HRP20170019T1 - Novi pirol-inhibitori od reduktaze s-nitrozoglutationa kao terapeutska sredstva - Google Patents

Novi pirol-inhibitori od reduktaze s-nitrozoglutationa kao terapeutska sredstva Download PDF

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Publication number
HRP20170019T1
HRP20170019T1 HRP20170019TT HRP20170019T HRP20170019T1 HR P20170019 T1 HRP20170019 T1 HR P20170019T1 HR P20170019T T HRP20170019T T HR P20170019TT HR P20170019 T HRP20170019 T HR P20170019T HR P20170019 T1 HRP20170019 T1 HR P20170019T1
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Croatia
Prior art keywords
phenyl
pyrrol
propanoic acid
methylphenyl
carbamoyl
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HRP20170019TT
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English (en)
Inventor
Jan Wasley
Gary J. Rosenthal
Xicheng Sun
Sarah Strong
Jian Qiu
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Nivalis Therapeutics, Inc.
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Publication of HRP20170019T1 publication Critical patent/HRP20170019T1/hr

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Description

NOVI PIROL-INHIBITORI OD REDUKTAZE S-NITROZOGLUTATIONA KAO TERAPEUTSKA SREDSTVA

Claims (30)

1. Spoj, naznačen time, da ima sljedeću formulu I, ili njegova farmaceutski prihvatljiva sol: [image] u kojoj Ar je odabran iz skupine koju čine: ari I, supstituirani aril, heteroaril i supstituirani heteroaril, pri čemu je aril 5-člani do 14-člani monociklički, biciklički ili triciklički aromatski sustav prstena; i heteroaril je aromatski heterociklički prsten od 5 do 14 članova, koji ima najmanje jedan heteroatom odabran od dušika, kisika i sumpora, te sadrži najmanje jedan ugljikov atom, uključujući monocikličke, bicikličke i tricikličke sustave prstena, gdje su supstituenti za aril i heteroaril odabrani iz skupine koju čine: -halo, -ORe', -OC(O)Re'-NRe'Re", -SRe",-Re',-CN,-NO2, -CO2Re',-C(O)NRe'Re"-C(O)Re',-OC(O)NRe'Re", -NRe"c(O)Re', -NRe"C02Re', -NRe"c(O)NRe'Re'', -NRe"SO2NRe'Re", -NHC(NH2)=NH, -NReC(NH2)=NH, NH-C(NH2)=NRe', -S(O)Re', -SO2Re', -SO2NReRe", -NRe"SO2Re', -N3 -CH(Ph)2, perfluoroalkoksi i perfluoro(C1-C4)alkil, u količini koja ide rasponu od nula do ukupnog broja otvorenih valencija na aromatskom sustavu prstena; i pri čemu su Re, Re i Re neovisno odabrani od sljedećih: vodik, nesupstituirani (C1-C8)alkil, nesupstituirani hetero(C1-C8)alkil, nesupstituirani aril, nesupstituirani heteroaril, nesupstituirani aril(C1-C4)alkil, nesupstituirani ariloksi(C1-C4)alkil, monosupstituirani aril i monosupstituirani heteroaril; R1 je odabran iz skupine koju čine: vodik, C1-C6 alkil, C3-C6cikloalkii, aril, supstituirani aril, heteroaril i supstituirani heteroaril, gdje su aril, heteroaril i supstituenti za aril i heteroaril prethodno definirani; R2 je odabran iz skupine koju čine: halogen, C1-C6alkil, C3-C6 cikloalkii, cijano, nitro, CF3, karbamoil, C1-C6alkilkarbamoil, amino, C1-C6alkilamino, C1-C6dialkilamino, C1-C6alkoksi i C3-C6cikloalkoksil; R3 je odabran iz skupine koju čine: hidroksil, karbamoil, C1-C6alkilkarbamoil, sulfamoil, C1-C6alklisuIfamoil, C3-C6cikloalkii, cijano, nitro, karboksil, amino, aminometil, acetamido, acetamido-2-metil, 2-metoksiacetamido, propionamido, tetrahidrofuran-2-ilmetoksi, CF3, karboksil, ureido, sulfamoilamino, C1-C6alkilsulfonamido, 2-amino-2-oksoetil, C1-C6alkilamino, C1-C6dialkilamino, arilamino, heteroarilamino, C1-C6alkoksil, C3-C6cikloalkoksil, 1H-imidazol-2-il, oksazol-2-il, tiazol-2-il, metilkarbamoil, dimetilkarbamoil, metoksi etilkarbamoil, hidroksietilkarbamoil, (dimetilamino)etilkarbamoil, piridin-3-ilkarbamoil, piridin-4-il-karbamoil, 6-metoksipiridin-3-ilkarbamoil, piridazin-4-ilkarbamoil i pirimidin-5-il-karbamoil; R4 je odabran iz skupine koju čine: vodik, hidroksil, halogen, C1-C6alkil, C3-C6cikloalkil, cijano, nitro, karbamoil, C1-C6alkilkarbamoil, sulfamoil, C1-C6alkilsulfamoil, amino, C1-C6alkilamino, C1-C6dialkilamino, C1-C6alkoksil i C3-C6cikloalkoksil; n je 0-3; gdje Ar isključuje supstituirani ili nesupstituirani indazol-3-il i supstituirani ili nesupstituirani 1H-pirazolo[3,4-b]piridil; sa sljedećim uvjetima: uvjet Ia: kada R3 je karboksil, metilsulfonamido ili sulfamoil, tada Ar ne može biti fenil, ni supstituirani ili nesupstituirani fenil-(C1-C3)-alkil, niti fenil-(C2-C6)-alkenil; i uvjet Ib: kada su oba R2 i R3 metoksi, tada Ar ne može biti fenil, 4-metil-fenil, 4-metoksi-fenil, 4-halo-fenil, ni tiofen-il.
2. Spoj prema zahtjevu 1, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da: Ar je odabran iz skupine koju čine: fenil, supstituirani fenil, tiofen-il, supstituirani tiofen-il, piridinil, supstituirani piridinil, tiazolil, supstituirani tiazolil, pirimidinil, supstituirani pirimidinil, furanil, supstituirani furanil, biciklički aril, supstituirani biciklički aril, biciklički heteroaril i supstituirani biciklički heteroaril; R1 je odabran iz skupine koju čine vodik i C1-C6alkil; R2 je odabran iz skupine koju čine halogen, C1-C6alkil i CF3; R3 je odabran iz skupine koju čine: hidroksil, karbamoil, sulfamoil, sulfamoilamino, C1-C6alkoksi, amino, aminometil, acetamido, acetamido-2-metil, 2-metoksiacetamido, propionamido, tetrahidrofuran-2-ilmetoksi, metilsulfamido, karboksil, C1-C6alkilamino, 1H-imidazol-2-il, oksazol-2-il, tiazol-2-il, metilkarbamoil, dimetilkarbamoil, metoksietilkarbamoil, hidroksietilkarbamoil, (dimetilaminojetilkarbamoil, piridin-3-ilkarbamoil, piridin-4-il-karbamoil, 6-metoksipiridin-3-ilkarbamoil, piridazin-4-ilkarbamoil i pirimidin-5-ilkarbamoil; R4 je odabran iz skupine koju čine: vodik i C1-C6alkil; i n je 1.
3. Spoj prema zahtjevu 1 ili zahtjevu 2, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da: Ar je odabran iz skupine koju čine: fenil, supstituirani fenil, aril-fenil, supstituirani aril-fenil, heteroaril-fenil, supstituirani heteroaril-fenil, tiofen-il, supstituirani tiofen-il, aril-tiofen-il, supstituirani aril-tiofen-il, heteroaril-tiofen-il, supstituirani heteroaril-tiofen-il, piridinil, supstituirani piridinil, aril-piridinil, supstituirani aril-piridinil, heteroaril-piridinil, supstituirani heteroaril-piridinil, tiazolil, supstituirani tiazolil, aril-tiazolil, supstituirani aril-tiozolil, heteroaril-tiazolil, supstituirani heteroaril-tiazolil, pirimidinil, supstituirani pirimidinil, aril-pirimidinil, supstituirani aril-pirimidinil, heteroaril-pirimidinil, supstituirani heteroaril-pirimidinil, furanil, supstituirani furanil, aril-furanil, supstituirani aril-furanil, heteroaril-furanil i supstituirani heteroaril-furanil.
