HRP20100402T1 - Formamidni derivati korisni kao ardrenoceptor - Google Patents

Formamidni derivati korisni kao ardrenoceptor Download PDF

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HRP20100402T1
HRP20100402T1 HR20100402T HRP20100402T HRP20100402T1 HR P20100402 T1 HRP20100402 T1 HR P20100402T1 HR 20100402 T HR20100402 T HR 20100402T HR P20100402 T HRP20100402 T HR P20100402T HR P20100402 T1 HRP20100402 T1 HR P20100402T1
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hydroxyphenyl
formylamino
hydroxyethylamino
methylpropyl
phenyl
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HR20100402T
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Daniel Brown Alan
Edward Bunnage Mark
Alan Glossop Paul
James Kim
Alice Louise Lane Charlotte
Andrew Lewthwaite Russell
Anthony Price David
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Pfizer Inc.
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Priority claimed from PCT/IB2005/000619 external-priority patent/WO2005092840A1/en
Application filed by Pfizer Inc. filed Critical Pfizer Inc.
Publication of HRP20100402T1 publication Critical patent/HRP20100402T1/hr

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Abstract

Spoj opće formule (1), naznačen time što skupina (CH2)n-C(=O)Q1 je na meta ili para položaju,- R1 i R2 se neovisno bira između H i C1-C4 alkila;- n je 0, 1 ili 2;- Q1 je skupina koju se bira između, gdje p je 1 ili 2, a q je 1 ili 2, gdje je navedena skupina izborno premoštena s jednim atomom ugljika, i skupine *-NR8-Q2-A, gdje Q2 je C1-C4 alkilen, R8 je H ili C1-C4 alkil, a A je piridil, C3-C10 cikloalkil, gdje je navedeni cikloalkil izborno premošten s jednim ili više atoma ugljika, tetrahidropiranil, piperidinil, tetrahidrotiopiranil ili skupina- R3, R4, R5, R6 i R7 su isti ili različiti i bira ih se između H, C1-C4 alkila, OR9, SR9, SOR9, SO2R9, halogena, CO2R9 CF3, CN, OCF3, SO2NR9R10, CONR9R10, NR9R10, NHCOR10 i fenila, izborno supstituiranog s 1 do 3 skupine, koje se bira između OR9, halogena i C1-C4 alkila;- R9 i R10 su isti ili različiti i bira ih se između H ili C1-C4 alkil, a * predstavlja točku vezanja na karbonilnu skupinu; ili, ako je to prikladno, njegove farmaceutski prihvatljive soli i/ili izomeri, tautomeri, solvati ili njihove izotopne varijante. Patent sadrži još 23 patentna zahtjeva.

Claims (24)

1. Spoj opće formule (1), [image] naznačen time što skupina (CH2)n-C(=O)Q1 je na meta ili para položaju, – R1 i R2 se neovisno bira između H i C1-C4 alkila; – n je 0, 1 ili 2; – Q1 je skupina koju se bira između, [image] gdje p je 1 ili 2, a q je 1 ili 2, gdje je navedena skupina izborno premoštena s jednim atomom ugljika, [image] i skupine *-NR8-Q2-A, gdje Q2 je C1-C4 alkilen, R8 je H ili C1-C4 alkil, a A je piridil, C3-C10 cikloalkil, gdje je navedeni cikloalkil izborno premošten s jednim ili više atoma ugljika, tetrahidropiranil, piperidinil, tetrahidrotiopiranil ili skupina [image] – R3, R4, R5, R6 i R7 su isti ili različiti i bira ih se između H, C1-C4 alkila, OR9, SR9, SOR9, SO2R9, halogena, CO2R9 CF3, CN, OCF3, SO2NR9R10, CONR9R10, NR9R10, NHCOR10 i fenila, izborno supstituiranog s 1 do 3 skupine, koje se bira između OR9, halogena i C1-C4 alkila; – R9 i R10 su isti ili različiti i bira ih se između H ili C1-C4 alkil, a * predstavlja točku vezanja na karbonilnu skupinu; ili, ako je to prikladno, njegove farmaceutski prihvatljive soli i/ili izomeri, tautomeri, solvati ili njihove izotopne varijante.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što Q1 je skupina *-NH-Q2-A, gdje A je cikloheksil ili adamantil.
