HRP20100008T1 - Supstituirani piridinil i pirimidinil derivati kao modulatori metabolizma i liječenje poremećaja povezanih s istima - Google Patents

Supstituirani piridinil i pirimidinil derivati kao modulatori metabolizma i liječenje poremećaja povezanih s istima Download PDF

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HRP20100008T1
HRP20100008T1 HR20100008T HRP20100008T HRP20100008T1 HR P20100008 T1 HRP20100008 T1 HR P20100008T1 HR 20100008 T HR20100008 T HR 20100008T HR P20100008 T HRP20100008 T HR P20100008T HR P20100008 T1 HRP20100008 T1 HR P20100008T1
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pyridin
methoxy
yloxy
piperidine
carboxylic acid
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Hurst David
M. Jones Robert
Siu-Ting Wong Amy
Lehmann Juerg
Shin Young-Jun
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Arena Pharmaceuticals
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Abstract

Pripravak , naznačen time, da sadrži: (a) inhibitor dipeptidil peptidaze IV (DPP-IV); te (b) spoj izabran među spojevima Formule (Ia) i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: gdje: X je N ili CR8 pri čemu R8 je H ili halogen; Y je NH ili O; Z je CH ili N; R1 je karbo-C1-6-alkoksi, oksadiazolil ili pirimidinil, pri čemu je svaki od navedenih karbo-C1-6-alkoksi, oksadiazolil i pirimidinil po izboru supstituiran s 1 ili 2 supstituenda neovisno izabranih između: C1-4 akil, C1-4 alkoksi i C3-5 cikloalkil; R2 je H ili C1-4 alkil; R3 je C1-4 alkoksi, O-C2-4-alkinil ili hidroksil; R4 je izabran između: H, C1-4 akoksi, C1-4 akil, C2-4 akinil i halogen; iliR5 je izabran iz skupine koju čine: C1-4 acilsulfonamid, C1-4 akoksi, C1-4 akil, C1-4 akilamino, C1-4 akilsulfonil, C1-4 akiltio, cijano, heterociklil, di-C1-4diakilamino i sulfonamid, pri čemu navedeni C1-4 akoksi, C1-4 akil, C1-4 akilamino, C1-4 akilsulfonil, C1-4 akiltio, di-C1-4-diakilamino i heterociklil su po izboru supstituirani s 1 ili 2 supstituenda neovisno izabrana između: C2-4 alkinil, C1-4 alkoksi, C1-4 alkilkarboksamid, C1-4 alkilsulfonil, C3-5 cikloalkil, C3-5 cikloalkiloksi, di-C1-4 alkilkarboksamid, hidroksil i fosfonooksi, pri čemu je navedeni C1-4 alkilkarboksamid po izboru supstituiran s hidroksil; iliR5 je skupina Formule (A): gdje: "m", "n" i "q" su svaki neovisno 0, 1, 2, ili 3; "r" je 0, 1 ili 2; te "t" je 0 ili 1; R6 je H ili halogen; teR7 je H ili C1-4 alkil. Patent sadrži još 61 patentni zahtjev.

