HRP20130409T2 - 3-aminociklopentankarboksamidi kao modulatori kemokinskih receptora - Google Patents

3-aminociklopentankarboksamidi kao modulatori kemokinskih receptora Download PDF

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HRP20130409T2
HRP20130409T2 HRP20130409AT HRP20130409T HRP20130409T2 HR P20130409 T2 HRP20130409 T2 HR P20130409T2 HR P20130409A T HRP20130409A T HR P20130409AT HR P20130409 T HRP20130409 T HR P20130409T HR P20130409 T2 HRP20130409 T2 HR P20130409T2
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amino
anhydro
dideoxy
hept
diazabicyclo
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HRP20130409AT
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Rajesh Venkateswaran Devraj
Wei Huang
Robert Owen Hughes
Donald Joseph Rogier Jr.
John Isidro Trujillo
Steve Ronald Turner
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Pfizer Inc.
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Claims (15)

1. Spoj Formule I(a) ili I(b): [image] ili njegova farmaceutski prihvatljiva sol, naznačen time što: A je O ili CF2; W je CR13R14, C(O), CHOR15, CHF, CF2, O ili S; R1 je H ili (C1-C6)alkil, izborno supstituiran s 1-3 supstituenta, koje se bira između halogena, OH, CO2H, CO-(C1-C6)alkila ili (C1-C3)alkoksi; svaki od R2 i R3 je neovisno H, (C1-C6)alkil, (C1-C6) halogenalkil, halogen, (C3-C6)cikloalkil, CN, OH, OCOR12; gdje je navedeni (C1-C6)alkil izborno supstituiran s jednim ili više supstituenata, koje se bira između F, (C1-C3)alkoksi, OH, CN ili CO2R12; svaki od R8 i R9 je neovisno H, (C1-C6)alkil, (C1-C6)halogenalkil, (C3-C6)cikloalkil, CN, OH, OCOR12; gdje je navedeni (C1-C6)alkil izborno supstituiran s jednim ili više supstituenata, koje se bira između F, (C1-C3)alkoksi, OH, CN ili CO2R12; R2 i R8, uzeti zajedno, mogu tvoriti 5-8-eročlani prsten; R4 i R7, uzeti zajedno, mogu tvoriti 5-8-eročlani prsten; svaki od R4 i R5 je neovisno H, CN, (C1-C6)alkil, halogen, (C1-C3)alkoksi, (C1-C3)halogenalkoksi, (C3-C6)cikloalkil, OH, CO2R12, OCOR12, gdje je navedeni (C1-C6)alkil izborno supstituiran s jednim ili više supstituenata, koje se bira između F, (C1-C3)alkoksi, OH ili CO2R12; R6 i R7 svaki od je neovisno H, CN, (C1-C6)alkil, halogen, (C1-C3)alkoksi, (C1-C3)halogenalkoksi, (C3-C6)cikloalkil, OH, CO2R12, OCOR12, gdje je navedeni (C1-C6)alkil izborno supstituiran s jednim ili više supstituenata, koje se bira između F, (C1-C3)alkoksi, OH ili CO2R12; ili R2 i R3, zajedno s atomom ugljika na kojeg su vezani, tvore 3-7-eročlana spirociklilna skupina; ili R4 i R5, zajedno s atomom ugljika na kojeg su vezani, tvore 3-7-eročlana spirociklilna skupina; ili R3 i R4, zajedno s C atomima na koje su vezani, tvore kondenziranu 3-7-eročlanu cikloalkilnu skupinu ili 3-7-eročlanu heterocikloalkilnu skupinu; R10 je (C1-C6)alkil, (C1-C6)halogenalkil, (C1-C6)hidroksialkil, (C1-C6)alkoksi, (C3-C6)cikloalkil, hidroksi(C3-C6)cikloalkil, alkoksicikloalkil, OH, (C1-C5)heterociklil, amino, aril ili CN; R11 je aril ili heteroaril, gdje je navedeni R11 izborno neovisno supstituiran s jednim ili više (C1-C6)alkila, halogena, (C1-C6)halogenalkila, (C1-C3)alkoksi, OH, amino, C(O)NH2, NH2SO2, SF5 ili CN; R12 je H, (C1-C4)alkil ili (C3-C6)cikloalkil; R13 je H, halogen, (C1-C4)alkil, (C1-C4)alkoksi ili OH; R14 je H, halogen, (C1-C4)alkil, (C1-C4)alkoksi ili OH; i R15 je H, (C1-C6)alkil ili (C3-C6)cikloalkil, gdje je aril aromatska karbociklička skupina, poput fenila, bifenilila, indenila, naftila; ili aromatski karbocikl kondenziran s heterociklom poput benzotienila, benzofuranila, indolila, kinolinila, benzotiazola, benzooksazola, benzimidazola, izokinolinila, izoindolila, benzotriazola, indazola i akridinila.