3. Spoj u skladu s patentnim zahtjevom 1, naznačen time što Q1 je skupina *-NH-Q2-A, gdje A je skupina [image] gdje R3, R4, R5, R6 i R7 su isti ili različiti i bira ih se između H, C1-C4 alkila, OR9, SR9, SOR9, SO2R9, halogena, CN, CO2R9, CF3, OCF3, SO2NR9R10, CONR9R10, NR9R10, NHCOR10 i fenila, izborno supstituiranog s 1 do 3 skupine, koje se bira između OR9, halogena i C1-C4 alkila, uz uvjet da najmanje 2 od R3 do R7 su H; gdje R9 i R10 su isti ili različiti i bira ih se između H ili C1-C4 alkila.
4. Spoj u skladu s patentnim zahtjevom 3, naznačen time što Q1 je skupina *-NH-Q2-A, gdje A je skupina [image] gdje R3, R4, R5, R6 i R7 su isti ili različiti i bira ih se između H, OH, CH3, OCH3, OCF3, OCH2-CH3, SCH3, N(CH3)2, N(C=O)CH3, C(=O)NH2, COOCH3, SO2CH3 SO2NH2, CN, halogena, CF3, te fenila, izborno supstituiranog s OH.
5. Spoj u skladu s patentnim zahtjevom 1, naznačen time što A je skupina [image] gdje jedan od R3 do R7 je OH ili fenil supstituiran s OH.
6. Spoj u skladu s patentnim zahtjevom 1, naznačen time što A je naftil, izborno suspstituiran s OH.
7. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 6, naznačen time što Q2 je -CH2-, -(CH2)2-, -(CH2)3-, -CH2-C(CH3)2- ili -C(CH3)2-.
8. Spoj u skladu s patentnim zahtjevom 7, naznačen time što Q2 je -CH2-.
9. Spoj u skladu s patentnim zahtjevom 1, naznačen time što Q1 je [image] gdje R3, R4, R5 i R6 su H.
10. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 9, naznačen time što R1 je H ili C1-C4 alkil i R2 je C1-C4 alkil.
11. Spoj u skladu s patentnim zahtjevom 10, naznačen time što R1 je H ili CH3 i R2 je H ili CH3.
12. Spoj u skladu s patentnim zahtjevom 1 do 11, naznačen time što n je 0 ili 1.
13. (R,R)-Stereoizomer, naznačen time što je stereoizomer spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 12.
14. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 13, naznačen time što (CH2)n-C(=O)Q1 skupina je na meta položaju.
