HRP20170363T1 - Derivati piridina kao inhibitori kinaze pregrađene prilikom transfekcije (ret) - Google Patents

Derivati piridina kao inhibitori kinaze pregrađene prilikom transfekcije (ret) Download PDF

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HRP20170363T1
HRP20170363T1 HRP20170363TT HRP20170363T HRP20170363T1 HR P20170363 T1 HRP20170363 T1 HR P20170363T1 HR P20170363T T HRP20170363T T HR P20170363TT HR P20170363 T HRP20170363 T HR P20170363T HR P20170363 T1 HRP20170363 T1 HR P20170363T1
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alkyl
ethoxy
dihydropyridin
oxo
acetamide
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Hilary Schenck Eidam
Michael P. Demartino
Zhen Gong
Amy Huiping GUAN
Kaushik Raha
Chengde Wu
Haiying Yang
Haiyu Yu
Zhiliu Zhang
Mui Cheung
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Glaxosmithkline Intellectual Property Development Limited
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/06—Anti-spasmodics, e.g. drugs for colics, esophagic dyskinesia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/69—Two or more oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

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  • Pyridine Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Claims (15)

1. Spoj u skladu s Formulom (I): [image] , naznačen time što: R1 je vodik, halogen, (C1-C6)alkil, halogen(C1-C6)alkil, (C3-C6)ciklkoalkil, hidroksil, (C1-C6)alkoksi, halogen(C1-C6)alkoksi, (C3-C6)ciklkoalkoksi, amino, ((C1-C6)alkil)amino- ili ((C1-C6)alkil)((C1-C6)alkil)amino-; svakog R2 se neovisno bira iz skupine koju čine halogen, (C1-C6)alkil, halogen(C1-C6)alkil, (C3-C6)ciklkoalkil, cijano, hidroksil, (C1-C6)alkoksi, halogen(C1-C6)alkoksi, (C3-C6)ciklkoalkoksi, amino, ((C1-C6)alkil)amino- i ((C1-C6)alkil)((C1-C6)alkil)amino-; R3 je fenil ili 5- ili 6-eročlani heteroaril, od kojih svaki može biti supstituiran s jednim do tri supstituenta, koje se neovisno bira između halogena, (C1-C6)alkila, halogen(C1-C6)alkila, (C3-C6)ciklkoalkila, cijano, 5- ili 6-eročlanog heteroarila, -OR4 i -CONR5R6; gdje navedeni (C1-C6)alkil može biti supstituiran s cijano, hidroksilom, (C1-C4)alkoksi, halogen(C1-C4)alkoksi ili -NR5R6; i gdje navedeni 5- ili 6-eročlani heteroaril supstituent može biti supstituiran s halogenom, (C1-C4)alkilom ili halogen(C1-C4)alkilom; R4 je vodik, (C1-C6)alkil, halogen(C1-C6)alkil, (C3-C6)ciklkoalkil ili 4- do 6-eročlani heterociklkoalkil; gdje navedeni (C1-C6)alkil može biti supstituiran s cijano, hidroksilom, (C1-C4)alkoksi, halogen(C1-C4)alkoksi ili -NR5R6; i gdje navedeni (C3-C6)ciklkoalkil može biti supstituiran s jednim ili dva supstituenta, koje se neovisno bira između (C1-C4)alkila, halogen(C1-C4)alkila, hidroksila, hidroksi(C1-C4)alkila, (C1-C4)alkoksi i halogen(C1-C4)alkoksi; i gdje navedeni 4- do 6-eročlani heterociklkoalkil može biti supstituiran s jednim ili dva supstituenta, koje se neovisno bira između (C1-C4)alkila i halogen(C1-C4)alkila; svakog od R5 i R6 se neovisno bira iz skupine koju čine vodik, (C1-C4)alkil i halogen(C1-C4)alkil; ili R5 i R6, uzeti zajedno s dušikom na kojeg su vezani, predstavljaju 5- ili 6-eročlani zasićeni prsten, koji može sadržavati dodatni heteroatom, kojeg se bira između kisika, dušika i sumpora, gdje navedeni prsten može biti supstituiran s halogenom, (C1-C4)alkilom ili halogen(C1-C4)alkilom; i n je 0, 1 ili 2; ili njegova farmaceutski prihvatljiva sol.
2. Spoj, ili farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 1, prikazan Formulom (II): [image] , naznačen time što: X je N ili CR10; R1 je vodik, halogen, (C1-C6)alkil, halogen(C1-C6)alkil, (C3-C6)ciklkoalkil, hidroksil, (C1-C6)alkoksi, halogen(C1-C6)alkoksi, (C3-C6)ciklkoalkoksi, amino, ((C1-C6)alkil)amino- ili ((C1-C6)alkil)((C1-C6)alkil)amino-; svakog R2 se neovisno bira iz skupine koju čine halogen, (C1-C6)alkil, halogen(C1-C6)alkil, (C3-C6)ciklkoalkil, cijano, hidroksil, (C1-C6)alkoksi, halogen(C1-C6)alkoksi, (C3-C6)ciklkoalkoksi, amino, ((C1-C6)alkil)amino- i ((C1-C6)alkil)((C1-C6)alkil)amino-; R4 je vodik, (C1-C6)alkil, halogen(C1-C6)alkil, (C3-C6)ciklkoalkil ili 