2. Spoj Formule II: [image] ili njegova farmaceutski prihvatljiva sol, naznačen time što: R1 je H, (C1-C6)alkil ili (C3-C6)cikloalkil, gdje je navedeni (C1-C6)alkil izborno supstituiran s halogenom, CN, C(O)OH ili OH; R2 je (C1-C6)alkil, (C1-C6)halogenalkil ili (C3-C6)cikloalkil; R3, R4, R5, R6, R7, R8 i R9 su neovisno H, C1-C4 alkil, CN, halogen ili amino; R10 je (C16-C)alkil, (C1-C6)halogenalkil, (C1-C6)hidroksialkil, (C1-C6)alkoksi, (C3-C6)cikloalkil, hidroksi(C3-C6)cikloalkil, alkoksi (C3-C6)cikloalkil, OH, (C1-C5)heterociklil, amino, aril ili CN; R11 je aril ili heteroaril, gdje je navedeni R11 izborno neovisno supstituiran s jednim ili više (C1-C6)alkila, halogena, (C1-C6)halogenalkila, (C1-C6)alkoksi, OH, amino, C(O)NH2, NH2SO2, SF5 ili CN; W je CR13R14, C(O), CHOR15, CHF, CF2, O ili S; R13 i R14 su neovisno H, halogen, (C1-C4)alkil, (C1-C4)alkoksi ili OH; i R15 je H, (C1-C6)alkil ili (C3-C6)cikloalkil, gdje je aril aromatska karbociklička skupina, poput fenila, bifenilila, indenila, naftila; ili aromatski karbocikl kondenziran s heterociklom poput benzotienila, benzofuranila, indolila, kinolinila, benzotiazola, benzooksazola, benzimidazola, izokinolinila, izoindolila, benzotriazola, indazola i akridinila.
3. Spoj u skladu s patentnim zahtjevom 2, ili njegova farmaceutski prihvatljiva sol, naznačen time što: R1 je H ili (C1-C6)alkil; R2 je (C1-C6)alkil ili (C1-C6)halogenalkil; svaki od R3, R4, R5, R6, R7, R8 i R9 je H; R11 je [image] , gdje su X, Y, Z, Q i D neovisno N ili CR16, a gdje 0, 1, 2 ili 3 od X, Y, Z, Q i D su N; i gdje se T, U i V neovisno bira između CH, N, S ili O, uz uvjet da T i U nisu oba istodobno O ili S; svaki R18 je neovisno H, halogen, (C1-C6)alkil, (C1-C6)halogenalkil, (C1-C6)alkoksi ili CN; R17 je H, (C1-C6)alkil, (C1-C6)halogenalkil ili (C1-C6)alkoksi; i W je CR13R14, C(O), CHOR15, CHF ili CF2.
4. Spoj u skladu s patentnim zahtjevom 3, ili njegova farmaceutski prihvatljiva sol, naznačen time što R2 je metil.
5. Spoj ili sol u skladu s patentnim zahtjevom 4, naznačen time što R10 je [image] [image] [image]
6. Spoj u skladu s patentnim zahtjevom 3, ili njegova farmaceutski prihvatljiva sol, naznačen time što R11 je [image] [image] [image] [image] [image] [image] [image] ili [image]
7. Spoj u skladu s patentnim zahtjevom 5, ili njegova farmaceutski prihvatljiva sol, naznačen time što R11 je [image] [image] [image] [image] [image] [image] [image] ili [image]