Claims (62)

1. Pripravak , naznačen time, da sadrži: (a) inhibitor dipeptidil peptidaze IV (DPP-IV); te (b) spoj izabran među spojevima Formule (Ia) i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: [image] gdje: X je N ili CR8 pri čemu R8 je H ili halogen; Y je NH ili O; Z je CH ili N; R1 je karbo-C1-6-alkoksi, oksadiazolil ili pirimidinil, pri čemu je svaki od navedenih karbo-C1-6-alkoksi, oksadiazolil i pirimidinil po izboru supstituiran s 1 ili 2 supstituenda neovisno izabranih između: C1-4 akil, C1-4 alkoksi i C3-5 cikloalkil; R2 je H ili C1-4 alkil; R3 je C1-4 alkoksi, O-C2-4-alkinil ili hidroksil; R4 je izabran između: H, C1-4 akoksi, C1-4 akil, C2-4 akinil i halogen; ili R5 je izabran iz skupine koju čine: C1-4 acilsulfonamid, C1-4 akoksi, C1-4 akil, C1-4 akilamino, C1-4 akilsulfonil, C1-4 akiltio, cijano, heterociklil, di-C1-4diakilamino i sulfonamid, pri čemu navedeni C1-4 akoksi, C1-4 akil, C1-4 akilamino, C1-4 akilsulfonil, C1-4 akiltio, di-C1-4-diakilamino i heterociklil su po izboru supstituirani s 1 ili 2 supstituenda neovisno izabrana između: C2-4 alkinil, C1-4 alkoksi, C1-4 alkilkarboksamid, C1-4 alkilsulfonil, C3-5 cikloalkil, C3-5 cikloalkiloksi, di-C1-4 alkilkarboksamid, hidroksil i fosfonooksi, pri čemu je navedeni C1-4 alkilkarboksamid po izboru supstituiran s hidroksil; ili R5 je skupina Formule (A): [image] gdje: „m“, „n“ i „q“ su svaki neovisno 0, 1, 2, ili 3; „r“ je 0, 1 ili 2; te „t“ je 0 ili 1; R6 je H ili halogen; te R7 je H ili C1-4 alkil.
2. Pripravak u skladu sa zahtjevom 1, naznačen time, da X je N.
3. Pripravak u skladu sa zahtjevom 1 ili 2, naznačen time, da Y je NH.
4. Pripravak u skladu sa zahtjevom 1 ili 2, naznačen time, da Y je O.
5. Pripravak u skladu s bilo kojim zahtjevom 1 do 4, naznačen time, da Z je CH.
6. Pripravak u skladu s bilo kojim zahtjevom 1 do 4, naznačen time, da Z je N.
7. Pripravak u skladu s bilo kojim zahtjevom 1 do 6, naznačen time, da R1 je karbo-C1-6-alkoksi po izboru supstituiran s C3-5cikloalkil.
8. Pripravak u skladu s bilo kojim zahtjevom 1 do 6, naznačen time, da je R1 izabran iz skupine koju čine: C(O)OCH2CH3, C(O)OCH(CH3)2, C(O)OCH(CH3)(CH2CH3), C(O)OCH2-ciklopropil i C(O)OCH(CH3)(ciklopropil).
9. Pripravak u skladu s bilo kojim zahtjevom 1 do 6, naznačen time, da R1 je oksadiazolil po izboru supstituiran s jednom C1-4 alkil skupinom.
10. Pripravak u skladu s bilo kojim zahtjevom 1 do 6, naznačen time, da R1 je pirimidinil po izboru supstituiran s jednom C1-4 alkoksi skupinom.
11. Pripravak u skladu s bilo kojim zahtjevom 1 do 10, naznačen time, da R2 je H.
12. Pripravak u skladu s bilo kojim zahtjevom 1 do 11, naznačen time, da R3 je C1-4 alkoksi.
13. Pripravak u skladu s bilo kojim zahtjevom 1 do 11, naznačen time, da R3 je OCH3 ili OCH2CH3.
14. Pripravak u skladu s bilo kojim zahtjevom 1 do 13, naznačen time, da je R4 izabran iz skupine koju čine: H, OCH3, CH3, CH2CH3, F, Cl i C≡CH.
15. Pripravak u skladu s bilo kojim zahtjevom 1 do 14, naznačen time, da je R5 izabran iz skupine koju čine: OCH2CH2CH3, OCH2CH2CH2OH, S(O)2CH3, CH2CH2S(O)2CH3, NHCH2CH2OH, cijano, CH2CH2OCH3, CH2CH2OH, CH2CH2CH(CH3)OH, CH2CH2OP(O)(OH)2, S(O)2NHC(O)CH2CH3, CH2CH2O-ciklopropil, NHCH2CH2OCH3, OCH2CH2S(O)2CH3, NHCH2CH(CH3)OH, CH2CH2CH2OH, CH2CH2CH2OP(O)(OH)2, NHCH2CH(CH3)S(O)2CH3, N(CH3)CH2CH(CH3)S(O)2CH3, 3-metansulfonil-pirolidin-1-il, 3-metansulfonil-piperidin-1-il, CH2C(O)N(CH3)2, 3-metansulfonil-azetidin-1-il, CH2C(O)NHCH2CH2OH, SCH2CH2OH, S(O)2CH2CH2OP(O)(OH)2, S(O)2CH2CH3, NHCH2CH(OH)CH2OH, S(O)2CH2CH2OH, OCH2CH2OP(O)(OH)2, OCH2CH2CH2OP(O)(OH)2 i S(O)2NH2.
