022-01-05 Novartis Ag Inhibidores del inflamasoma nlrp3
KR20220035365A (ko) 2019-07-18 2022-03-22 엔요 파마 인터페론의 부작용을 감소시키는 방법
TW202122078A (zh) 2019-09-06 2021-06-16 瑞士商諾華公司 使用lta4h抑制劑治療肝臟疾病之方法
IL293892A (en) 2020-01-15 2022-08-01 Inserm Institut National De La Sant? Et De La Rech M?Dicale Use of fxr agonists to treat hepatitis d virus infection
CN113387828A (zh) * 2020-03-14 2021-09-14 江巨东 一种阿利克仑中间体的制备方法
WO2022037663A1 (zh) * 2020-08-21 2022-02-24 苏州晶云药物科技股份有限公司 苯甲酸衍生物的新晶型及其制备方法
WO2022152770A1 (en) 2021-01-14 2022-07-21 Enyo Pharma Synergistic effect of a fxr agonist and ifn for the treatment of hbv infection
JP2024517181A (ja) 2021-04-28 2024-04-19 ウエヌイグレックオ・ファーマ 組合せ治療としてｆｘｒアゴニストを使用するｔｌｒ３アゴニストの効果の強い増強
TW202406550A (zh) 2022-08-03 2024-02-16 瑞士商諾華公司 Ｎｌｒｐ３炎性小體抑制劑
WO2024044778A2 (en) * 2022-08-26 2024-02-29 Celmatix Inc. Novel modulators of fshr and uses thereof

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20050143449A1 (en) * 2002-11-15 2005-06-30 The Salk Institute For Biological Studies Non-steroidal farnesoid X receptor modulators and methods for the use thereof
CA2651378C (en) 2006-05-24 2012-08-28 Eli Lilly And Company Fxr agonists
US7486960B2 (en) * 2006-09-15 2009-02-03 Thales Avionics, Inc. System and method for wirelessly transferring content to and from an aircraft
TW200906823A (en) * 2007-07-16 2009-02-16 Lilly Co Eli Compounds and methods for modulating FXR
CU24152B1 (es) * 2010-12-20 2016-02-29 Irm Llc 1,2 oxazol-8-azabiciclo[3,2,1]octano 8 il como moduladores de fxr
AP2016009165A0 (en) 2013-11-05 2016-04-30 Novartis Ag Compositions and methods for modulating farnesoid x receptors
EP3288948B1 (en) 2015-04-30 2019-11-20 Novartis AG Fused tricyclic pyrazole derivatives useful for modulating farnesoid x receptors

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