15. Spoj u skladu s patentnim zahtjevom 1, naznačen time što ga se bira iz skupine koju čine N-Benzil-2-(3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)acetamid; N-(3,4-Dimetilbenzil)-2-(3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)acetamid; N-[2-(4-Klorfenil)etil]-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; N-[2-(2-Klorfenil)etil]-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(2-naftalen-1-iletil)benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(4-metilfenil)etil]benzamid; N-[2-(2,6-Dimetilfenil)etil]-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; N-[2-(2,3-Dimetilfenil)etil]-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropilbenzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(4-hidroksi-2,3-dimetilfenil)etil]benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(4-metoksifenil)etil]benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-fenetilbenzamid; N-Cikloheksilmetil-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; N-[5-((1R)-2-{1,1-Dimetil-2-[3-(piperidine-1-karbonil)fenil]etilamino}-1-hidroksietil)-2-hidroksifenil]formamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(3-trifluorometilfenil)etil]benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(3-fenilpropil)benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-indan-2-ilbenzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(2-piridin-2-iletil)benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksicyfenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(4-sulfamoilfenil)etil]benzamid; N-(4-Dimetilaminobenzil)-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetamid; N-[5-(2-{(1R)-2-[3-(3,4-Dihidro-1H-izokinoline-2-karbonil)fenil]-1,1-dimetiletilamino}-1-hidroksietil)-2-hidroksifenil]formamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(4'-hidroksibifenil-3-ilmetil)benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(4-hidroksi-2,5-dimetilfenil)etil]benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(4-hidroksi-3-metilfenil)etil]benzamid; N-(4-Acetilaminobenzil)-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetamid; 4-{[2-(3-{(2R)-2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetilamino]metil}benzamid; N-Adamantan-1-il-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(2-hidroksinaftalen-1-ilmetil)benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(4-hidroksi-3,5-dimetilbenzil)benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(6-hidroksinaftalen-2-ilmetil)benzamid; N-(3,6-Diklor-2-hidroksibenzil)-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; N-(3,4-Dimetilbenzil)-2-(3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]etil}fenil)acetamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-[2-(4-hidroksifenil)-2-metilpropil]benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}-N-(4'-hidroksibifenil-4-ilmetil)benzamid; N-Adamantan-1-il-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetamid; N-[5-(2-{2-[3-(10-Azatriciklo[6.3.1.02,7]dodeka-2(7),3,5-trien-10-karbonil)fenil]-1,1-dimetiletilamino}-1-hidroksietil)-2-hidroksifenil]formamid; 2-(3-{(2R)-2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(4'-hidroksibifenil-3-ilmetil)acetamid; Metilni ester 4-{[2-(3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)acetilamino]metil}benzojeve kieseline; 2-(3-{(2R)-2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)-N-(4-trifluorometoksibenzil)acetamid; N-(2-Klor-4-hidroksibenzil)-N-etil-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)acetamid; N-(2-Klor-4-hidroksibenzil)-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)acetamid; 2-(3-{(2R)-2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(4-hidroksi-3,5-dimetilbenzil)acetamid; 2-(3-{(2R)-2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(2-hidroksinaftalen-1-ilmetil)acetamid; N-(5-Klor-2-hidroksibenzil)-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetamid; N-(3,5-Diklor-2-hidroksibenzil)-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetamid; 2-(3-{(2R)-2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(6-hidroksinaftalen-2-ilmetil)acetamid; 2-(3-{(2R)-2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(4'-hidroksibifenil-4-ilmetil)acetamid; N-(4-Cijanobenzil)-2-(3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)acetamid; 2-(3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)-N-(4-methanesulfonilbenzil)acetamid; 2-(3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)-N-(4-metilsulfanilbenzil)acetamid; 2-(3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)-N-(4-trifluorometilbenzil)acetamid; 2-(3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)-N-(4'-hidroksibifenil-4-ilmetil)acetamid; N-[2-(5-Klor-2-hidroksifenil)etil]-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; 2-(3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)-N-(4'-hidroksibifenil-3-ilmetil)acetamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}-N-[2-(4-hidroksifenil)-2-metilpropil]benzamid; N-(2-Klor-4-hidroksibenzil)-2-(3-{(2R)-2-[(2R)-(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetamid; N-[2-(5-Klor-2-hidroksifenil)etil]-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid; 3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}-N-[2-(4-hidroksifenil)-2-metilpropil]benzamid; 2-(3-{2-[(2R)-2-(3-Formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)-N-(tetrahidro-tiopiran-4-il)acetamid; N-(5-Klor-2-hidroksibenzil)-2-(3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}fenil)acetamid; i N-{5-[(1R)-2-((1R)-2-{3-[3-(3,4-Dihidro-1H-izokinolin-2-il)-3-oksopropil]fenil}-1-metiletilamino)-1-hidroksietil]-2-hidroksifenil}formamid.
16. Spoj, naznačen time što je N-(5-klor-2-hidroksibenzil)-2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)acetamid ili njegova farmaceutski prihvatljiva sol ili solvat.