8. Spoj ili sol u skladu s patentnim zahtjevom 7, naznačen time što R10 je [image] i R11 je [image] .
9. Spoj u skladu s patentnim zahtjevom 1 ili 2, naznačen time što ga se bira iz skupine koju čine: 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-etil-3-({(1S,4S)-5-[4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-etil-3-({(1S,4S)-5-[4-(trifluormetil)pirimidin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-etil-3-({(1S,4S)-5-[6-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-etil-3-({(1S,4S)-5-[6-(trifluormetil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2.3-dideoksi-3-{[(1R,3S)-3-etil-3-({(1S,4S)-5-[2-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-0-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-etil-3-({(1S,4S)-5-[6-(tritluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-etil-3-([(1S,4S)-5-[2-(trifluormetil)piridin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-etil-3-({(1S,4S)-5-[3-fluor-4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-metil-3-({(1S,4S)-5-[4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil}ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-metil-3-({(1S,4S)-5-[6-(trifluormetil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[4-(trifluormetil)pirimidin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[6-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il]karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[6-(trifluormetil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il]karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[2-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-(6-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[2-(trifluormetil)piridin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[5-(trifluormetil)pindazin-3-il]-2,5-diazabiciklo[2.2.1]hept-2-il]karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[2,6-bis(trifluormetil)piridin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)-3-izopropilciklopentil]amino}-2,3-dideoksi-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-({(1S,4S)-5-[3-fluor-4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)-3-izopropilciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[6-metil-4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-izopropil-3-({(1S,4S)-5-[3-(trifluormetil)fenil]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-({(1S,4S)-5-[3-fluor-5-(trifluormetil)fenil]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)-3-izopropilciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(2,2-difluoretil)-3-({(1S,4S)-5-[6-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(2,2-difluoretil)-3-({(1S,4S)-5-[4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(2,2-difluoretil)-3-({(1S,4S)-5-[2-(trifluormetil)piridin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(2,2-difluoretil)-3-({(1S,4S)-5-[4-(trifluormetil)pirimidin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(2,2-difluoretil)-3-({(1S,4S)-5-[6-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[{1R,3S)-3-(2,2-difluoretil)-3(1S,4S)-5-[6-(trifluormetil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(2,2-difluoretil)-3-({(1S,4S)-5-[2-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(2,2-difluoretil)-3-({(1S,4S)-5-[5-(trifluormetil)piridazin-3-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-(6-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-(4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino]-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-[2-(trifluormetil)piridin-4-il)-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-[4-(trifluormetil)pirimidin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-[6-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-[6-(trifiuorometil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-[2-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-4-O-metil-3-{[(1R,3S)-3-(2,2,2-trifluoretil)-3-({(1S,4S)-5-[5-(trifluormetil)piridazin-3-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1S,4S)-4-izopropill-4-({(1S,4S)-5-(4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopent-2-en-1-il]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1S,4S)-4-izopropil]-4-({(1S,4S)-5-[4-(trifluormetil)pirimidin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopent-2-en-1-il]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1S,4S)-4-izopropil]-4-({(1S,4S)-5-[6-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il]karbonil)ciklopent-2-en-1-il]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1S,4S)-4-izopropil]-4-({(1S,4S)-5-[6-(trifluormetil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopent-2-en-1-il]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-3-{[(1R,3S)-3-{[(1S,4S)-5-(tert-butoksikarbonil)-2,5-diazabiciklo[2.2.1]hept-2-il]karbonil]-3-etilciklopentil]amino}-2,3-dideoksi-4-O-metil-d-erythro-pentitol; 