16. Pripravak u skladu s bilo kojim zahtjevom 1 do 14, naznačen time, da je R5 izabran iz skupine koju čine: OCH2CH2CH2OH, S(O)2CH3, CH2CH2S(O)2CH3, NHCH2CH2OH, cijano, CH2CH2OH, CH2CH2CH(CH3)OH, CH2CH2OP(O)(OH)2, S(O)2NHC(O)CH2CH3, CH2CH2CH2OH, S(O)2CH2CH3, NHCH2CH(OH)CH2OH, amino, NHCH2CH3, NHCH(CH3)2 i NHCH(CH3)CH2CH3.
17. Pripravak u skladu s bilo kojim zahtjevom 1 do 16, naznačen time, da R6 je H.
18. Pripravak u skladu s bilo kojim zahtjevom 1 do 17, naznačen time, da R7 je H.
19. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među spojevima koji imaju Formulu (IIa) i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: [image] gdje: Y je NH ili O; R1 je karbo-C1-6-alkoksi po izboru supstituiran s C3-5 cikloalkil; R2 je H ili CH3; R3 je C1-4 alkoksi; R4 je izabran između: H, OCH3, CH3, CH2CH3, F i Cl; R5 je izabran između: OCH2CH2CH3, OCH2CH2CH2OH, S(O)2CH3, CH2CH2S(O)2CH3, NHCH2CH2OH, cijano, CH2CH2OCH3, CH2CH2OH, CH2CH2CH(CH3)OH, CH2CH2OP(O)(OH)2, S(O)2NHC(O)CH2CH3, CH2CH2O-ciklopropil, NHCH2CH2OCH3, OCH2CH2S(O)2CH3, NHCH2CH(CH3)OH, CH2CH2CH2OH, CH2CH2CH2OP(O)(OH)2, NHCH2CH(CH3)S(O)2CH3, N(CH3)CH2CH(CH3)S(O)2CH3, 3-metansulfonil-pirolidin-1-il, 3-metansulfonil-piperidin-1-il, CH2C(O)N(CH3)2, 3-metansulfonil-azetidin-1-il, CH2C(O)NHCH2CH2OH, SCH2CH2OH, S(O)2CH2CH2OP(O)(OH)2, S(O)2CH2CH3, NHCH2CH(OH)CH2OH, S(O)2CH2CH2OH, OCH2CH2OP(O)(OH)2, OCH2CH2CH2OP(O)(OH)2 i S(O)2NH2; R6 je H ili F; te R7 je H ili CH3.
20. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među spojevima koji imaju Formulu (IIc) i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: [image] gdje: R1 je karbo-C1-6-alkoksi po izboru supstituiran s C3-5 cikloalkil; R2 je H ili CH3; R3 je C1-4 alkoksi; R4 je izabran između: H, OCH3, CH3, CH2CH3, F i Cl; R5 je izabran između: OCH2CH2CH3, OCH2CH2CH2OH, S(O)2CH3, CH2CH2S(O)2CH3, NHCH2CH2OH, cijano, CH2CH2OCH3, CH2CH2OH, CH2CH2CH(CH3)OH, CH2CH2OP(O)(OH)2, S(O)2NHC(O)CH2CH3, CH2CH2O-ciklopropil, NHCH2CH2OCH3, OCH2CH2S(O)2CH3, NHCH2CH(CH3)OH, CH2CH2CH2OH, CH2CH2CH2OP(O)(OH)2, NHCH2CH(CH3)S(O)2CH3, N(CH3)CH2CH(CH3)S(O)2CH3, 3-metansulfonil-pirolidin-1-il, 3-metansulfonil-piperidin-1-il, CH2C(O)N(CH3)2, 3-metansulfonil-azetidin-1-il, CH2C(O)NHCH2CH2OH, SCH2CH2OH, S(O)2CH2CH2OP(O)(OH)2, S(O)2CH2CH3, NHCH2CH(OH)CH2OH, S(O)2CH2CH2OH, OCH2CH2OP(O)(OH)2, OCH2CH2CH2OP(O)(OH)2 i S(O)2NH2; R6 je H ili F; te R7 je H ili CH3.
21. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među spojevima koji imaju Formulu (IIe) i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: [image] gdje: R1 je karbo-C1-6-alkoksi po izboru supstituiran s C3-5 cikloalkil; R2 je H ili CH3; R3 je C1-4 alkoksi; R4 je izabran između: H, OCH3, CH3, CH2CH3, F i Cl; R5 je izabran između: OCH2CH2CH3, OCH2CH2CH2OH, S(O)2CH3, CH2CH2S(O)2CH3, NHCH2CH2OH, cijano, CH2CH2OCH3, CH2CH2OH, CH2CH2CH(CH3)OH, CH2CH2OP(O)(OH)2, S(O)2NHC(O)CH2CH3, CH2CH2O-ciklopropil, NHCH2CH2OCH3, OCH2CH2S(O)2CH3, NHCH2CH(CH3)OH, CH2CH2CH2OH, CH2CH2CH2OP(O)(OH)2, NHCH2CH(CH3)S(O)2CH3, N(CH3)CH2CH(CH3)S(O)2CH3, 3-metansulfonil-pirolidin-1-il, 3-metansulfonil-piperidin-1-il, CH2C(O)N(CH3)2, 3-metansulfonil-azetidin-1-il, CH2C(O)NHCH2CH2OH, SCH2CH2OH, S(O)2CH2CH2OP(O)(OH)2, S(O)2CH2CH3, NHCH2CH(OH)CH2OH, S(O)2CH2CH2OH, OCH2CH2OP(O)(OH)2, OCH2CH2CH2OP(O)(OH)2 i S(O)2NH2; R6 je H ili F; te R7 je H ili CH3.
22. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među spojevima koji imaju Formulu (IIe) i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: [image] gdje: R1 je karbo-C1-6-alkoksi po izboru supstituiran s C3-5 cikloalkil; R2 je H ili CH3; R3 je C1-4 alkoksi; R4 je izabran između: H, OCH3, CH3, CH2CH3, F i Cl; R5 je izabran između: OCH2CH2CH2OH, S(O)2CH3, CH2CH2S(O)2CH3, NHCH2CH2OH, cijano, CH2CH2OH, CH2CH2CH(CH3)OH, CH2CH2OP(O)(OH)2, S(O)2NHC(O)CH2CH3, CH2CH2CH2OH, S(O)2CH2CH3, NHCH2CH(OH)CH2OH i S(O)2NH2; R6 je H ili F; te R7 je H ili CH3.
23. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među spojevima koji imaju Formulu (IIg) i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: [image] gdje: R1 je karbo-C1-6-alkoksi po izboru supstituiran s C3-5 cikloalkil; R2 je H ili CH3; R3 je C1-4 alkoksi; R4 je izabran između: H, OCH3, CH3, CH2CH3, F i Cl; R5 je izabran između: OCH2CH2CH3, OCH2CH2CH2OH, S(O)2CH3, CH2CH2S(O)2CH3, NHCH2CH2OH, cijano, CH2CH2OCH3, CH2CH2OH, CH2CH2CH(CH3)OH, CH2CH2OP(O)(OH)2, S(O)2NHC(O)CH2CH3, CH2CH2O-ciklopropil, NHCH2CH2OCH3, OCH2CH2S(O)2CH3, NHCH2CH(CH3)OH, CH2CH2CH2OH, CH2CH2CH2OP(O)(OH)2, NHCH2CH(CH3)S(O)2CH3, N(CH3)CH2CH(CH3)S(O)2CH3, 3-metansulfonil-pirolidin-1-il, 3-metansulfonil-piperidin-1-il, CH2C(O)N(CH3)2, 3-metansulfonil-azetidin-1-il, CH2C(O)NHCH2CH2OH, SCH2CH2OH, S(O)2CH2CH2OP(O)(OH)2, S(O)2CH2CH3, NHCH2CH(OH)CH2OH, S(O)2CH2CH2OH, OCH2CH2OP(O)(OH)2, OCH2CH2CH2OP(O)(OH)2 i S(O)2NH2; R6 je H ili F; te R7 je H ili CH3.
24. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među slijedećim spojevima i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: 4-[6-(4-metansulfonil-2-metoksi-fenilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{5-metoksi-6-[6-(2-metoksi-etil)-2-metil-piridin-3-ilamino]-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-metansulfonil-etil)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline 1-ciklopropil-etil ester; 4-[6-(2-fluoro-4-metansulfonil-fenilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-[6-(4-cijano-2-fluoro-fenilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-hidroksi-etil)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-metansulfonil-etil)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{5-metoksi-6-[6-(2-metoksi--etilamino)-2-metil-piridin-3-ilamino]-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-metansulfonil-etoksi)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-hidroksi-propilamino)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(3-hidroksi-propil)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{5-metoksi-6-[2-metil-6-(3-fosfonooksi-propil)-piridin-3-ilamino]-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-metansulfonil-etilamino)-2-metoksi-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-metansulfonil-propilamino)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[6-(2-dimetilkarbamoilmetil-2-metil-piridin-3-ilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-(6-{2-fluoro-4-[(2-hidroksi-etilkarbamiol)-metil]-fenilamino}-5-metoksi-pirimidin-4-iloksi)-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-metansulfonil-etilamino)-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[2-floro-4-(2-hidroksi-etilsulfonil)-fenilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2,3-dihidroksi-propilamino)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-hidroksi-etoksi)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{5-metoksi-6-[2-metil-6-(2-fosfonooksi-etoksi)-piridin-3-ilamino]-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(3-hidroksi-propoksi)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; te 4-{5-metoksi-6-[2-metil-6-(3-fosfonooksi-propoksi)-piridin-3-ilamino]-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester.
25. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među slijedećim spojevima i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: 4-[2-(2-fluoro-4-propoksi-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[2-fluoro-4-(2-hidroksi-etil)-fenilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[5-fluoro-2-(2-fluoro-4-metansulfonil-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[2-etil-4-(2-metansulfonil-etil)-fenilamino]-3-metoksi-piridin-4-iloksi}-2-metil-piperidin-1-karboksilne kiseline izopropil ester; 4-{5-fluoro-2-[6-(2-hidroksi-etoksi)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[2-fluoro-4-(2-metansulfonil-etil)-fenilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-hidroksi-etilamino)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(4-cijano-2-fluoro-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(2-kloro-4-cijano-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-metansulfonil-etil)-2-metoksi-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-metansulfonil-etil)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-hidroksi-etil)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(3-hidroksi-butil)-2-metoksi-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[2-fluoro-4-(2-hidroksi-etoksi)-fenilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{3-etoksi-2-[2-fluoro-4-(2-fosfonooksi-etil)-fenilamino]-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[3-metoksi-2-(2-metoksi-4-propionilsulfamoil-fenilamino)-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(2,5-difluoro-4-propoksi-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; (2-fluoro-4-metansulfonil-fenil)-{4-[1-(5-izopropil-[1,2,4]oksadiazol-3-il)-piridin-4-iloksi]-3-metoksi-piridin-2-il}-amin; (2-fluoro-4-metansulfonil-fenil)-{3-metoksi-4-[1-(5-metoksi-pirimidin-2-il)-piperidin-4-iloksi]-piridin-2-il}-amin; 