17. Spoj, naznačen time što je 2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(4-hidroksi-3,5-dimetilbenzil)acetamid ili njegova farmaceutski prihvatljiva sol ili solvat.
18. Spoj, naznačen time što je 2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(6-hidroksinaftalen-2-ilmetil)acetamid ili njegova farmaceutski prihvatljiva sol ili solvat.
19. Spoj, naznačen time što je 2-(3-{(2R)-2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]propil}fenil)-N-(4'-hidroksibifenil-4-ilmetil)acetamid ili njegova farmaceutski prihvatljiva sol ili solvat.
20. Spoj, naznačen time što je N-[2-(4-klorfenil)etil]-3-{2-[(2R)-2-(3-formilamino-4-hidroksifenil)-2-hidroksietilamino]-2-metilpropil}benzamid ili njegova farmaceutski prihvatljiva sol ili solvat.
21. Farmaceutski pripravak, naznačen time što u najmanjeu ruku sadrži djelotvornu količinu spoja formule (1) u skladu s bilo kojim od patentnih zahtjeva 1 do 20 ili njegovu farmaceutski prihvatljivu sol ili izvedeni oblik.
22. Spoj formule (1) u skladu s bilo kojim od patentnih zahtjeva 1 do 20 ili njegova farmaceutski prihvatljiva sol, izvedeni oblik ili pripravak, naznačen time što je namijenjen upotrebi kao medikament.
23. Upotreba spoja formule (1) u skladu s bilo kojim od patentnih zahtjeva 1 do 20 ili njegove farmaceutski prihvatljive soli, izvedenog oblika ili pripravaka, naznačena time što je navedeni spoj namijenjen proizvodnji lijeka za liječenje bolesti, poremećaja i stanja koje se bira iz skupine koju čine: • astma bilo kojeg tipa, etiologije ili patogeneze, osobito astma koja je član kojeg se bira iz skupine koju čine atopična astma, neatopična astma, alergijska astma, atopična bronhijalna astma posredovana IgE-om, bronhijalna astma, esencijalna astma, prava astma, intrinzična astma, uzrokovana patofiziološkim poremećajima, ekstrinzična astma, uzrokovana čimbenicima iz okoliša, esencijalna astma nepoznatog ili neočiglednog uzroka, neatopična astma, bronhitična astma, emfizematozna astma, astma izazvana fizičkom aktivnošću, astma izazvana alergenima, astma izazvana hladnim zrakom, profesionalna astma, infektivna astma, uzrokovana bakterijskom, gljivičnom, protozojskom ili virusnom infekcijom, nealergijska astma, incipijentna astma, sindrom sopljućeg djeteta i bronhiolitis, • kronična ili akutna bronhokonstrikcija, kronični bronhitis, začepljenje malih dišnih puteva, te emfizem, • opstruktivne ili upalne bolesti dišnih puteva bilo kojeg tipa, etiologije ili patogeneze, osobito opstruktivna ili upalna bolest dišnih puteva koja je član kojeg se bira iz skupine koju čine kronična eozinofilna pneumonija, kronična opstruktivna plućna bolest (COPD), COPD koji uključuje kronični bronhitis, plućni emfizem ili dispneju povezane ili nepovezane s COPD-om, COPD kod kojeg je karakteristično nepovratno, progresivno začepljenje dišnih puteva, sindrom respiratornog distresa kod odraslih (ARDS), pogoršanje preosjetljivosti dišnih puteva zbog terapije drugim lijekovima i bolest dišnih puteva povezana s plućnom hipertenzijom, • bronhitis bilo kojeg tipa, etiologije ili patogeneze, osobito bronhitis koji je član kojeg se bira iz skupine koju čine akutni bronhitis, akutni laringotrahealni bronhitis, arahidni bronhitis, kataralni bronhitis, krupozni bronhitis, suhi bronhitis, infektivni astmatični bronhitis, produktivni bronhitis, stafilokokni ili streptokokni bronhitis i vezikularni bronhitis, • akutna ozljada pluća, • bronhiektazija bilo kojeg tipa, etiologije ili patogeneze, osobito bronhiektazija koja je član kojeg se bira iz skupine koju čine cilindrična bronhiektazija, sakularna bronhiektazija, fuziformna bronhiektazija, kapilarna bronhiektazija, cistična bronhiektazija, suha bronhiektazija i folikularna bronhiektazija.
