ME02664B - Derivati premeštanja piridina u toku transfekcije inhibitora (ret) kinaze - Google Patents

Derivati premeštanja piridina u toku transfekcije inhibitora (ret) kinaze

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Publication number
ME02664B
ME02664B MEP-2017-60A MEP201760A ME02664B ME 02664 B ME02664 B ME 02664B ME P201760 A MEP201760 A ME P201760A ME 02664 B ME02664 B ME 02664B
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Montenegro
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alkyl
ethoxy
dihydropyridin
oxo
fluorophenyl
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MEP-2017-60A
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German (de)
English (en)
French (fr)
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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 Ip Dev Ltd
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Publication of ME02664B publication Critical patent/ME02664B/me

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • 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
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • 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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  • Animal Behavior & Ethology (AREA)
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  • General Chemical & Material Sciences (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pyridine Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Peptides Or Proteins (AREA)
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Claims (15)

1.Jedinjenje prema formuli (I): gde: R1 je vodonik, halogen, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, hidroksil, (C1-C6)alkoksi, halo(C1-C6)alkoksi, (C3-C6)cikloalkoksi, amino, ((C1-C6)alkil)amino-, ili ((C1-C6)alkil)((C1-C6)alkil)amino-; svaki R2 je nezavisno izabran iz grupe koju čine halogen, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, cijano, hidroksil, (C1-C6)alkoksi, halo(C1-C6)alkoksi, (C3-C6)cikloalkoksi, amino, ((C1-C6)alkil)amino-, i ((C1-C6)alkil)((C1-C6)alkil)amino-; R3 je fenil ili 5- ili 6-člani heteroaril, od kojih je svaki opciono supstituisan sa jednim ili tri supstituenta nezavisno izabrana od halogena, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, cijano, 5- ili 6-člani heteroaril, -OR4, i -CONR5R6; gde je pomenuti (C1-C6)alkil opciono supstitusian sa cijano, hidroksil, (C1-C4)alkoksi, halo(C1-C4)alkoksi, ili -NR5R6; i gde je pomenuti 5- ili 6-člani heteroaril substituent opciono supstituisan sa halogenom, (C1-C4)alkil, ili halo(C1-C4)alkil; R4 je vodonik, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, ili 4- do 6-člani heterocikloalkil; gde pomenuti (C1-C6)alkil je opciono supstituisan sa cijano, hidroksil, (C1-C4)alkoksi, halo(C1-C4)alkoksi, ili -NR5R6; i gde je pomenuti (C3-C6)cikloalkil opciono supstituisan sa jednim ili dva supstituenta nezavisno izabrana od (C1-C4)alkil, halo(C1-C4)alkil, hidroksil, hidroksi(C1-C4)alkil, (C1-C4)alkoksi, i halo(C1-C4)alkoksi; i gde je pomenuti 4- do 6-člani heterocikloalkil opciono supstituisan sa jednim ili dva supstituenta nezavisno izabrana između (C1-C4)alkil i halo(C1-C4)alkil; R5 i R6 su svaki nezavisno izabrani iz grupe koju čine vodonik, (C1-C4)alkil, i halo(C1-C4)alkil; ili R5 i R6 zajedno sa azotovim atomom za koji su vezani predstavljaju 5- ili 6- člani zasićeni prsten, opciono koji sadrži dodatni heteroatom izabran između kiseonika, azota i sumpora, gde pomenuti prsten je opciono supstituisan halogenom, (C1-C4)alkil, ili halo(C1-C4)alkil; i n je 0, 1, ili 2; ili njegova farmaceutski prihvatljiva so.
