HRP20191298T1 - Arileteri i njihove uporabe - Google Patents

Arileteri i njihove uporabe Download PDF

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Publication number
HRP20191298T1
HRP20191298T1 HRP20191298TT HRP20191298T HRP20191298T1 HR P20191298 T1 HRP20191298 T1 HR P20191298T1 HR P20191298T T HRP20191298T T HR P20191298TT HR P20191298 T HRP20191298 T HR P20191298T HR P20191298 T1 HRP20191298 T1 HR P20191298T1
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HR
Croatia
Prior art keywords
compound according
unsubstituted
hydrogen
hydroxy
compound
Prior art date
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HRP20191298TT
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English (en)
Inventor
Darryl David Dixon
Jonas Grina
John A. Josey
James P. Rizzi
Stephen T. Schlachter
Eli M. Wallace
Bin Wang
Paul Wehn
Rui Xu
Hanbiao Yang
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Peloton Therapeutics, Inc.
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Application filed by Peloton Therapeutics, Inc. filed Critical Peloton Therapeutics, Inc.
Publication of HRP20191298T1 publication Critical patent/HRP20191298T1/hr

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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A61K31/09—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon having two or more such linkages
    • 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
    • A61K31/095—Sulfur, selenium, or tellurium compounds, e.g. thiols
    • A61K31/10—Sulfides; Sulfoxides; Sulfones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
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    • C07C205/13—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups
    • C07C205/20—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings
    • C07C205/21—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring
    • C07C205/22—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by hydroxy groups having nitro groups and hydroxy groups bound to carbon atoms of six-membered aromatic rings having nitro groups and hydroxy groups bound to carbon atoms of the same non-condensed six-membered aromatic ring having one nitro groups bound to the ring
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    • C07C311/22—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms
    • C07C311/29—Sulfonamides, the carbon skeleton of the acid part being further substituted by singly-bound oxygen atoms having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
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    • C07C317/32—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
    • C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
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    • C07C317/34—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring
    • C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
    • C07C317/40—Y being a hydrogen or a carbon atom
    • C—CHEMISTRY; METALLURGY
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    • C07C317/38—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton having sulfone or sulfoxide groups and amino groups bound to carbon atoms of six-membered aromatic rings being part of the same non-condensed ring or of a condensed ring system containing that ring with the nitrogen atom of at least one amino group being part of any of the groups, X being a hetero atom, Y being any atom, e.g. N-acylaminosulfones
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Claims (15)

1. Spoj, naznačen time, da je predstavljen formulom III: ili njegova farmaceutski prihvatljiva sol, gdje: n je 1, 2, 3 ili 4; R1 je fenil ili piridil, pri čemu je navedeni fenil ili piridil supstituiran s najmanje jednim supstituentom odabranim iz skupine koja se sastoji od halogena, C1-C4-alkila, C1-C4-alkoksi i cijano; R4 je cijano, fluoroalkil, sulfonamid, sulfinil, sulfonil ili sulfoksiminil; R5 je vodik, halogen ili nesupstituirani alkil; R8 je vodik, hidroksi, nesupstituirani alkilamino, nesupstituirani alkoksi ili amino; R9 je vodik, nesupstituirani alkil, nesupstituirani alkenil ili nesupstituirani alkinil; ili R8 i R9 zajedno tvore okso ili oksim; i svaki od R10 je neovisno odabran iz skupine koja se sastoji od vodika, fluora, klora, hidroksi i nesupstituiranog alkila; ili dva R10 i ugljikov(i) atom(i) na koje su oni priključeni, tvore 3-člani do 8-člani nesupstituirani cikloalkila ili nesupstituirani heterocikloalkil.
2. Spoj prema zahtjevu 1, naznačen time, da R9 je vodik.
3. Spoj prema zahtjevu 1, naznačen time, da R10 je fluor i n je 1, 2 ili 3.
4. Spoj prema zahtjevu 1, naznačen time, da R4 je cijano, fluoroalkil, sulfinil, sulfonamid, sulfonil ili sulfoksiminil; R5 je vodik; R8 je hidroksi ili amino; i R9 je vodik.
5. Spoj prema zahtjevu 1, naznačen time, da je predstavljen formulom IVa: ili njegova farmaceutski prihvatljiva sol.
6. Spoj prema zahtjevu 5, naznačen time, da je predstavljen formulom Va: ili njegova farmaceutski prihvatljiva sol, gdje: R4 je cijano, fluoroalkil, sulfonamid, sulfinil, sulfonil ili sulfoksiminil; i R8 je hidroksi, nesupstituirani alkilamino, nesupstituirani alkoksi ili amino.
7. Spoj prema bilo kojem od zahtjeva 1, 5 ili 6, naznačen time, da R8 je hidroksi ili amino.
8. Spoj prema zahtjevu 5 ili 6, naznačen time, da R4 je cijano, fluoroalkil, sulfonamid, sulfinil, sulfonil ili sulfoksiminil; R5 je vodik; i R8 je hidroksi ili amino.
9. Spoj prema zahtjevu 6, naznačen time, da enantiomerni višak navedenog spoja iznosi najmanje oko 80%.
10. Spoj prema zahtjevu 1, naznačen time, da spoj je (S)-3-((2,2-difluoro-1-hidroksi-7-(me3tilsulfonil)-2,3-dihidro-1H-inden-4-il)oksi)-5-fluorobenzonitril, koji je predstavljen formulom: ili njegova farmaceutski prihvatljiva sol.
11. Farmaceutski pripravak, naznačen time, da obuhvaća terapeutski djelotvornu količinu spoja ili njegove farmaceutski prihvatljive soli u skladu s bilo kojim od zahtjeva 1 do 10 i farmaceutski prihvatljiv nosač.
12. Spoj prema bilo kojem od zahtjeva 1 do 10, naznačen time, da se upotrebljava kao lijek za liječenje bolesti von Hippel-Lindau (VHL-sindrom).
13. Spoj prema bilo kojem od zahtjeva 1 do 10, naznačen time, da se upotrebljava kao lijek za liječenje hemangioblastoma, feokromocitoma, neuroendokrinskog tumora gušterače ili karcinoma bubrežnih stanica.
14. Spoj prema bilo kojem od zahtjeva 1 do 10, naznačen time, da se upotrebljava kao lijek za liječenje karcinoma bubrežnih stanica.
15. Spoj za uporabu prema zahtjevu 14, naznačen time, da se kod navedenog karcinoma bubrežnih stanica radi o karcinomu svijetlih stanica bubrežnih stanica.
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