1,5-anhidro-3-{[(1R,3S)-3-{[(1S,4S)-5-(tert-butoksikarbonil)-2,5-diazabiciklo[2.2.1]hept-2-il]karbonil}-3-(2,2,2-trifluoretil)ciklopentil]amino}-2,3-dideoksi-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(1-hidroksiciklobutil)-3-({(1S,4S)-5-[6-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(1-hidroksiciklobutil)-3-({(1S,4S)-5-[4-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(1-hidroksiciklobutil)-3-({(1S,4S)-5-[4-(trifluormetil)pirimidin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino]-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(1-hidroksiciklobutil)-3-({(1S,4S)-5-[2-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(1-hidroksiciklobutil)-3-({(1S,4S)-5-[6-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-hidroksiciklobutil)-3-({(1S,4S)-5-[6-(trifluormetil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[(1R,3S)-3-(1-hidroksiciklobutil)-3-({(1S,4S)-5-[2-(trifluormetil)piridin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metil-d-erythro-pentitol; 1,5-anhidro-2,3-dideoksi-3-{[3-(1-hidroksi-1-metiletil)-3-({5-[4-{trifluormetil}piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metilpentitol; 1,5-anhidro-2,3-dideoksi-3-{(3-(1-hidroksi-1-metiletil)-3-({5-[6-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metilpentitol; 1,5-anhidro-2,3-dideoksi-3-{[3-(1-hidroksi-1-metiletil)-3-({5-[4-(trifluormetil)pirimidin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il)karbonil)clopentil]amino}-4-O-metilpentitol; 1,5-anhidro-2,3-dideoksi-3-{[3-(1-hidroksi-1-metiletil)-3-({5-[5-(trifluormetil)piridazin-3-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metilpentitol; 1,5-anhidro-2,3-dideoksi-3-{[3-(1-hidroksi-1-metiletil)-3-({5-[2-(trifluormetil)pirimidin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metilpentitol; 1,5-anhidro-2,3-dideoksi-3-{[3-(1-hidroksi-1-metiletil)-3-({5-[6-(trifluormetil)piridin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metilpentitol; 1,5-anhidro-2,3-dideoksi-3-{[3-(1-hidroksi-1-metiletil)-3-({5-[2-(trifluormetil)piridin-4-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metilpentitol; i 1,5-anhidro-2,3-dideoksi-3-{[3-(1-hidroksi-1-metiletil}-3-({5-[6-(trifluormetil)pirazin-2-il]-2,5-diazabiciklo[2.2.1]hept-2-il}karbonil)ciklopentil]amino}-4-O-metilpentitol; ili njegova farmaceutski prihvatljiva sol.
10. Spoj u skladu s patentnim zahtjevom 2, naznačen time što ima formulu: [image] ili njegova farmaceutski prihvatljiva sol.
11. Spoj u skladu s patentnim zahtjevom 2, naznačen time što ima formulu: [image] ili njegova farmaceutski prihvatljiva sol.
12. Pripravak, naznačen time što sadrži spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 11, ili njegovu farmaceutski prihvatljivu sol; te podlogu.
13. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačeni time što su namijenjeni upotrebi u medicini.
14. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačeni time što su namijenjeni upotrebi u liječenju bolesti povezane s ekspresijom ili aktivnošću kemokinskog receptora kod pacijenta.
15. Spoj ili sol u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačeni time što su namijenjeni upotrebi u liječenju reumatoidnog artritisa, ateroskleroze, lupusa, multiple skleroze, boli, odbacivanja presatka, dijabetesa, fibroze jetre, virusne bolesti, raka, astme, sezonskog i nesezonskog alergijskog rinitisa, sinusitisa, konjunktivitisa, staračke degeneracije makule, alergije na hranu, skombroidnog otrovanja, psorijaze, nedizdiferencirane spondiloartropatije, gihta, koprivnjače, svrbeža, ekzema, upalne bolesti crijeva, trombotske bolesti, upale srednjeg uha, fibroze, ciroze jetre, srčane bolest, Alzheimerove bolest, sepse, restenoze, Crohnove bolesti, ulceroznog kolitisa, sindroma iritabilnih crijeva, bolesti pluća zbog preosjetljivosti, fibroze pluća uzrokovane lijekovima, kronične opstruktivne plućne bolest, artritisa, nefritisa, atopičnog dermatitisa, inzulta, akutne ozljede živca, sarkoidoze, hepatitisa, endometrioze, neuropatske boli, pneumonitisa zbog preosjetljivosti, eozinofilnih pneumonija, preosjetljivosti odgođenog tipa, intersticijske bolesti pluća, poremećaja oka ili pretilosti.
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CU20110121A7 (es) 2013-05-31
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RS52810B (en) 2013-10-31
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