2.Jedinjenje ili njegova farmaceutski prihvatljiva so prema zahtevu 1 predstavljeno formulom (II): gde: X je N ili CR10; R1 je vodonik, halogen, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, hidroksil, (C1-C6)alkoksi, halo(C1-C6)alkoksi, (C3-C6)cikloalkoksi, amino, ((C1-C6)alkil)amino-, ili ((C1-C6)alkil)((C1-C6)alkil)amino-; svaki R2 je nezavisno izabran iz grupe koju čine halogen, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, cijano, hidroksil, (C1-C6)alkoksi, halo(C1-C6)alkoksi, (C3-C6)cikloalkoksi, amino, ((C1-C6)alkil)amino-, i ((C1-C6)alkil)((C1-C6)alkil)amino-; R4 je vodonik, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, ili 4- do 6-člani heterocikloalkil; gde pomenuti (C1-C6)alkil je opciono supstituisan sa cijano, hidroksil, (C1-C4)alkoksi, halo(C1-C4)alkoksi, ili-NR5R6; i gde pomenuti (C3-C6)cikloalkil je opciono supstituisan sa jednim ili dva supstituenta nezavisno izabrana između (C1-C4)alkil, halo(C1-C4)alkil, hidroksil, hidroksi(C1-C4)alkil, (C1-C4)alkoksi, i halo(C1-C4)alkoksi; i gde pomenuti 4- do 6-člani heterocikloalkil je opciono supstituisan sa jednim ili dva supstituenta nezavisno izabrana između (C1-C4)alkil i halo(C1-C4)alkil; R5 i R6 su svaki nazavisno izabrani iz grupe koju čine vodonik, (C1-C4)alkil, i halo(C1-C4)alkil; ili R5 i R6 uzeti zajedno sa azotovim atomom za koji su vezani predstavljaju 5- ili 6- člani zasićeni prsten, koji opciono sadrži dodatni heteroatom izabran između kiseonika, azota i sumpora, gde je pomenuti prsten opciono supstituisan sa halogenom, (C1-C4)alkil, ili halo(C1-C4)alkil; R7 je vodonik, halogen ili (C1-C4)alkoksi; R8 je vodonik, halogen, (C1-C6)alkil, halo(C1-C6)alkil, (C3-C6)cikloalkil, cijano, 5- ili 6-člani heteroaril, -OR4, ili -CONR5R6; gde je pomenuti (C1-C6)alkil opciono supstituisan sa cijano, hidroksil, (C1-C4)alkoksi, halo(C1-C4)alkoksi, ili -NR5R6; i gde je pomenuti 5- ili 6-člani heteroaril opciono supstituisan sa halogenom, (C1-C4)alkil, ili halo(C1-C4)alkil; R9 je vodonik, halogen ili halo(C1-C4)alkil; R10 je vodonik, halogen, halo(C1-C4)alkil, ili 5- ili 6-člani heteroaril, gde je pomenuti 5- ili 6-člani heteroaril opciono supstituisan sa halogenom, (C1-C4)alkil, ili halo(C1-C4)alkil; i n je 0, 1, ili 2; uz uslov da kad je X CR10 bar jedan od R7, R8, R9, i R10 je vodonik.
3.Jedinjenje ili njegova farmaceutski prihvatljiva so prema zahtevu 2, gde je R7 vodonik ili fluor.
4.Jedinjenje ili njegova farmaceutski prihvatljiva so prema zahtevu 2 ili zahtevu 3, gde je R8 vodonik, fluor, hlor, (C1-C6)alkil, halo(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; gde je pomenuti (C1-C6)alkil opciono supstituisan sa cijano, hidroksil, (C1-C4)alkoksi, amino, ((C1-C4)alkil)amino-, ili ((C1-C4)alkil)((C1-C4)alkil)amino-.
5.Jedinjenje ili njegova farmaceutski prihvatljiva so prema zahtevu 4, gde je R8 vodonik ili (C1-C6)alkil; gde je pomenuti (C1-C6)alkil opciono supstituisan sa cijano, hidroksil, (C1-C4)alkoksi, amino, ((C1-C4)alkil)amino-, ili ((C1-C4)alkil)((C1-C4)alkil)amino-.
6.Jedinjenje ili njegova farmaceutski prihvatljiva so prema bilo kom od zahteva 2-5, gde je R9 trifluorometil.
7.Jedinjenje ili njegova farmaceutski prihvatljiva so prema bilo kom od zahteva 2-6, gde je X CH.
8.Jedinjenje ili njegova farmaceutski prihvatljiva so prema bilo kom od zahteva 1-7, gde je R1 (C1-C4)alkoksi.
9.Jedinjenje ili njegova farmaceutski prihvatljiva so prema bilo kom od zahteva 1-8, gde je n 1 ili 2 i svaki R2 je nezavisno halogen.
10.Jedinjenje prema zahtevu 1 koje je: 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(6-(2-hidroksipropan-2-il)-5-(trifluorometil)piridin-3-il)acetamid; N-(6-etoksi-5-(trifluorometil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)acetamid; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluorometil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2,3-difluorofenil)-N-(4-(2-hidroksietoksi)-3-(trifluorometil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluorometil)fenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-3-fluorofenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluorometil)fenil)acetamid; N-(4-cijano-3-(trifluorometil)fenil)-2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-3-fluorofenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2,6-difluorofenil)-N-(4-(2-hidroksietoksi)-3-(trifluorometil)fenil)acetamid; N-(4-cijano-3-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)acetamid; N-(6-(2-(dimetilamino)etoksi)-5-(trifluorometil)piridin-3-il)-2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