4-{2-[6-(2-ciklopropoksi-etil)-2-metoksi-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(2-kloro-4-metansulfonil-fenilamino)-5-fluoro-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-[3-etoksi-2-(4-metansulfonil-2-metoksi-fenilamino)-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(5-fluoro-2-metil-4-propoksi-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-metansulfonil-etil)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(2-fluoro-4-metansulfonil-fenilamino)-3-hidroksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(2-kloro-4-propoksi-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{3-metoksi-2-[2-metil-6-(2-fosfonooksi-etil)-piridin-3-ilamino]-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-metansulfonil-etilamino)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-(2-{6-[(2-metansulfonil-etil)-metil-amino]-2-metil-piridin-3-ilamino}-3-metoksi-piridin-4-iloksi)-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(3-metansulfonil-pirolidin-1-il)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(3-metansulfonil-6'-metil-3,4,5,6-tetrahidro-2H-[1,2']bipiridinil-5'-ilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(3-metansulfonil-azetidin-1-il)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[3-etiniloksi-2-(2-fluoro-4-metansulfonil-fenilamino)-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[2-fluoro-4-(2-fosfonooksi-etansulfonil)-fenilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[2-(4-etansulfonil-2-fluoro-fenilamino)-3-metoksi-piridin-4-iloksi]-piperidin-1-karboksilne kiseline sec-butil ester; 4-{2-[6-(2,3-dihidroksi-propilamino)-4-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-hidroksi-etilsulfonil)-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[2-fluoro-4-(2-hidroksi-etansulfonil)-fenilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-hidroksi-etoksi)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{3-metoksi-2-[2-metil-6-(2-fosfonooksi-etoksi)-piridin-3-ilamino]-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(3-hidroksi-propoksi)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{3-metoksi-2-[2-metil-6-(3-fosfonooksi-propoksi)-piridin-3-ilamino]-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[3-metoksi-2-(2-metoksi-4-sulfamoil-fenilamino)-piridin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[2-fluoro-4-(3-fosfonooksi-propil)-fenilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-hidroksi-etil)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{3-metoksi-2-[2-metil-6-(2-fosfonooksi-etil)-piridin-3-ilamino]-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(3-hidroksi-propil)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; te 4-{3-metoksi-2-[2-metil-6-(3-fosfonooksi-propil)-piridin-3-ilamino]-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester.
26. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među slijedećim spojevima i njihovim farmaceutski prihvatljivim solima, solvatima i hidratima: (S)-4-(6-{6-[(2-metansulfonil-etil)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline 1-ciklopropil-etil ester; (2-fluoro-4-metansulfonil-fenil)-{4-[1-(5-izopropil-[1,2,4]oksadiazol-3-il)-piperidin-4-iloksi]-3-metoksi-piridin-2-il}-amin; 4-[6-(2-fluoro-4-metansulfonil-fenilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-[6-(4-cijano-2-fluoro-fenilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-hidroksi-etil)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{6-[6-(2-metansulfonil-etil)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-{2-[6-(2-metansulfonil-etil)-2-metil-piridin-3-ilamino]-3-metoksi-piridin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester; 4-[6-(6-dimetilkarbamoilmetil-2-metil-piridin-3-ilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; te 4-{6-[6-(2-hidroksi-etoksi)-2-metil-piridin-3-ilamino]-5-metoksi-pirimidin-4-iloksi}-piperidin-1-karboksilne kiseline izopropil ester.
27. Pripravak u skladu sa zahtjevom 1, naznačen time, da je spoj izabran među slijedećim spojem i njegovim farmaceutski prihvatljivim solima, solvatima i hidratima: 4-[6-(6-metansulfonil-2-metil-piridin-3-ilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester.