4. Spoj prema zahtjevu 1 ili zahtjevu 2, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da: Ar je odabran iz skupine koju čine: fenil, tiofen-il, tiazolil, piridinil, pirimidinil, i furanil koji ima 0, 1, 2, ili 3 supstitucije, pri čemu su takve supstitucije neovisno odabrane iz skupine koju čine: vodik, hidroksil, halogen, C1-C6alkoksi, amino, cijano, C1-C6alkil, imidazolil, metilimidazolil, etilimidazolil, furanil, metiltio, nitro, triazolil, tetrazolil, karbamoil, pirazolil, trifluorometoksi, trifluorometil, 2-amino-2-oksoetoksi, ureido, morfolino, piridinil, pirolil, metilsulfonamido, karbamoil-fenil, 6-okso-l,6-dihidropiridinil, 3,5-dimetilizoksazolil, karboksimetoksi, hidroksiacetamido, metoksiacetamido, sulfamoil, piperazinil, oksoimidazolidinil, metilsulfinil, metilsulfonil, pirolidinil, piperidinil, metilpirazolil, fenil, tiazolil, hidroksikarbamoil, ciklopropilimidazolil, karboksi, metilamino, metoksimetil, dimetilamino, hidroksimetilimidazolil, oksooksazolidinil, formamido, hidroksifenil i tiofen-il.
5. Spoj prema zahtjevu 1 ili zahtjevu 2, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da: Ar je odabran iz skupine koju čine: 4-(1H-imidazol-1-il)fenil, 5-(1H-imidazol-1-il)tiofen-2-il, 4-(2-metil-1H-imidazol-1-il)fenil, tiazol-5-il, 4-hidroksifenil, 5-bromotiofen-2-il, 4-metoksifenil, 4-aminofenil, 4-bromofenil, 4-(furan-3-il)fenil, fenil, 3-kloro-4-metoksifenil, 3-fluoro-4-metoksifenil, 4-cijanofenil, 3-kloro-4-hidroksifenil, 4-metoksi-3-metilfenil, 4-jodofenil, 3-metoksifenil, 6-metoksipiridin-3-il, benzo[d]tiazol-6-il, 4-(metiltio)fenil, 4-nitrofenil, 4-(4H-1,2,4-triazol-4-il)fenil, 4-(2H-tetrazol-5-il)fenil, benzo[d][1,3]dioksol-5-il, 6-(1H-imidazol-1-il)piridin-3-il, 5-karbamoiltiofen-2-il, 4-(1H-pirazol-4-il)fenil, 4-(trifluorometoksi)fenil;4-karbamoil-fenil, 4-(trifluorometil)fenil, 4-(1H-1,2,4-triazol-1-il)fenil,4-(1H-pirazol-1-il)fenil, 4-(2-amino-2-oksoetoksi)fenil,4-(l-metil-1H-pirazol-4-il)fenil, 4-(1H-tetrazol-1-il)fenil, 4-(4-metil-1H-imidazol-1-il)fenil, 4-ureidofenil, 4-morfolinofenil, 4-(2H-tetrazol-5-il)fenil, 4-(piridin-4-il)fenil# 4-(1H-pirol-1-il)fenil, 4-(metilsulfonamido)fenil, 1H-l,2;3-triazol-1-il)fenil, naftalen-2-il, 3'-karbamoilbifenil-4-il; 4-(6-okso-l,6-dihidropiridin-3-il)fenil;4-(3;5-dimetilizoksazol-4-il)fenil, 4-(piridin-3-il)fenil, 4-(karboksimetoksi)fenil, 4-(2-hidroksiacetamido)fenil, 4-(2-metoksiacetamido)fenil, 4-sulfamoilfenil, 4-(piperazin-1-il)fenil,4-(2-oksoimidazolidin-1-il)fenil; 4-etoksifenil, 4-(metilsulfinil)fenil,4-(2-etil-1H-imidazol-1-il)fenil, 4-(furan-2-il)fenil, 4-(metilsulfonil)fenil,4-(pirolidin-1-il)fenil, 4-(piperidin-1-il)fenil, 4-(l-metil-1H-pirazol-5-il)fenil),5-(2-metil-1H-imidazol-1-il)tiofen-2-il,4-(furan-3-il)fenil, 2-metoksipirimidin-5-il, 2-metil-4-(metilsulfonamido)fenil, 4-amino-3-klorofenil, 3,4-difluorofenil, 2,4-difluorofenil, 4-klorofenil, 4-bromotiofen-2-il, bifenil-4-il, 2-(1H-imidazol-1-il)pirimidin-5-il, 4-fluoro-3-metoksifenil, 3-cijano-4-fluorofenil, 4-karbamoil-2-metilfenil, 4-metoksi-2-metilfenil, 4-kloro-2-fluorofenil, 4-fluorofenil, 4-fluoro-2-metilfenill, 4-kloro-2-(trifluorometil)fenil,4-kloro-2-metoksifenil, 4-cijano-3-fluorofenil, 2-kloro-4-metoksifenil, 4-(1H-imidazol-1-il)tiofen-2-il, 3,5-dimetil-4-nitrofenil, 4-amino-3,5-dimetilfenil, 2-(1H-imidazol-1-il)tiazol-4-il, 2-etoksi-4-fluorofenil,4-metoksi-2-(trifluorometil)fenil, 4-fluoro-2-metoksifenil, 4-(tiazol-5-il)fenil,4-kloro- S-fluorofenil, 4-(hidroksikarbamoil)fenil, 3-fluoro-4-(1H-imidazol-1-il)fenil; 3-fluoro-4-( 2-metil- 1H-imidazol-1-il)fenil, 4-kloro-2-etoksifenil, 3-bromo-3-metoksifenil, 4-(2-ciklopropil-1H-imidazol-1-il)fenil, 4-(2-metil-1H-imidazol-1-il)tiofen-2-il, 4-bromo-2-metoksifenil,2-metoksi-4-(2-metil-1H-imidazol-1-il)fenil, 4-kloro-2-hidroksifenil, 5-bromotiofen-3-il, 4-hidroksi-3-metilfenil; 2-karbamoil-4-klorofenil, 2-acetamido -4-klorofenil, 2-metoksifenil, benzoeva kiselina, 2,4-dimetoksifenil, 4-kloro-2-propoksifenil, 4-kioro-2- (2-metoksiacetamido)fenil, 4-kloro-2-(metilsulfonamido)fenil, 4-kloro-2-(metilamino)fenil, 4-kloro-2- (metoksimetil) fenil,4-hidroksi-2-metoksi-fenil, 4-kloro-2-(dimetilamino)fenil, 4-(2-(hidroksimetil)- 1H-imidazol-1-il) fenil, 4-(2-oksooksazolidin-3-il)fenil)-1H-pirol-2-il, 4-(1H-imidazol-l-il)-2- metoksifenil, 5-(2-metil-1H-imidazol-1-il)tiofen-3-il#S-klorotiofen-2-il, 5-bromotiazol-2-ily 4-bromotiazol-2-il, 5-(2-etil-1H-imidazol-1-il)tiofen-2-il,4-kloro-2-formamidofenil, 3-klorotiofen-2-il, 4-formamido-2-metoksifenil,3-bromo-5-metoksifen-2-il, 5-(4-hidroksifenil)tiofen-2-il, 4-(tiofen-3-il)fenil, 5-(1H-imidazol-1-il)furan-2-il, 4-klorotiofen-2-il,5-bromo-4-klorotiofen-2-il, 5-(2-metil-1H-imidazol-1-il)furan-2-il, i 5-bromofuran-2-il.