24. Kombinacija spoja u skladu s bilo kojim od patentnih zahtjeva 1 do 20, naznačena time što se navedeni spoj kombinira s jednim ili više drugih terapeutijskih sredstava, koja sebira između: (a) Inhibitora 5-lipoksigenaze (5-LO) ili antagonista 5-lipoksigenaza-aktivirajućeg proteina (FLAP), (b) Leukotrienskim antagonistima (LTRA), uključujući antagoniste LTB4, LTC4, LTD4 i LTE4, (c) Antagonistima histaminskih receptora, uključujući H1 i H3 antagoniste, (d) α1- i α2-adrenoceptorskim vazokonstrikcijskim simpatomimetskim agonistima koje se upotrebljava kao dekongestivi, (e) Antagonistima muskarinskog receptora M3 ili antikolinergičkim sredstvima, (f) Inhibitorima PDE, primjerice inhibitorima PDE3, PDE4 i PDE5, (g) Teofilinom, (h) Natrijevom kromoglikatom, (i) Inhibitorima COX, kako neselektivnim tako i selektivnim inhibitorima COX-1 ili COX-2 (NSAID), (j) Oralnim i inhalacijskim glukokortikosteroidima, (k) Monoklonskim protutijelima aktivnim protiv endogenih upalnih entiteta, (l) Sredstva protiv čimbenika tumorske nekroze (anti-TNF-α), (m) Inhibitorima adhezijskih molekula, uključujući antagoniste VLA-4, (n) Antagonistima kininskih receptora B1 i B2, (o) Imunosupresivnim sredstvima, (p) Inhibitorima matriksnih metaloproteaza (MMP), (q) Antagonistima tahikininskih receptora NK1, NK2 i NK3, (r) Inhibitorima elastaze, (s) Adenosine A2a receptor agonisti, (t) Inhibitorima urokinaze, (u) Spojevima koji djeluju na dopaminske receptore, primjerice D2 agonistima, (v) Modulatorima NFκβ puta, primjerice inhibitorima IKK, (w) Modulatorima citokinskih signalnih puteva, poput p38 MAP kinaze ili syk kinaze, (x) Sredstima koja se može klasificirati kao mukolitike ili antitusike, (y) Antibioticima, (z) Inhibitorima HDAC, i, (aa) Inhibitorima PI3-kinaze.
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IL178102A (en) 2011-08-31
UY28819A1 (es) 2005-10-31
KR20060122969A (ko) 2006-11-30
RS51438B (en) 2011-04-30
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MY144103A (en) 2011-08-15
SI1730103T1 (sl) 2010-09-30
GB0425054D0 (en) 2004-12-15
EA200601544A1 (ru) 2007-02-27
DE602005021472D1 (de) 2010-07-08
DK1730103T3 (da) 2010-08-16
PT1730103E (pt) 2010-07-21
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NL1028597C2 (nl) 2006-03-06
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EA010133B1 (ru) 2008-06-30
TW200531959A (en) 2005-10-01
CY1112549T1 (el) 2015-12-09
ES2343808T3 (es) 2010-08-10
PE20060264A1 (es) 2006-04-01
MA28480B1 (fr) 2007-03-01
TWI335312B (en) 2011-01-01
CA2560547C (en) 2011-02-01
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ATE469121T1 (de) 2010-06-15
NL1028597A1 (nl) 2005-09-26
NO20064806L (no) 2006-12-21
SV2005002056A (es) 2005-12-13
AR050236A1 (es) 2006-10-11
JP2007530524A (ja) 2007-11-01
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