28. Pripravak u skladu s bilo kojim zahtjevom 1 do 27, naznačen time, da je navedeni inhibitor dipeptidil peptidaze IV izabran iz slijedeće skupine: valin-pirolidid, 3-(L-izoleucil)tiazolidin, 1-[2-[5-cijanopiridin-2-il)amino]etilamino]acetil-2-cijano-(S)-pirolidin (NVP-DPP728), 3(R)-amino-1-[3-(trifluorometil)-5,6,7,8-tetrahidro[1,2,4]triazolo[4,3-a]pirazin-7-il]-4-(2,4,5-trifluorofenil)butan-1-on (MK-0431), (1-[[3-hidroksi-1-adamantil)amino]acetil]-2-cijano-(S)-pirolidin (LAF237), (1S, 3S, 5S)-2-[2(S)-amino-2-(3-hidroksiadamantan-1-il)acetil]-2-azabiciklo[3.1.0]heksan-3-karbonitril (BMS-477118), te [1-[2(S)-amino-3-metilbutiril]pirolidin-2-(R)]boronska kiselina (PT-100).
29. Pripravak u skladu s bilo kojim zahtjevom 1 do 26, naznačen time, da navedeni inhibitor dipeptidil peptidaze IV je 3(R)-amino-1-[3-(trifluorometil)-5,6,7,8-tetrahidro[1,2,4]triazolo[4,3-a]pirazin-7-il]-4-(2,4,5-trifluorofenil)butan-1-on (MK-0431).
30. Pripravak u skladu s bilo kojim zahtjevom 1 do 26, naznačen time, da navedeni inhibitor dipeptidil peptidaze IV je (1-[[3-hidroksi-1-adamantil)amino]acetil]-2-cijano-(S)-pirolidin (LAF237).
31. Pripravak u skladu s bilo kojim zahtjevom 1 do 26, naznačen time, da navedeni inhibitor dipeptidil peptidaze IV je (1S, 3S, 5S)-2-[2(S)-amino-2-(3-hidroksiadamantan-1-il)acetil]-2-azabiciklo[3.1.0]heksan-3-karbonitril (BMS-477118).
32. Postupak izrade pripravka u skladu s bilo kojim zahtjevom 1 do 31, naznačen time, da navedeni postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV) i navedenog spoja.
33. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, naznačen time, da nadalje sadrži farmaceutski prihvatljivu podlogu.
34. Postupak izrade pripravka u skladu sa zahtjevom 33, naznačen time, da postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV), navedenog spoja i navedene farmaceutski prihvatljive podloge.
35. Pripravak u skladu sa zahtjevom 1, naznačen time, da: spoj je izabran među slijedećim spojem i njegovim farmaceutski prihvatljivim solima, solvatima i hidratima: 4-[6-(6-metansulfonil-2-metil-piridin-3-ilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; te navedeni inhibitor dipeptidil peptidaze IV je 3(R)-amino-1-[3-(trifluorometil)-5,6,7,8-tetrahidro[1,2,4]triazolo[4,3-a]pirazin-7-il]-4-(2,4,5-trifluorofenil)butan-1-on (MK-0431).
36. Postupak izrade pripravka u skladu sa zahtjevom 35, naznačen time, da navedeni postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV) i navedenog spoja.
37. Pripravak u skladu sa zahtjevom 35, naznačen time, da nadalje sadrži farmaceutski prihvatljivu podlogu.
38. Postupak izrade pripravka u skladu sa zahtjevom 37, naznačen time, da postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV), navedenog spoja i navedene farmaceutski prihvatljive podloge.
39. Postupak u skladu sa zahtjevom 38, naznačen time, da nadalje obuhvaća korak izrade jediničnog dozirnog oblika pripravka.
40. Pripravak u skladu sa zahtjevom 1, naznačen time, da: spoj je izabran među slijedećim spojem i njegovim farmaceutski prihvatljivim solima, solvatima i hidratima: 4-[6-(6-metansulfonil-2-metil-piridin-3-ilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; te navedeni inhibitor dipeptidil peptidaze IV je (1-[[3-hidroksi-1-adamantil)amino]acetil]-2-cijano-(S)-pirolidin (LAF237).
41. Postupak izrade pripravka u skladu sa zahtjevom 40, naznačen time, da postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV) i navedenog spoja.