6. Spoj prema zahtjevu 1 ili zahtjevu 2, ili njegova farmaceutski prihvatljiva sol, naznačen/a time, da: Ar je odabran iz skupine koju čine: 4-(1H-imidazol-1-il)fenil, 5-(1H-imidazol-1-il)tiofen-2-il, 4-(2-metil-1H-imidazol-1-il)fenil, tiazol-5-il, 4-hidroksifenil, 5-bromotiofen-2-il, 4-metoksifenil, 4-aminofenil, 4-bromofenil, 4-(furan-3-il)fenil, 3-kloro-4-metoksifenil, 3-fluoro-4-metoksifenil, 4-cijanofenil, 3-kloro-4-hidroksifenil, 4-metoksi-3-metilfenil, 4-jodofenil, 3-metoksifenil, 6-metoksipiridin-3-il, benzotdJtiazol-6-il, 4-(metiltio)fenil, 4-nitrofenil, 4-(4H-l,2,4-triazol-4-il)fenil, 4-(2H-tetrazol-5-il)fenil, benzo[d][1,3]dioksol-5-il, 6-(1H-imidazol-1-il)piridin-3-il, 5-karbamoiltiofen-2-il, 4-(1H-pirazol-4-il)fenil, 4-(trifluorometoksi)fenil, 4-karbamoilfenil, 4-(trifluorometil)fenil, 4-(1H-l,2,4-triazol-1-il)fenil;4-(1H-pirazol-1-il)fenil,4-(2-amino-2-oksoetoksi)fenil, 4-(l-metil-1H-pirazol-4-il)fenil,4-(1H-tetrazol-1-il)fenil, 4-(4-metil-1H-imidazol-1-il)fenil, 4-ureidofenil, 4-morfolinofenil, 4-(2H-tetrazol-5-il)fenil, 4-(piridin-4-il)fenil, 4-(1H-pirol-1-il)fenil, 4-(metilsulfonamido)fenil, 1H-l,2,3-triazol-1-il)fenil, naftalen-2-il, 3'-karbamoil-bifenil-4-il, 4-(6-okso-l,6-dihidropiridin-3-il)fenil, 4-(3,5-dimetilizoksazol-4-il)fenil, 4-(piridin-3-il)fenil, 4-(karboksimetoksi)fenil, 4-(2-hidroksiacetamido)fenil, 4-(2-metoksiacetamido)fenil, 4-sulfamoilfenil, 4-(piperazin-1-il)fenil, 4-(2-oksoimidazolidin-1-il)fenil, 4-etoksifenil, 4-(metilsulfinil)fenil, 4-(2-etil-1H-imidazol-1-il)fenil, 4-(furan-2-il)fenil, 4-(metilsulfonil)fenil, 4-(pirolidin-1-il)fenil, 4-(piperidin-1-il)fenil, 4-(l-metil-1H-pirazol-5-il)fenil,5-(2-metil-1H-imidazol-1-il)tiofen-2-il, 4-(furan-3-il)fenil, 2-metoksiprimidin-5-il, 2-metil-4-(metilsulfonamido)fenil, 4-amino-3-klorofenil, 3,4-difluorofenil, 2,4-difluorofenil, 4-klorofenil, 4-bromotiofen-2-il, bifenil-4-il, 2-(1H-imidazol-1-il)pirimidin-5-il, 4-fluoro-3-metoksifenil, 3-cijano-4-fluorofenil, 4-karbamoil-2-metilfenil;'l-metoksi-2-metilfenil, 4-kloro-2-fluorofenii, 4-fluorofenil, 4-fluoro-2-metilfenil, 4-kloro-2-(trifluorometil)fenil,4-kloro-2-metoksifenil, 'l-cijano-3-fluorofenil, 2- kloro-4-metoksifenil, 4-(1H-imidazol-1-il)tiofen-2-il# 3,5-dimetil-4-nitrofenil, 4-amino-3,5-dimetilfenil, 2-(1H-imidazol-1-il)tiazol-4-il, 2-etoksi-4-fluorofenil, 4-metoksi-2-(trifluorometil)fenil, 4-fluoro-2-metoksifenil, 4-(tiazol-5-il)fenil, 4-kloro-3-fluorofenil, 4-(hidroksikarbamoil)fenil, 3-fluoro-4-(1H-imidazol-1-il)fenil, 3-fluoro-4-(2-metil-1H-imidazol-1-il)fenil, 4-kloro-2-etoksifenil, 5-bromo-2-metoksifenil; 4-(2-ciklopropil-1H-imidazol-1-il)fenil, 4-(2-metil-1H-imidazol-1-il)tiofen-2-il, 4-bromo-2-metoksifenil, 2-metoksi-4-(2-metil-1H-imidazol-1-il)fenil, 4-kloro-2-hidroksifenil, 5-bromotiofen-3-il, 4-hidroksi-3-metilfenil, 2-karbamoil-4-klorofenil, 2-acetamido-4-klorofenil, 2-metoksifenil, benzoeva kiselina, 2,4-dimetoksifenil, 4-kloro-2-propoksifenil, 4-kloro-2-(2-metoksiacetamido)fenil, 4-kloro-2-(metilsulfonamido)fenil,4-kloro-2- (metilamino)fenil, 4-kloro-2-(metoksimetil)fenil, 4-hidroksi-2-metoksifenil, 4-kloro-2-(dimetilamino)fenil,4-(2-(hidroksimetil)-1H-imidazol-1-il)fenil, 4-(2-oksooksazolidin-3-il)fenil)-1H-pirol-2-il, 4-(1H-imidazol-1-il)-2-metoksifenil, 5-(2-metil-1H-imidazol-1-il)tiofen-3-il;5-klorotiofen-2-il, 5-bromotiazol-2-il, 4-bromotiazol-2-il,5-(2-etil-1H-imidazol-1-il)tiofen-2-il, 4-kloro-2-formamidofenil, 3-klorotiofen-2-il, 4-formamido-2-metoksifenil,3-bromo-5-metoksitiofen-2-il,5-(4-hidroksifenil)tiofen-2-il, 4-(tiofen-3-il)fenil, 5-(1H-imidazol-1Hl)furan-2-il, 4-klorotiofen-2-il, 5-bromo-4-klorotiofen-2-il, 5-(2-metil-1H-imidazol-1-il)furan-2-il, i 5-bromofuran-2-il.
7. Spoj prema zahtjevu 4, naznačen time, da je odabran iz sljedeće skupine: 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(5-(1H-imidazol-1-il)tiofen-2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-metil-1H-l-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(tiazol-5-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-bromotiofen-2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2,6-dimetilfenil)-5-(4-metoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-hidroksi-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-klorofenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-aminofenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromofenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(furan-3-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-4-sulfamoilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-kloro-4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-fluoro-4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-cijanofenil)-1H-pirol-2-il)propanskakiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-kloro-4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-etilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanskakiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-metoksi-3-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-jodofenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(6-metoksipiridin-3-il)-1H-pirol-2-il)propanska kiselina; 3-(5-[benzo[d]tiazol-6-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(metiltio)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-nitrofenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-amino-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(4H-l,2l4-triazol-4-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2H-tetrazol-5-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-metoksi-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(benzo[d][l;3]dioksol-5-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromofenil)-l-(4-hidroksi-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(6-(1H-imidazol-1-il)piridin-3-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(5-karbamoiltiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-pirazol-4-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(trifluorometoksi)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-karbamoilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(trifluorometil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-l,2,4-triazol-1-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-pirazol-1-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2-amino-2-oksoetoksi)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(l-metil-1H-pirazol-4-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-tetrazol-1-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(4-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-ureidofenil)-1H-pirol-2-il)propanska kiselina; 4-(2-(benzo[d][l,3]dioksol-5-il)-5-(2-karboksietil)-1H-pirol-1-il)-3-metil-benzoeva kiselina; 3-(l-(4-amino-2-metilfenil)-5-(4-bromofenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-morfolinofenil)-1H-pirol-2-il)propanska kiselina; 4-(2-(4-(2H-tetrazol-5-il)fenil)-5-(2-karboksietil)-1H-pirol-1-il)-3-metil-benzoeva kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(piridin-4-il)fenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-(1H-pirol-1-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-2,5-dimetil-fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(metil-sulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-ll2,3-triazol-1-il)fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(naftalen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3'-karbamoilbifenil-4-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(6-okso-l#6-dihidropiridin-3-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(3,5-dimetilisoksazol-4-il)feil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(piridin-3-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(karboksimetoksi)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-hidroksiacetamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-metoksiacetamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-sulfamoilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(piperazin-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-oksoimidazolidin-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-etoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(metilsulfinil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-etil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-(aminometil)-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(1H-imidazol-2-il)-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(furan-2-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(dimetilkarbamoil)-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-4-(metilkarbamoil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-metoksietilkarbamoil)-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-hidroksietilkarbamoil)-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-4-(oksazol-2-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(metilsulfonil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(2-kloro-4-hidroksifenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-2,3-dimetilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-pirolidin-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(piperidin-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(l-metil-1H-pirazol-5-il)fenil)-1H-pirol-2-il)propanska kiselina; etil-3-(5-(4-(1H-imidazol-1-il)-fenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanoat; etil-3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanoat; etil-3-(l-(4-karbamoil-2-metilfenil)-5-(5-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanoat; etil-3-(l-(4-karbamoil-2-metilfenil)-5-(4-(furan-3-il)fenil)-1H-pirol-2-il)propanoat; etil-3-(l-(4-karbamoil-2-metilfenil)-5-(4-cijanofenil)-1H-pirol-2-il)propanoat; etil-3-(l-(4-karbamoil-2-metilfenil)-5-(4-(furan-2-il)fenil)-1H-pirol-2-il)propanoat; 3-(l-(4-karbamoil-2-metilfenil)-5-(2-metoksipirimidin-5-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(2-metil-4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-acetaimdo-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-2-(trifluorometil)fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-((tetrahidrofuran-2-il)metoksi)-2-(trifluorometil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-(trifluorometil)fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(2-metil-4-propionamidofenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-(2-metoksiacetamido)-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-amino-3-klorofenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3,4-difluorofenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(2,4-difluorofenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-klorofenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromotiofen-2-il)-l-(4-karbamoil-2-metil-fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(bifenil-4-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-fluorofenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(2-(1H-imidazol-1-il)pirimidin-5-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-fluoro-3-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-cijano-4-fluorofenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-karbamoil-3-fluorofenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-metoksi-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-4-(tiazol-2-il)fenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-fluorofenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-fluorofenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-fluoro-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-(trifluorometil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-metoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-cijano-3-fluorofenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(2-kloro-4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-(dimetilamino)etilkarbamoil)-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)tiofen-2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3,5-dimetil-4-nitrofenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-amino-3,5-dimetilfenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(2-(1H-imidazol-1-il)tiazol-4-il)-l-(4-karbamoil-2-metil-fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(2-etoksi-4-fluorofenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-metoksi-2-(trifluorometil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-fluoro-2-metoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-bromofenil)-l-(2-metil-4-(piridin-3-ilkarbamoil)fenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-bromofenil)-l-(4-(6-metoksipiridin-3-ilkarbamoil)-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(6-metoksipiridin-3-ilkarbamoil)-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(tiazol-5-il)fenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-3-fluorofenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(hidroksikarbamoil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromofenil)-l-(2-metil-4-(piridin-4-ilkarbamoil)fenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-4-(piridazin-4-ilkarbamoil)fenil)-1H-pirol- 