4- do 6-eročlani heterociklkoalkil; gdje navedeni (C1-C6)alkil može biti supstituiran s cijano, hidroksilom, (C1-C4)alkoksi, halogen(C1-C4)alkoksi ili -NR5R6; i gdje navedeni (C3-C6)ciklkoalkil može biti supstituiran s jednim ili dva supstituenta, koje se neovisno bira između (C1-C4)alkila, halogen(C1-C4)alkila, hidroksila, hidroksi(C1-C4)alkila, (C1-C4)alkoksi i halogen(C1-C4)alkoksi; i gdje navedeni 4- do 6-eročlani heterociklkoalkil može biti supstituiran s jednim ili dva supstituenta, koje se neovisno bira između (C1-C4)alkila i halogen(C1-C4)alkila; svakog od R5 i R6 se neovisno bira iz skupine koju čine vodik, (C1-C4)alkil i halogen(C1-C4)alkil; ili R5 i R6, uzeti zajedno s dušikom na kojeg su vezani, predstavljaju 5- ili 6-eročlani zasićeni prsten, koji može sadržavati dodatni heteroatom, kojeg se bira između kisika, dušika i sumpora, gdje navedeni prsten može biti supstituiran s halogenom, (C1-C4)alkilom ili halogen(C1-C4)alkilom; R7 je vodik, halogen ili (C1-C4)alkoksi; R8 je vodik, halogen, (C1-C6)alkil, halogen(C1-C6)alkil, (C3-C6)ciklkoalkil, cijano, 5- ili 6-eročlani heteroaril, -OR4 ili -CONR5R6; gdje navedeni (C1-C6)alkil može biti supstituiran s cijano, hidroksilom, (C1-C4)alkoksi, halogen(C1-C4)alkoksi ili -NR5R6; i gdje navedeni 5- ili 6-eročlani heteroaril može biti supstituiran s halogenom, (C1-C4)alkilom ili halogen(C1-C4)alkilom; R9 je vodik, halogen ili halogen(C1-C4)alkil; R10 je vodik, halogen, halogen(C1-C4)alkil ili 5- ili 6-eročlani heteroaril, gdje navedeni 5- ili 6-eročlani heteroaril može biti supstituiran s halogenom, (C1-C4)alkilom ili halogen(C1-C4)alkilom; i n je 0, 1 ili 2; uz uvjet da kada je X CR10, najmanje jedan od R7, R8, R9 i R10 je vodik.
3. Spoj, ili farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 2, naznačen time što je R7 vodik ili fluor.
4. Spoj, ili farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 2 ili patentnim zahtjevom 3, naznačen time što je R8 vodik, fluor, klor, (C1-C6)alkil, halogen(C1-C4)alkil, cijano, (C1-C4)alkoksi, hidroksi(C2-C4)alkoksi-, (C1-C4)alkoksi(C2-C4)alkoksi-, amino(C2-C4)alkoksi-, ((C1-C4)alkil)amino(C2-C4)alkoksi-, ((C1-C4)alkil)((C1-C4)alkil)amino(C2-C4)alkoksi- ili -CONH2; gdje navedeni (C1-C6)alkil može biti supstituiran s cijano, hidroksilom, (C1-C4)alkoksi, amino, ((C1-C4)alkil)amino- ili ((C1-C4)alkil)((C1-C4)alkil)amino-.
5. Spoj, ili farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 4, naznačen time što je R8 vodik ili (C1-C6)alkil; gdje navedeni (C1-C6)alkil može biti supstituiran s cijano, hidroksilom, (C1-C4)alkoksi, amino, ((C1-C4)alkil)amino- ili ((C1-C4)alkil)((C1-C4)alkil)amino-.
6. Spoj, ili farmaceutski prihvatljiva sol, u skladu s bilo kojim od patentnih zahtjeva 2-5, naznačen time što je R9 trifluormetil.
7. Spoj, ili farmaceutski prihvatljiva sol, u skladu s bilo kojim od patentnih zahtjeva 2-6, naznačen time što je X CH.
8. Spoj, ili farmaceutski prihvatljiva sol, u skladu s bilo kojim od patentnih zahtjeva 1-7, naznačen time što je R1 (C1-C4)alkoksi.
9. Spoj, ili farmaceutski prihvatljiva sol, u skladu s bilo kojim od patentnih zahtjeva 1-8, naznačen time što je n 1 ili 2, a svaki R2 je neovisno halogen.
10. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je: 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(6-(2-hidroksipropan-2-il)-5-(trifluormetil)piridin-3-il)acetamid; N-(6-etoksi-5-(trifluormetil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluormetil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2,3-difluorfenil)-N-(4-(2-hidroksietoksi)-3-(trifluormetil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluormetil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-3-fluorfenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluormetil)fenil)acetamid; N-(4-cijano-3-(trifluormetil)fenil)-2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-3-fluorfenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2,6-difluorfenil)-N-(4-(2-hidroksietoksi)-3-(trifluormetil)fenil)acetamid; N-(4-cijano-3-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; N-(6-(2-(dimetilamino)etoksi)-5-(trifluormetil)piridin-3-