42. Pripravak u skladu sa zahtjevom 40, naznačen time, da nadalje sadrži farmaceutski prihvatljivu podlogu.
43. Postupak izrade pripravka u skladu sa zahtjevom 42, naznačen time, da postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV), navedenog spoja i navedene farmaceutski prihvatljive podloge.
44. Postupak u skladu sa zahtjevom 43, naznačen time, da nadalje obuhvaća korak izrade jediničnog dozirnog oblika pripravka.
45. Pripravak u skladu sa zahtjevom 1, naznačen time, da: spoj je izabran među slijedećim spojem i njegovim farmaceutski prihvatljivim solima, solvatima i hidratima: 4-[6-(6-metansulfonil-2-metil-piridin-3-ilamino)-5-metoksi-pirimidin-4-iloksi]-piperidin-1-karboksilne kiseline izopropil ester; te navedeni inhibitor dipeptidil peptidaze IV je (1S, 3S, 5S)-2-[2(S)-amino-2-(3-hidroksiadamantan-1-il)acetil]-2-azabiciklo[3.1.0]heksan-3-karbonitril (BMS-477118).
46. Postupak izrade pripravka u skladu sa zahtjevom 45, naznačen time, da postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV) i navedenog spoja.
47. Pripravak u skladu sa zahtjevom 45, naznačen time, da nadalje sadrži farmaceutski prihvatljivu podlogu.
48. Postupak izrade pripravka u skladu sa zahtjevom 47, naznačen time, da postupak obuhvaća miješanje navedenog inhibitora dipeptidil peptidaze IV (DPP-IV), navedenog spoja i navedene farmaceutski prihvatljive podloge.
49. Postupak u skladu sa zahtjevom 48, naznačen time, da nadalje obuhvaća korak izrade jediničnog dozirnog oblika pripravka.
50. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačen time, da se koristi u postupku liječenja ljudskog ili životinjskog tijela terapijom.
51. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačen time, da se koristi u postupku liječenja metabolički-posredovanih poremećaja ljudskog ili životinjskog tijela terapijom.
52. Uporaba pripravka u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačena time, da se koristi u izradi lijeka za liječenje metabolički-posredovanih poremećaja.
53. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačen time, da se koristi u postupku liječenja dijabetesa tip I, dijabetesa tip II, neodgovarajuće tolerancije glukoze, inzulinske rezistencije, hiperglikemije, hiperlipidemije, hipertrigliceridemije, hiperholesterolemije, dislipidemije ili sindroma X.
54. Uporaba pripravka u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačena time, da se koristi u izradi lijeka za liječenje dijabetesa tip I, dijabetesa tip II, neodgovarajuće tolerancije glukoze, inzulinske rezistencije, hiperglikemije, hiperlipidemije, hipertrigliceridemije, hiperholesterolemije, dislipidemije ili sindroma X.
55. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačen time, da se koristi u postupku liječenja dijabetesa tip II ljudskog ili životinjskog tijela terapijom.
56. Uporaba pripravka u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačena time, da se koristi u izradi lijeka za liječenje dijabetesa tip II.
57. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačen time, da se koristi u postupku liječenja smanjenjem unošenja hrane kod pojedinca.
58. Uporaba pripravka u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačena time, da se koristi u izradi lijeka za uporabu u liječenju smanjenjem unošenja hrane kod pojedinca.
59. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačen time, da se koristi u postupku liječenja izazivanjem sitosti kod pojedinca.
60. Uporaba pripravka u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačena time, da se koristi u izradi lijeka za uporabu u liječenju izazivanjem sitosti kod pojedinca.
61. Pripravak u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačen time, da se koristi u postupku liječenja kontroliranja povećanja težine kod pojedinca.
62. Uporaba pripravka u skladu s bilo kojim zahtjevom 1 do 31, 33, 35, 37, 40, 42, 45 i 47, naznačena time, da se koristi u izradi lijeka za uporabu u liječenju kontroliranja ili smanjivanja povećanja težine kod pojedinca.
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