2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-4-(piridin-3-ilkarbamoil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(5-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-fluoro-4-(1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-'l-(pirimidin-5-ilkarbamoil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)fenil)-l-(2-metil-'l-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-fluoro-4-(2-metil-1H-imidazol-1-il) fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-etoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(5-bromo-2-metoksifenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-ciklopropil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromo-2-metoksifenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(2-metoksi-4-(2-metil-1H-imidazol-1-il) fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamido-2-metilfenil)-5-(4-bromofenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromofenil)-l-(4-(2-metoksiacetamido)-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5'-(4-kloro-2-hidroksifenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(5-bromotiofen-3-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-hidroksi-3-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(2-karbamoil-4-klorofenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(2-acetamido-4-klorofenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3(l-(4-karbamoil-2-metilfenil)-5-(2-metoksifenil)-1H-pirol-2-il)propanska kiselina; 4-(l-(4-karbamoil-2-metilfenil)-5-(2-karboksietil)-1H-pirol-2-il)benzoeva kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(2l4-dimetoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-propoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-('l-karbamoil-2-metilfenil)-5-(4-kloro-2-(2-metoksiacetamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-(metilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-(metoksimetil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-hidroksi-2-metoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-(dimetilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-(hidroksimetil)-1H-imidazol-1-il) fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-(2-oksooksazolidin-3-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)-2-metoksifenil)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(5-(2-metil-1H-imidazol-1-il)tiofen-3-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(5-klorotiofen-2-il)-1H-pirol-2-il) propanska kiselina; 3-(5-(5-bromotiazol-2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-l-(2-metil-4-(metilsulfonamido) fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-(2-metil-1H-imidazol-1-il)tiofen-2-il)-l-(2-metil-4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamido-2-metilfenil)-5-(4-kloro-2-metoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-bromotiazol-2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(5-bromotiofen-2-il)-l-(2-metil-'l-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamido-2-metilfenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-kloro-2-metoksifenil)-l-(2-metil-4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(5-(2-etil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-kloro-2-formamidofenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(3-klorotiofen-2-il)-1H-pirol-2-il) propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-formamido-2-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(3-bromo-5-metoksitiofen-2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(5-(4-hidroksifenil)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromotiofen-2-il)-l-(2-metil-4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 2-(l-(4-karbamoil-2-metilfenil)-5-(4-(tiofen-3-il)fenil)-1H-pirol-2-il)octena kiselina; 3-(5-(4-bromofenil)-l-(2-metil-4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-(1H-imidazol-1-il)furan2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-kloro-2-metoksifenil)-l-(2-metil-4-sulfamoilfenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(4-klorotiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-bromo-4-klorotiofen-2-il)-l-(4-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-bromotiofen-2-il)-l-(2-metil-'l-sulfamoilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksi-fenil)-l-(2-metil-(piridin-4-ilkarbamoil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-2-metilfenil)-5-(5-(2-metil-1H-imidazol-1-il)furan-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-bromofuran-2-il)-l-('l-karbamoil-2-metilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-(2-metil-1H-imidazol-1-il)tiofen-2-il)-l-(2-metil-4-sulfamoilfenil)-1H-pirol-2-il)propanska kiselina; 3-(5-('l-bromofenil)-l-(2-metil-4-(sulfamoilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-metil-4-(sulfamoilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-kloro-2-metoksifenil)-l-(2-metil-4-(sulfamoilamino)fenil)-1H-pirol-2-il)propanska kiselina; i 3-(l-(4-karbamoil-2-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)butanska kiselina; ili njihova farmaceutski prihvatljiva sol.
8. Farmaceutski sastavi, naznačeni time, da obuhvaćaju terapeutski učinkovitu količinu spoja prema zahtjevu 1, ili njegove farmaceutski prihvatljive soli, zajedno s farmaceutski prikladnim nosačem ili pomoćnim sredstvima.
9. Spoj formule I ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 7, naznačen,a time, da se upotrebljava u postupku liječenja.
10. Spoj formule I ili njegova farmaceutski prihvatljiva sol, prema bilo kojem od zahtjeva 1 do 7, naznačen,a time, da se upotrebljava u postupku liječenja poremećaja odabranih od sljedećih: plućni poremećaji povezani s hipoksemijom i,ili sa stezanjem glatkih mišića u plućima i,ili s plućnim infekcijama i,ili s plućnim ozljedama, kardiovaskularna bolest i srčana bolest, uključujući stanja kao što su hipertenzija, ishemijski koronarni sindromi, ateroskleroza, zastoj srca, glaukom, bolesti koje su karakerizirane angiogenezom, poremećaji kod kojih se pojavljuje rizik od tromboze, poremećaji kod kojih se pojavljuje rizik od restenoze, kronične upalne bolesti, poremećaji kod kojih se pojavljuje rizik od apoptoze, impotencija, pretilost uzrokovana prekomjernim jelom kao odgovorom na žudnju za hranom, moždani udar, reperfuzijska ozljeda, i poremećaji kod kojih je povoljno rekondicioniranje srca ili mozga za NO-zaštitu protiv naknadnih ishemijskih događaja.
11. Spoj, naznačen time, da ima sljedeću formulu II, ili njegova farmaceutski prihvatljiva sol: [image] u kojoj Ar je odabran iz skupine koju čine: aril, supstituirani aril, heteroaril i supstituirani heteroaril, pri čemu je aril 5-člani do 14-člani monociklički, biciklički ili triciklički aromatski sustav prstena; i heteroaril je aromatski heterociklički prsten od 5 do 14 članova, koji ima najmanje jedan heteroatom odabran od dušika, kisika i sumpora, te sadrži najmanje jedan ugljikov atom, uključujući monocikličke, bicikličke i tricikličke sustave prstena, gdje su supstituenti za aril i heteroaril, odabrani iz skupine koju čine: -halo, -ORe', -OC(O)Re'-NRe'Re", -SRe', -Re', -CN, -NO2, -C(O)2ReRe", -C(O)Re', -OC(O)NReRe", -NRe"c(O)Re', -NRe"C02Re', -NRe"C(O)NRe'Re", -NRe"sO2NReRel, -NHC(NH2)=NH, -NReC(NH2)=NH, NH-C(NH2)=NRe', -S(O)Re', -SO2Re', -SO2NRe'Re', -NRe"SO2Re', -N3, -CH(Ph)2, perfluoroalkoksi i perfluoro(C1-C4)alkil, u količini koja ide u rasponu od nula do ukupnog broja otvorenih valencija na aromatskom sustavu prstena; i pri čemu su Re, Re i Re neovisno odabrani od sljedećih: vodik, nesupstituirani (C1-C4)alkil, nesupstituirani hetero(C1-C8)alkil, nesupstituirani aril, nesupstituirani heteroaril, nesupstituirani aril(C1-C4)alkil, nesupstituirani ariloksi(C1-C4)alkil, monosupstituirani aril i monosupstituirani heteroaril; R1 je odabran iz skupine koju čine: vodik, C1-C6 alkiiy C3-C6 cikloalkil, aril, supstituirani aril, heteroaril i supstituirani heteroaril, gdje su aril, heteroaril i supstituenti za aril i heteroaril prethodno definirani; X1 do X4 su neovisno odabrani iz skupine koju čine C i N; R5 je odabran iz skupine koju čine: vodik, hidroksil, halogen, C1-C6 alkil, C3-C6cikloalkil, cijano, nitro, karbamoil, C1-C6alkilkarbamoil, karboksil, C1-C6 alkilhidroksi, sulfamoil, C1-C6alkilsulfamoil, amino, C1-C6alkilamino, C1-C6dialkilamino, C1-C5alkoksil i C3-C6cikloalkoksil; R6 je odabran iz skupine koju čine: halogen, hidroksil, karbamoil, supstituirani karbamoil, C1-C6alkilkarbamoil, sulfamoil, C1-C6alkilsuIfamoil, C1-C6alkil, C3-C6cikloaikit, cijano, nitro, amino, CF3, karboksil, ureido, sulfamoilamino, 2-amino-2-oksoetil, C1-C6alkilamino, C1-C6dialkiiamino, arilamino, heteroarilamino, C1-C6alkoksi, C3-C6cikloalkoksil, 1H-imidazoi-2-il i 2-metil-1H-imidazol-1-il; ili alternativno R5 i R6 zajedno tvore supstituirani ili nesupstituirani 5-člani ili 6-člani heterociklički prsten koji sadrži najviše 2 heteroatoma odabrana od O, N ili S; R7 je odabran iz skupine koju čine: vodik, hidroksil, halogen, C1-C6alkil, C3-C6cikloalkil, cijano, nitro, karbamoil, C1-C6alkilkarbamoil, sulfamoil, C1-C6alkilsulfamoily amino, C1-C6alkilamino, C1-C6dialkilamino, C1-C6alkoksi i C1-C6,cikloalkoksil; n je 0-3; gdje R5 može biti vodik samo onda, kada najmanje jedan od X: do X4 je N; te dodatno s time da X1 i X3 moraju biti CH ili N, osim ako R5 i R5 zajedno tvore 5-člani ili 6-člani heterociklički prsten ili najmanje jedan od X1 do X4je N; i pri čemu Ar isključuje supstituirani ili nesupstituirani indazol-3-il i supstituirani ili nesupstituirani 1H-pirazolo[3,4-b]piridil; sa sljedećim uvjetima: uvjet IIa: kada su svi X jednaki C, a jedan od R5, R6ili R7je karboksil, metilsulfonamido, ili sulfamoil, tada Ar ne može biti fenil; ni supstituirani ili nesupstituirani fenil-(C1-C3)-alkil, niti fenil-(C2-C5)-alkenii; i uvjet IIb: kada su svi X jednaki C i jedan od R5, R6 i R7 je neovisno odabran iz skupine koju čine halogen i metil, tada Ar ne može biti 4-hidroksifenil, ni 4- C1-C6-aciloksifenil; i uvjet IIc: kada su svi X jednaki C i R5 je metil, Cl, hidroksil, trifluorometil i R6je metil, metoksi, karboksietil, Cl ili karboksipropil, a n je 1, tada Ar ne može biti fenil, 4-metil-fenil, 4-metoksi-fenil, 4-halofenil, ni tiofen-il; i uvjet IId: kada su svi X jednaki C i R5 i R6 zajedno tvore heterociklički prsten a rezultirajući biciklički sustav prstena je benzo[d]tiazol supstituiran na poziciji 2 s C1-C3-alkilom, tada Ar ne može biti fenil, 4-F-fenil, 4-metoksi-fenil, ni tiofen-il.