)acetamid; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(4-metil-1H-imidazol-1-il)-5-(trifluorometil)fenil)metil; N-(6-(2-cijanopropan-2-il)-5-(trifluorometil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(4-(2-hidroksietoksi)-3-(trifluorometil)fenil)metil; N-(6-(cijanometil)-5-(trifluorometil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; N-(6-(1-cijanoetil)-5-(trifluorometil)piridin-3-il)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; N-(4-hloro-3-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; N-(4-((dimetilamino)metil)-3-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; N-(3,4-dihlorofenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(5-(1,1,1-trifluoro-2-metilpropan-2-il)izoksazol-3-il)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(4-(2-hidroksietoksi)-3-(trifluorometil)fenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(4-((4-etilpiperazin-1-il)metil)-3-(trifluorometil)fenil)metil; N-(2,5-difluorofenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; 4-(2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)acetamido)-2-(trifluorometil)benzamid; N-(2,4-difluoro-5-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; N-(3,5-bis(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(2-fluoro-5-(trifluorometil)fenil)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(1,1,1-trifluoro-2-metilpropan-2-il)izoksazol-5-il)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(1,1,1-trifluoro-2-metilpropan-2-il)izoksazol-5-il)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(5-metil-1,3,4-oksadiazol-2-il)-5-(trifluorometil)fenil)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(5-(1,1,1-trifluoro-2-metilpropan-2-il)izoksazol-3-il)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(6-(1-hidroksi-2-metilpropan-2-il)-5-(trifluorometil)piridin-3-il)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-3-fluorofenil)-N-(4-(3-hidroksi-2,2-dimetilpropil)-3-(trifluorometil)fenil)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(trifluorometil)fenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(4-metil-1H-pirazol-1-il)-5-(trifluorometil)fenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(3-metil-1H-pirazol-1-il)-5-(trifluorometil)fenil)metil; N-(3-(1H-pirazol-4-il)-5-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(6-(1,1,1-trifluoro-2-metilpropan-2-il)piridin-3-il)metil; N-(4-cijano-3-(trifluorometil)fenil)-2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(2-morfolinoetoksi)-5-(trifluorometil)fenil)metil; 2-(4-(4-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(1,1,1-trifluoro-2-metilpropan-2-il)izoksazol-5-il)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(1-metil-3-(1,1,1-trifluoro-2-metilpropan-2-il)-1H-pirazol-5-il)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(1,1,1-trifluoro-2-metilpropan-2-il)-1H-pirazol-5-il)metil; N-(4-(2,2-difluoro-3-hidroksipropil)-3-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; N-(3-(2H-tetrazol-5-il)-5-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; 2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)-N-(3-(1-metil-1H-pyrazol-4-il)-5-(trifluorometil) fenil)metil; ili N-(3-(2-(dimetilamino)etoksi)-5-(trifluorometil)fenil)-2-(4-(5-etoksi-6-okso-1,6-dihidropiridin-3-il)-2-fluorofenil)metil; ili njegova farmaceutski prihvatljiva so.
11.Jedinjenje prema zahtevu 1, koje je: ili njegova farmaceutski prihvatljiva so.
12.Jedinjenje prema zahtevu 11, gde je jedinjenje slobodna baza.
13.Farmaceutska kompozicija koja sadrži jedinjenje ili njegovu farmaceutski prihvatljivu so prema bilo kom od zahteva 1-12 i farmaceutski prihvatljiv ekscipijent.
14.Jedinjenje ili njegova farmaceutski prihvatljiva so prema bilo kom od zahteva 1-12 za upotrebu u terapiji.
15. Jedinjenje ili njegova farmaceutski prihvatljiva so prema bilo kom od zahteva 1-12 za upotrebu u lečenju sindroma nervoznih creva.
MEP-2017-60A 2013-03-15 2014-03-14 Derivati premeštanja piridina u toku transfekcije inhibitora (ret) kinaze ME02664B (me)

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