il)-2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(4-metil-1H-imidazol-1-il)-5-(trifluormetil)fenil)acetamid; N-(6-(2-cijanopropan-2-il)-5-(trifluormetil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(4-(2-hidroksietoksi)-3-(trifluormetil)fenil)acetamid; N-(6-(cijanometil)-5-(trifluormetil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; N-(6-(1-cijanoetil)-5-(trifluormetil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; N-(4-klor-3-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; N-(4-((dimetilamino)metil)-3-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; N-(3,4-diklorfenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(5-(1,1,1-trifluor-2-metilpropan-2-il)izoksazol-3-il)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(4-(2-hidroksietoksi)-3-(trifluormetil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(4-((4-etilpiperazin-1-il)metil)-3-(trifluormetil)fenil)acetamid; N-(2,5-difluorfenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 4-(2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamido)-2-(trifluormetil)benzamid; N-(2,4-difluor-5-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; N-(3,5-bis(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(2-fluor-5-(trifluormetil)fenil)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(1,1,1-trifluor-2-metilpropan-2-il)izoksazol-5-il)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(1,1,1-trifluor-2-metilpropan-2-il)izoksazol-5-il)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(5-metil-1,3,4-oksadiazol-2-il)-5-(trifluormetil)fenil)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(5-(1,1,1-trifluor-2-metilpropan-2-il)izoksazol-3-il)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(6-(1-hidroksi-2-metilpropan-2-il)-5-(trifluormetil)piridin-3-il)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-3-fluorfenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluormetil)fenil)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(trifluormetil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(4-metil-1H-pirazol-1-il)-5-(trifluormetil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(3-metil-1H-pirazol-1-il)-5-(trifluormetil)fenil)acetamid; N-(3-(1H-pirazol-4-il)-5-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(6-(1,1,1-trifluor-2-metilpropan-2-il)piridin-3-il)acetamid; N-(4-cijano-3-(trifluormetil)fenil)-2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(2-morfolinoetoksi)-5-(trifluormetil)fenil)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(1,1,1-trifluor-2-metilpropan-2-il)izoksazol-5-il)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(1-metil-3-(1,1,1-trifluor-2-metilpropan-2-il)-1H-pirazol-5-il)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(1,1,1-trifluor-2-metilpropan-2-il)-1H-pirazol-5-il)acetamid; N-(4-(2,2-difluor-3-hidroksipropil)-3-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; N-(3-(2H-tetrazol-5-il)-5-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)-N-(3-(1-metil-1H-pirazol-4-il)-5-(trifluormetil)fenil)acetamid; ili N-(3-(2-(dimetilamino)etoksi)-5-(trifluormetil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorfenil)acetamid; ili njihove farmaceutski prihvatljive soli.
11. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je: [image] , ili njegova farmaceutski prihvatljiva sol.
12. Spoj u skladu s patentnim zahtjevom 11, naznačen time što je spoj slobodna baza.
13. Farmaceutski pripravak, naznačen time što sadrži spoj, ili farmaceutski prihvatljivu sol, u skladu s bilo kojim od patentnih zahtjeva 1-12, kao i farmaceutski prihvatljivu pomoćnu tvar.
14. Spoj, ili farmaceutski prihvatljiva sol, u skladu s bilo kojim od patentnih zahtjeva 1-12, naznačen time što je namijenjen upotrebi u terapiji.
15. Spoj, ili farmaceutski prihvatljiva sol, u skladu s bilo kojim od patentnih zahtjeva 1-12, naznačen time što je namijenjen upotrebi u liječenju sindroma iritabilnih crijeva.
HRP20170363TT 2013-03-15 2017-03-06 Derivati piridina kao inhibitori kinaze pregrađene prilikom transfekcije (ret) HRP20170363T1 (hr)

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