12. Spoj prema zahtjevu 11, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da Ar je odabran iz skupine koju čine: fenil, supstituirani fenil, tiofen-il, supstituirani tiofen-il, piridinil, supstituirani piridinil, tiazolil i supstituirani tiazolil.
13. Spoj prema zahtjevu 11, naznačen time, da je odabran iz sljedeće skupine: 3-(5-(4-metoksifenil)-l-(l-oksoizoindolin-5-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-3-metoksi-fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(1H-benzo[d]imidazol-6-il)-5-(4-metoksi-fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-3-hidroksifenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(5-karbamoilpiridin-2-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(3-kloro-4-hidroksifenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(6-karbamoilpiridin-3-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(l-okso-l,3-dihidroizobenzofuran-5-il)-1H-pirol-2-il)propanska kiselina; 3-(l-(1H-benzo[d]imidazol-6-il)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(l,3-dioksoizoindolin-5-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(1H-indazol-5-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(6-okso-l,6-d ih idropirid i n-3-il)-1H-pirol-2-il) propanska kiselina; 3-(l-(2-aminobenzo[d]tiazol-6-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-3-metilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(1H-indazol-6-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(2-okso-2,3-dihidro-1H-benzo[d]imidazol-5-il)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(2-okso-2,3-dihidro-1H-benzo[cl]imidazol-5-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(kinolin-6-il)-1H-pirol)-2-il)propanska kiselina; 3-(l-(4-hidroksi-3,5-dimetilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(5-(1H-imidazol-1-il)piridin-2-il)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(5-metil-1H-benzo[d]imidazol-6-il)-1H-pirol-2-il)propanska kiselina; 3-{l-(3-kloro-4-cijanofenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoil-3-klorofenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(izokinolin-6-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(izokinolin-7-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(1H-indol-5-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(2-oksoindolin-5-il)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(3-cijano-4-fluorofenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-{l-(4-hidroksf-3-(metoksikarbonil)fenil)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-3-(metoksikarbonil)fenil)-5-(4-metoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(l-(3-fluoro-4-hidroksifenil)-3-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-3-(hidroksimetil)fenil)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(3-aminobenzo[d]izoksazol-6-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 5-(2-(2-karboksietil)-5-fenil-1H-pirol-1-il)-2-hidroksi-benzoeva kiselina; 3-(l-(3-aminobenzo[d]izoksazol-5-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksi-3-(hidroksimetil)fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)fenil)-l-(2-okso-2,3-dihidrobenzo[d]oksazol-5-il)-1H-pirol-2-il)propanska kiselina; i 3-(5-(4-(2-metil-1H-imdazol-1-il)fenil)-l-(2-okso-2,3-dihidrobenzo[d]oksazol-6-il)-1H-pirol-2-il)propanska kiselina; ili njihova farmaceutski prihvatljiva sol.
14. Farmaceutski sastav, naznačen time, da obuhvaća terapeutski učinkovitu količinu spoja prema zahtjevu 11, zajedno s farmaceutski prikladnim nosačem ili pomoćnim sredstvom.
15. Spoj formule II ili njegova farmaceutski prihvatljiva sol prema zahtjevu 11, naznačen/a time, da se upotrebljava u postupku liječenja.
16. Postupak priprave farmaceutskog sastava prema zahtjevu 14, naznačen time, da postupak obuhvaća korak sastavljanja spoja formule II prema zahtjevu 11, ili njegove farmaceutski prihvatljive soli, s farmaceutski prikladnim nosačem ili pomoćnim sredstvom.
17. Spoj, naznačen time, da ima sljedeću formulu III, ili njegova farmaceutski prihvatljiva sol: [image] u kojoj Ar je odabran iz skupine koju čine: aril, supstituirani aril, heteroaril i supstituirani heteroaril, pri čemu je aril 5-člani do 14-člani monociklički, biciklički ili triciklički aromatski sustav prstena; i heteroaril je aromatski heterociklički prsten od 5 do 14 članova, koji ima najmanje jedan heteroatom odabran od dušika, kisika i sumpora, te sadrži najmanje jedan ugljikov atom, uključujući monocikličke, bicikličke i tricikličke sustave prstena, gdje su supstituenti za aril i heteroaril, odabrani iz skupine koju čine: -halo, -ORe',-OC(O)Re'-NRe'Re", -SRe', -Re', -CN, -NO2, -CO2Re', -C(O)NRe'Re", -C(O)Rel, -OC(O)NRe'Re", -NRe"c(O)Re', -NRe"CO2Re', -NRe"C(O)NRe'Re", -NRe"'SO2NRe'Re", -NHC(NH2) = NH, -NReC(NH2)=NH, NH-C(NH2) = NRe', -S(O)Re', -SO2Re', -SO2NReRe", -NRe"S02Re', -N3, -CH(Ph)2, perfluoroalkoksi i perfluoro(C1-C4)alkil, u količini koja ide u rasponu od nula do ukupnog broja otvorenih valencija na aromatskom sustavu prstena; i pri čemu su Re, Re i Re neovisno odabrani od sljedećih: vodik, nesupstituirani (C1-C8)alkil, nesupstituirani hetero(C1-C8)alkil,nesupstituirani aril, nesupstituirani heteroaril, nesupstituirani aril(C1-C4)alkil, nesupstituirani ariloksi(C1-C4)alkil; monosupstituirani aril i monosupstituirani heteroaril; R1 je odabran iz skupine koju čine: vodik, C1-C6alkil, C3-C6cikloalkil, aril, supstituirani aril, heteroaril i supstituirani heteroaril, gdje su aril, heteroaril i supstituenti za aril i heteroaril prethodno definirani; X5 do X8 su neovisno odabrani iz skupine koju čine N, C i S, pri čemu najmanje jedan X mora biti N ili S; R8 i R9 su neovisno odabrani iz skupine koju čine: vodik, halogen, hidroksil, karbamoil, supstituirani karbamoil, sulfamoil, supstituirani sulfamoil, C1-C6alkil, C3-C6cikloalkil, cijano, nitro, amino, CF3, karboksil, ureido, sulfamoilamino, 2-amino-2-oksoetil, C1-C6alkilamino, C1-C6dialkilamino, arilamino, heteroarilamino, C1-C6alkoksil, C3-C6cikloalkoksil, aril, ariloksil, spstituirani aril, heteroaril, supstituirani heteroaril i ništa ako su svi od X5 do X8jednaki N, dok su aril, heteroaril i supstituenti za aril i heteroaril prethodno definirani; n je 0-3; i pri čemu Ar isključuje supstituirani ili nesupstituirani indazol-3-il i supstituirani ili nesupstituirani 1H-pirazolo[3,4-b]piridil.
18. Spoj prema zahtjevu 17, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da Ar je odabran iz skupine koju čine: fenil, supstituirani fenil, tiofen-il, supstituirani tiofen-il, piridinil, supstituirani piridinil, tiazolil, supstituirani tiazolil, biciklički aril, supstituirani biciklički aril, biciklički heteroaril i supstituirani biciklički heteroaril.
19. Spoj prema zahtjevu 17, naznačen time, da je odabran iz sljedeće skupine: 3-(1-(5-karbamoiltiofen-2-il)-5-(4-metoksifenil)-1H-pirol-2-propanska kiselina; 3-(1-(5-karbamoiltiazol-2-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(1-(4-karbamoiltiofen-2-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(1-(5-karbamoiltiofen-3-il)-5-(4-metoksifenil)-1H-pirol-2-il) propanska kiselina; 3-(1-(4-(2-amino-2-oksoetil)tiazol-2-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; i 3-(1-(4-karbamoiltiazol-2-il)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; ili njihova farmaceutskiprihvatljiva sol.
20. Farmaceutski sastav, naznačen time, da obuhvaća terapeutski učinkovitu količinu spoja prema zahtjevu 17, zajedno s farmaceutski prikladnim nosačem ili pomoćnim sredstvom.
21. Spoj formule III ili njegova farmaceutski prihvatljiva sol prema zahtjevu 17, naznačen,a time, da se upotrebljava u postupku liječenja.
22. Postupak priprave farmaceutskog sastava prema zahtjevu 20, naznačen time, da postupak obuhvaća korak sastavljanja spoja formule III prema zahtjevu 17, ili njegove farmaceutski prihvatljive soli, s farmaceutski prikladnim nosačem ili pomoćnim sredstvom.
23. Spoj, naznačen time, da ima sljedeću formulu IV ili njegova farmaceutski prihvatljiva sol, koji,koja se upotrebljava u postupku liječenja poremećaja odabranog između sljedećih: plućni poremećaji povezani s hipoksemijom i,ili sa stezanjem glatkih mišića u plućima i,ili s plućnom infekcijom i,ili s ozljedom pluća, kardiovaskularna bolest i srčana bolest, uključujući stanja kao hipertenzija, ishemijski koronarni sindromi, ateroskleroza, zastoj srca, glaukom, bolesti koje su karakterizirane angiogenezom, poremećaji gdje postoji rizik od pojave tromboze, poremećaji gdje postoji rizik od pojave restenoze, bolesti kod kojih postoji rizik od pojave apoptoze, impotencija, pretilost uzrokovana prekomjernim jelom kao odgovorom na žudnju za hranom, moždani udar, reperfuzijska ozljeda, i poremećaji kod kojih je povoljno rekondicioniranje srca ili mozga za NO-zaštitu protiv naknadnih ishemijskih događaja; pri čemu postupak obuhvaća inhibiranje GSNOR kod pojedinca kojemu je to potrebno: [image] u kojoj Ar je odabran iz skupine koju čine: aril, supstituirani aril, heteroaril i supstituirani heteroaril, pri čemu je aril 5-člani do 14-člani monociklički, biciklički ili triciklički aromatski sustav prstena; i heteroaril je aromatski heterociklički prsten od 5 do 14 članova, koji ima najmanje jedan heteroatom odabran od dušika, kisika i sumpora, te sadrži najmanje jedan ugljikov atom, uključujući monocikličke, bicikličkei tricikličke sustave prstena, gdje su supstituenti za aril i heteroaril, odabrani iz skupine koju čine: -halo,-ORe',-OC(O)Re'-NReRe",-SRe', -Re', -CN,-NO2,-CO2Re', -C(O)NReRe", -C(O)Re', -OC(O)NReRe", -NRe"c(O)Re', -NRe"CO2Re', -NRe"c(O)NReRe", -NRe"SO2NRe'Re", -NHC(NH2)=NH, -NReC(NH2)=NH, NH-C(NH2)=NRe', -S(O)Re', -SO2Re', -SO2NRe'Re", -NRe"sO2Re', -N3, -CH(Ph)2, perfluoroalkoksi i perfluoro(C1-C4)alkil, u količini koja ide u rasponu od nula do ukupnog broja otvorenih valencija na aromatskom sustavu prstena; i pri čemu su Re, Re i Re neovisno odabrani od sljedećih: vodik, nesupstituirani (C1-C8)alkil, nesupstituirani hetero(C1-C8)alkil, nesupstituirani aril, nesupstituirani heteroaril, nesupstituirani aril(C1-C4)alkil, nesupstituirani ariloksi(C1-C4)alkil, monosupstituirani aril i monosupstituirani heteroaril; R1 je odabran iz skupine koju čine: vodik, C1-C6alkil, C3-C6cikloalkil, aril, supstituirani aril, heteroaril i supstituirani heteroaril, gdje su aril, heteroaril i supstituenti za aril i heteroaril prethodno definirani; R10je hidroksil, karbamoil, ureido, sulfamoilamino, 2-amino-2-oksoetil, acetil, hidroksietil, piridin-3-ilamino, piridin-4-ilamino, l-metilpirolidin-3-iloksi, trifluoroacetil, imidazol-1-il, acetamido, metilsulfamido, 2-oksooksazolidin-3-il, 2-hidroksietilamino i metilkarbamoil; n je 0-3; pri čemu Ar isključuje supstituirani ili nesupstituirani indazol-3-il i supstituirani ili nesupstituirani 1H-pirazolo[3,4-b]piridil; uz sljedeći uvjet: uvjet IVa: kada Rio je hidroksil ili karbamoil, tada Ar ne može biti fenil, 4-metil-fenil, 4-metoksi-fenil, 4-halo-fenil niti tiofen-il, kada n je 0 ili 1.
24. Spoj za uporabu prema zahtjevu 23, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da Ar je odabran iz skupine koju čine: fenil, supstituirani fenil, tiofen-il, supstituirani tiofen-il, piridinil, supstituirani piridinil, tiazolil i supstituirani tiazolil.
25. Spoj za uporabu prema zahtjevu 23, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da Ar je odabran iz skupine koju čine: fenil, 3-metoksifenil, 4-metoksifenil, 4-kloro-2-metoksifenil, 2-metoksi-4- (2-metil-1H-imidazol-1-il)fenil, 1H-imidazol-1-il-fenil, 2-metil-1H-imidazol-1-il-fenil, 1H-imidazol-1-il-tiofen-2-il i 2-metil-1H-il-imidazol-1-il-tiofen-2-il.
26. Spoj za uporabu prema zahtjevu 23, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da je odabran,a iz sljedeće skupine: 3-(l-(4-karbamoilfenil)-5-(3-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-fenil-l-(4-ureidofenil)-1H-pirol-2-il)propanska kiselina; 3-(5-fenil-l-(4-(sulfamoilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-amino-2-oksoetil)fenil)-5-fenil-1H-pirol-2-il) propanska kiselina; 3-(l-(4-(2-amino-2-oksoetil)fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(metilkarbamoil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksifenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 2-(l-(4-hidroksifenil)-5-(4-metoksifenil-1H-pirol-2-il)octena kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-(1H-imidazol-1-il)tiofen-2-il)-l-(4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetilfenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(l-hidroksietil)fenil)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksifenil)-5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(piridin-3-ilamino)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(l-metilpirolidin-3-iloksi)fenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(piridin-4-ilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-fenil-l-(4-(2,2,2-trifluoroacetil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(2,2,2-trifluoroacetil)fenil)-1H-piroI-2-il)propanska kiselina; 3-(l-(4-(1H-imidazol-1-il)fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-kloro-2-metoksifenil)-l-(4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamidofenil)-5-(4-kloro-2-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamilfenil)-5-(4-kloro-2-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-kloro-2-metoksifenil)-l-(4-(metilsulfonamido)fenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)fenil)-l-(4-(2-oksooksazolidin-3-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-l-(4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamidofenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il) propanska kiselina; 3-(5-(2-metoksi-4-(2-metil-1H-imidazol-1-il)fenil)-l-(4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamidofenil)-5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il) propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)fenil)-l-(4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-hidroksietilamino)fenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; i 3-(l-(4-hidroksifenil)-5-(5-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il) propanska kiselina.
27. Spoj, naznačen time, da je odabran iz sljedeće skupine: 3-(1-(4-karbamoilfenil)-5-(3-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-fenil-l-(4-ureidofenil)-1H-pirol-2-il)propanska kiselina; 3-(5-fenil-l-(4-(sulfamoilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-amino-2-oksoetil)fenil)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-amino-l-oksoetil)fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksi-fenil)-l-(4-(metilkarbamoil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksifenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 2-(l-(4-hidroksifenil)-5-(4-metoksifenil)-1H-pirol-2-il)octena kiselina; 3-(5-(4-(1H-imidazol-1-il)fenil)-l-(4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(5-(1H-imidazol-1-il)tiofen-2-il)-l-(4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(l-hidroksietil)fenil)-5-fenil-1H-pirol-2-il)propanska kiselina; 3-(l-(4-hidroksifenil)-5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(piridin-3-ilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(l-metilpirolidin-3-iloksi)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenii)-l-(4-(piridin-4-ilamino)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-fenil-l-(4-(2,2,2-trifluoroacetil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-metoksifenil)-l-(4-(2,2,2-trifluoroacetil)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(1H-imidazol-1-il)fenil)-5-(4-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-kloro-2-metoksifenil)-l-(4-hidroksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamidofenil)-5-(4-kloro-2-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-karbamoilfenil)-5-(4-kloro-2-metoksifenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-kloro-2-metoksifenil)-l-(4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)fenil)-l-(4-(2-oksooksazolidin-3-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-l-(4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamidofenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; 3-(5-(2-metoksi-4-(2-metil-1H-imidazol-1-il)fenil)-l-(4-(metilsulfonamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-acetamidofenil)-5-(4-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; 3-(5-(4-(2-metil-1H-imidazol-1-il)fenil)-l-(4-(metilsulfoniamido)fenil)-1H-pirol-2-il)propanska kiselina; 3-(l-(4-(2-hidroksietilamino)fenil)-5-(4-(2-metil-1H-imidazol-1-il)fenil)-1H-pirol-2-il)propanska kiselina; i 3-(l-(4-hidroksifenil)-5-(5-(2-metil-1H-imidazol-1-il)tiofen-2-il)-1H-pirol-2-il)propanska kiselina; ili njihova farmaceutski prihvatljiva sol.
28. Farmaceutski sastav, naznačen time, da obuhvaća terapeutski učinkovitu količinu spoja prema zahtjevu 27, zajedno s farmaceutski prikladnim nosačem ili pomoćnim sredstvom.
29. Spoj prema zahtjevu 27, ili njegova farmaceutski prihvatljiva sol, naznačen,a time, da se upotrebljava u postupku liječenja.
30. Postupak priprave farmaceutskog sastava prema zahtjevu 28, naznačen time, da postupak obuhvaća korak sastavljanja spoja prema zahtjevu 27, ili njegove farmaceutski prihvatljive soli, s farmaceutski prikladnim nosačem ili pomoćnim sredstvom.
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Families Citing this family (38)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8455513B2 (en) 2007-01-10 2013-06-04 Aerie Pharmaceuticals, Inc. 6-aminoisoquinoline compounds
US8450344B2 (en) 2008-07-25 2013-05-28 Aerie Pharmaceuticals, Inc. Beta- and gamma-amino-isoquinoline amide compounds and substituted benzamide compounds
DK2315590T3 (da) * 2008-08-15 2012-11-19 N30 Pharmaceuticals Inc Pyrrolinhibitorer af S-nitrosoglutathionreduktase
US8470857B2 (en) 2008-08-15 2013-06-25 N30 Pharmaceuticals, Inc. Pyrrole inhibitors of S-nitrosoglutathione reductase as therapeutic agents
ES2572615T3 (es) 2008-08-15 2016-06-01 Nivalis Therapeutics, Inc. Nuevos inhibidores pirrólicos de S-nitrosoglutatión reductasa como agentes terapéuticos
EP3828172A1 (en) 2009-05-01 2021-06-02 Aerie Pharmaceuticals, Inc. Dual mechanism inhibitors for the treatment of disease
US8586624B2 (en) * 2009-12-16 2013-11-19 N30 Pharmaceuticals, Inc. Thiophene inhibitors of S-nitrosoglutathione reductase
ES2550939T3 (es) 2010-07-16 2015-11-13 Nivalis Therapeutics, Inc. Nuevos compuestos de dihidropiridin-2-(1H)-ona como inhibidores de la S-nitrosoglutatión reductasa y antagonistas del receptor de la neurocinina-3
US8906933B2 (en) 2010-09-24 2014-12-09 N30 Pharmaceuticals, Inc. Dihydropyrimidin-2(1H)-one compounds as neurokinin-3 receptor antagonists
DK2624695T3 (en) 2010-10-08 2016-01-04 Nivalis Therapeutics Inc NOVEL SUBSTITUTED quinoline-RELATIONS AS S-NITROSOGLUTATHIONREDUKTASEINHIBITORER
AU2011343518B2 (en) * 2010-12-16 2016-11-10 Nivalis Therapeutics, Inc. Novel substituted bicyclic aromatic compounds as S-nitrosoglutathione reductase inhibitors
US20140135396A1 (en) * 2011-07-05 2014-05-15 Beth Israel Deaconess Medical Center, Inc. Treatment of Acetaminophen-Induced Liver Damage by the Administration of Modulators of Nitric Oxide
WO2013006635A1 (en) * 2011-07-05 2013-01-10 N30 Pharmaceuticals, Llc Novel pyrrole inhibitors of s-nitrosoglutathione reductase as therapeutic agents for liver toxicity
WO2013138617A1 (en) 2012-03-16 2013-09-19 Axikin Pharmaceuticals, Inc. 3,5-diaminopyrazole kinase inhibitors
ES2852377T3 (es) 2013-03-15 2021-09-13 Aerie Pharmaceuticals Inc Sales dimesilato de 4-(3-amino-1-(isoquinolin-6-ilamino)-1-oxopropan-2-il)bencilo, sus combinaciones con prostaglandinas y el uso de las mismas en el tratamiento de trastornos oculares
NZ631142A (en) 2013-09-18 2016-03-31 Axikin Pharmaceuticals Inc Pharmaceutically acceptable salts of 3,5-diaminopyrazole kinase inhibitors
CN105980381A (zh) 2013-11-08 2016-09-28 拜耳医药股份有限公司 取代的尿嘧啶及其用途
EP3066096A1 (de) 2013-11-08 2016-09-14 Bayer Pharma Aktiengesellschaft Substituierte uracile als chymase inhibitoren
JP6364967B2 (ja) * 2014-05-30 2018-08-01 東ソー株式会社 ジチエノベンゾジチオフェンの製造方法
TWI703133B (zh) 2014-12-23 2020-09-01 美商艾克斯基製藥公司 ３,５-二胺基吡唑激酶抑制劑
CN104529995B (zh) * 2014-12-30 2016-04-27 白银摩尔化工有限责任公司 一种空气或纯氧催化氧化溴化氢制备2,3,5-三溴噻吩的方法
CN104557656B (zh) * 2015-01-13 2016-06-01 佛山市赛维斯医药科技有限公司 含卤苯和二烯金刚烷结构的化合物、其制备方法和用途
WO2017044766A1 (en) 2015-09-10 2017-03-16 Nivalis Therapeutics, Inc. Solid forms of an s-nitrosoglutathione reductase inhibitor
CN105218397B (zh) * 2015-09-25 2017-05-10 济南大学 2‑叠氮甲基‑4‑硝基苯甲酰氯的合成方法
EP3404021A4 (en) 2016-01-12 2019-09-11 Nippon Chemiphar Co., Ltd. VOLTAGE-RELATED T-TYPE CALCIUM CHANNEL INHIBITOR
US10537557B2 (en) * 2016-01-27 2020-01-21 Case Western Reserve University Methods of treating respiratory disorders
EP3795563B1 (en) 2016-03-31 2024-07-17 Oncternal Therapeutics, Inc. Indoline analogs and uses thereof
TW201806596A (zh) * 2016-08-01 2018-03-01 中央研究院 抗病毒劑
KR102568079B1 (ko) 2016-08-31 2023-08-17 에어리 파마슈티컬즈, 인코포레이티드 안과용 조성물
US9840468B1 (en) 2016-12-30 2017-12-12 Aerie Pharmaceuticals, Inc. Methods for the preparation of 6-aminoisoquinoline
AU2018243687C1 (en) 2017-03-31 2020-12-24 Alcon Inc. Aryl cyclopropyl-amino-isoquinolinyl amide compounds
JP2020100564A (ja) * 2017-04-03 2020-07-02 京都薬品工業株式会社 リードスルー誘導剤およびその医薬用途
US11655244B2 (en) * 2017-04-11 2023-05-23 Gsno Therapeutics, Inc. Carbazole compounds and methods of use thereof
WO2018208793A1 (en) 2017-05-08 2018-11-15 Musc Foundation For Research Development S-nitrosoglutathiome (gsno) and gsno reductase inhibitors for use in therapy
CA3112391A1 (en) 2018-09-14 2020-03-19 Aerie Pharmaceuticals, Inc. Aryl cyclopropyl-amino-isoquinolinyl amide compounds
CN110015963A (zh) * 2019-04-12 2019-07-16 上海优合生物科技有限公司 一种2-氯-6-甲基苯胺的制备方法
WO2021026429A1 (en) * 2019-08-08 2021-02-11 Treventis Corporation Butyrylcholinesterase compounds and use in diseases of the nervous system
CN112574193B (zh) 2020-12-31 2022-05-17 南京医科大学 一类口服gsnor抑制剂及其药物用途

Family Cites Families (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3168528A (en) 1962-06-14 1965-02-02 Parke Davis & Co 1-(p-nitrophenyl) and 1-(p-cyanophenyl)-5-arylpyrrole-2-propionic acid compounds
GB997043A (en) 1962-06-14 1965-06-30 Parke Davis & Co Derivatives of 1,5-diarylpyrrole-2-propionic acid
US3168529A (en) * 1962-06-14 1965-02-02 Parke Davis & Co 1-(p-lower alkanoylphenyl)-5-arylpyrrole-2-propionic acid compounds
US3168527A (en) 1962-06-14 1965-02-02 Parke Davis & Co 1-aryl-5-(p-fluorophenyl)-pyrrole-2-propionic acid compounds
US3168532A (en) * 1963-06-12 1965-02-02 Parke Davis & Co 1, 5-diarylpyrrole-2-propionic acid compounds
US3168531A (en) * 1963-06-12 1965-02-02 Parke Davis & Co 1-aryl-5-(p-lower alkoxyphenyl)-pyrrole-2-propionic acid compounds
FR1393615A (fr) 1964-03-05 1965-03-26 Inst Organiycheskoi Khim Im N Procédé de préparation de la nu-vinylpyrrolidone
US3427305A (en) * 1966-11-01 1969-02-11 Searle & Co 5 - ((halo/alkoxy)phenyl) - 1 - (p - sulfonamido(phenyl/benzyl)) - 2 - pyrrolepropionic acids
US3752826A (en) * 1970-01-26 1973-08-14 Mcneilab Inc Aroyl substituted pyrroles
US4522811A (en) 1982-07-08 1985-06-11 Syntex (U.S.A.) Inc. Serial injection of muramyldipeptides and liposomes enhances the anti-infective activity of muramyldipeptides
US4694018A (en) * 1985-11-29 1987-09-15 G. D. Serale & Co. Substituted 1,5-diphenyl-2-pyrrolepropionic acids and derivatives
US4792568A (en) * 1986-04-14 1988-12-20 Rorer Pharmaceutical Corporation Aryl pyrroles as useful antiallergy compounds
US4826869A (en) 1988-02-19 1989-05-02 Syntex (U.S.A.) Inc. N-(lower alkyl)-2-(3'ureidobenzyl)pyrrolidines
US5189051A (en) 1990-05-10 1993-02-23 E. I. Du Pont De Nemours And Company Treatment of glaucoma and ocular hypertension with pyrrole angiotensin-II receptor antagonists
DE4036706A1 (de) 1990-11-17 1992-05-21 Hoechst Ag Verfahren zur behandlung der cardialen sowie der vasculaeren hypertrophie und hyperplasie
US5187271A (en) 1991-02-28 1993-02-16 G. D. Searle & Co. N-substituted (α-imidazolyl-toluyl) pyrrole compounds for treatment of circulatory disorders
US6008368A (en) 1993-04-28 1999-12-28 G. D. Searle & Co. Pharmaceutical compositions for treatment of circulatory disorders using N-substituted (α-imidazolyl-toluyl) pyrrole aniotensin II antagonists
US5451597A (en) 1993-05-27 1995-09-19 G.D. Searle & Co. Treatment of circulatory disorders using n-substituted (α-imidazolyl-toluyl) pyrrole angiotensin II antagonists
US5840751A (en) 1993-11-19 1998-11-24 Warner-Lambert Company 5,6-dihydropyrone derivatives as protease inhibitors and antiviral agents
US6057367A (en) 1996-08-30 2000-05-02 Duke University Manipulating nitrosative stress to kill pathologic microbes, pathologic helminths and pathologically proliferating cells or to upregulate nitrosative stress defenses
ATE336240T1 (de) * 1996-11-13 2006-09-15 Cold Spring Harbor Lab Therapeutische verwendung von stickstoffmonoxydinhibitoren
PT946507E (pt) * 1996-12-10 2004-02-27 Searle & Co Compostos de pirrolilo substituidos para o tratamento da inflamacao
FR2782720B1 (fr) * 1998-09-01 2001-10-12 Oreal Utilisation en teinture capillaire de condensats de quinoline-5,8-diones ou de quinoxaline-5,8-diones et de pyrroles, anilines ou indoles substitues
US6355812B1 (en) * 1999-06-11 2002-03-12 Orth-Mcneil Pharmaceutical, Inc. Methods for the synthesis of dioxoalkanoic acid compounds
US6589978B2 (en) * 2000-06-30 2003-07-08 Hoffman-La Roche Inc. 1-sulfonyl pyrrolidine derivatives
US7049308B2 (en) * 2000-10-26 2006-05-23 Duke University C-nitroso compounds and use thereof
US6359182B1 (en) 2000-10-26 2002-03-19 Duke University C-nitroso compounds and use thereof
US7179791B2 (en) * 2001-01-11 2007-02-20 Duke University Inhibiting GS-FDH to modulate NO bioactivity
EP1405636A4 (en) 2001-06-26 2009-04-15 Takeda Pharmaceutical FUNCTIONAL REGULATOR FOR RETINOID RELATIVE RECEPTOR
GB0119172D0 (en) * 2001-08-06 2001-09-26 Melacure Therapeutics Ab Phenyl pyrrole derivatives
GB0212785D0 (en) 2002-05-31 2002-07-10 Glaxo Group Ltd Compounds
EP1545515A1 (en) 2002-08-12 2005-06-29 Sugen, Inc. 3-pyrrolyl-pyridopyrazoles and 3-pyrrolyl-indazoles as novel kinase inhibitors
GB0229581D0 (en) * 2002-12-19 2003-01-22 Cyclacel Ltd Use
US20060270628A1 (en) 2003-04-29 2006-11-30 Jagattaran Das Antiinfective 1,2,3-triazole derivatives, process for their preparation and pharmaceutical compositions containing them
CA2528155A1 (en) * 2003-06-04 2005-01-06 Duke University Compositions and methods for modulating s-nitrosoglutathione reductase
US7754751B2 (en) * 2004-03-15 2010-07-13 Yung Shin Pharmaceutical Ind. Co., Ltd. Preferential inhibition of release of pro-inflammatory cytokines
MY144903A (en) 2004-06-17 2011-11-30 Novartis Ag Pyrrolopyridine derivatives and their use as crth2 antagonists
CA2573426C (en) 2004-07-30 2015-11-17 Exelixis, Inc. Pyrrole derivatives as pharmaceutical agents
CN101006052B (zh) * 2004-07-30 2013-11-06 埃克塞利希斯股份有限公司 作为药用制剂的吡咯衍生物
FR2881426B1 (fr) * 2005-02-03 2007-03-30 Aventis Pharma Sa Pyrolles et imidazoles substitues, compositions les contenant, procede de frabrication et utilisation
JP2006290791A (ja) 2005-04-11 2006-10-26 Astellas Pharma Inc アゾール置換スルホニルベンゼン誘導体
EP1928859A1 (en) 2005-06-17 2008-06-11 Carex SA Pyrazole derivates as cannabinoid receptor modulators
CN101223161A (zh) 2005-06-24 2008-07-16 健亚生物科技公司 治疗病毒感染的杂芳基衍生物
WO2007009083A2 (en) 2005-07-12 2007-01-18 Acadia Pharmaceuticals Inc. Compounds with activity at retinoic acid receptors
EP2581451B1 (en) 2007-12-13 2016-03-09 Indiana University Research and Technology Corporation Compounds for inhibiting mammalian s-nitrosoglutathione reductase
US20110104308A1 (en) 2008-05-09 2011-05-05 Duke University Treatment For Diseases Relying On Discovery That Thioredoxin Mediates Nitric Oxide
DK2315590T3 (da) * 2008-08-15 2012-11-19 N30 Pharmaceuticals Inc Pyrrolinhibitorer af S-nitrosoglutathionreduktase
ES2572615T3 (es) 2008-08-15 2016-06-01 Nivalis Therapeutics, Inc. Nuevos inhibidores pirrólicos de S-nitrosoglutatión reductasa como agentes terapéuticos
US8470857B2 (en) * 2008-08-15 2013-06-25 N30 Pharmaceuticals, Inc. Pyrrole inhibitors of S-nitrosoglutathione reductase as therapeutic agents
WO2010107476A1 (en) 2009-03-19 2010-09-23 Duke University Inhibiting gsnor
US8586624B2 (en) 2009-12-16 2013-11-19 N30 Pharmaceuticals, Inc. Thiophene inhibitors of S-nitrosoglutathione reductase
WO2013006635A1 (en) 2011-07-05 2013-01-10 N30 Pharmaceuticals, Llc Novel pyrrole inhibitors of s-nitrosoglutathione reductase as therapeutic agents for liver toxicity

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