HRP20171565T1 - C17-heteroaril derivati oleanolne kiseline i postupci njihove uporabe - Google Patents

C17-heteroaril derivati oleanolne kiseline i postupci njihove uporabe Download PDF

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Publication number
HRP20171565T1
HRP20171565T1 HRP20171565TT HRP20171565T HRP20171565T1 HR P20171565 T1 HRP20171565 T1 HR P20171565T1 HR P20171565T T HRP20171565T T HR P20171565TT HR P20171565 T HRP20171565 T HR P20171565T HR P20171565 T1 HRP20171565 T1 HR P20171565T1
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aromatic
ring
compound according
atoms
alkyl
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HRP20171565TT
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Xin Jiang
Christopher F. Bender
Melean Visnick
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Reata Pharmaceuticals, Inc.
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Publication of HRP20171565T1 publication Critical patent/HRP20171565T1/hr

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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D271/00Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/101,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07JSTEROIDS
    • C07J63/00Steroids in which the cyclopenta(a)hydrophenanthrene skeleton has been modified by expansion of only one ring by one or two atoms
    • C07J63/008Expansion of ring D by one atom, e.g. D homo steroids
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • A61P39/06Free radical scavengers or antioxidants
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D271/00Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/061,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Toxicology (AREA)
  • Biochemistry (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Epidemiology (AREA)
  • Lubricants (AREA)
  • Steroid Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Claims (15)

1. Spoj s formulom: [image] naznačen time da: n je 0-3; Ar je heteroarendiil(C≤8) ili njegova supstituirana verzija; i Y je: vodik, hidroksi, halo, amino, ili cijano ili -NCO; ili alkil(C≤8), cikloalkil(C≤8), alkenil(C≤8), alkinil(C≤8), aril(C≤12), aralkil(C≤12), heteroaril(C≤8), heterocikloalkil(C≤12), acil(C≤12), alkoksi(C≤8), ariloksi(C≤12), aciloksi(C≤8), alkilamino(C≤8), dialkilamino(C≤8), arilamino(C≤8), aralkilamino(C≤8), alkiltio(C≤8), aciltio(C≤8), alkilsulfonilamino(C≤8), ili supstituirane verzije bilo koje od navedenih skupina; ili njihova farmaceutski prihvatljiva sol; i pri čemu u supstituiranim verzijama alkil(C≤8), cikloalkil(C≤8), alkenil(C≤8), alkinil(C≤8), aril(C≤8), aralkil(C≤12), heteroaril(C≤8), acil(C≤12), alkoksi(C≤8), ariloksi(C≤12), aciloksi(C≤8), alkilamino(C≤8), dialkilamino(C≤8), arilamino(C≤8), aralkilamino(C≤8), alkiltio(C≤8), aciltio(C≤8), alkilsulfonilamino(C≤8) jedan ili više vodikovih atoma je neovisno zamijenjen sa -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, ili -S(O)2NH2 u supstituiranoj verziji heterocikloalkila(C≤8), jedan ili više vodikovih atoma je neovisno zamijenjen sa -OH, -F, -Cl, -Br, -I, -NH2, -NO2, -CO2H, -CO2CH3, -CN, -SH, -OCH3, -OCH2CH3, -C(O)CH3, -NHCH3, -NHCH2CH3, -N(CH3)2, -C(O)NH2, -OC(O)CH3, -S(O)2NH2 ili -C(O)OC(CH3)3; izraz "aril" odnosi se na jednovalentnu aromatsku skupinu s aromatskim ugljikovim atomom as kao točkom spajanja koja tvori dio jedne ili više šestero-članih aromatskih prstenskih struktura, pri čemu atomi u prstenu su svi ugljik, te pri čemu, ako je prisutan više od jednog prstena, prstenovi mogu biti kondenzirani ili nekondenzirani, i pri čemu jedna ili više skupina alkil ili aralkil može biti spojena na prvi aromatski prsten ili bilo koji prisutan dodatni aromatski prsten, ako to dozvoljava ograničenje broja ugljika; izraz "heteroaril" odnosi se na jednovalentnu aromatsku skupinu s aromatskim ugljikovim atomom ili dušikovim atomom kao točkom spajanja, navedeni ugljikov atom ili dušikov atom tvori dio jedne ili više aromatskih prstenskih struktura pri čemu barem jedan od prstenskih atoma je dušik, kisik ili sumpor, pri čemu heteroarilna skupina ne sadrži druge atome osim ugljika, vodika, aromatskog dušika, aromatskog kisika i aromatskog sumpora, pri čemu ako je prisutan više od jednog prstena, prstenovi mogu biti kondenzirani ili nekondenzirani, i pri čemu jedna ili više skupina alkil, aril, i/ili aralkil može biti spojena na aromatski prsten ili aromatski prstenski sustav, ako to dozvoljava ograničenje broja ugljika; izraz "heteroarendiil" odnosi se na dvovalentnu aromatsku skupinu, sa dva aromatska ugljikova atoma, dva aromatska dušikova atoma, ili jedan aromatski ugljikov atom i jedan aromatski dušikov atom kao dvije točke spajanja, navedeni atomi tvore dio jedne ili više aromatskih prstenskih struktura pri čemu je barem jedan od atoma u prstenu dušik, kisik ili sumpor, pri čemu dvovalentna skupina ne sadrži druge atome osim ugljika, vodika, aromatskog dušika, aromatskog kisika i aromatskog sumpora, pri čemu, ako je prisutan više od jedan prsten, prstenovi mogu biti kondenzirani ili nekondenzirani, pri čemu nekondenzirani prstenovi mogu biti povezani preko jednog ili više od slijedećeg: kovalentne veze, alkendiila, ili alkendiilnih skupina, ako to dozvoljava ograničenje broja ugljika, i pri čemu jedna ili više skupina alkil, aril, i/ili aralkil može biti spojena na aromatski prsten ili aromatski prstenski sustav, ako to dozvoljava ograničenje broja ugljika; izraz "heterocikloalkil" odnosi se na jednovalentnu ne-aromatsku skupinu s ugljikovim atomom ili dušikovim atomom kao točkom spajanja, navedeni ugljikov atom ili dušikov atom tvore dio jedne ili više ne-aromatskih prstenastih struktura pri čemu barem jedan od atoma prstena je dušik, kisik ili sumpor, pri čemu heterocikloalkilna skupina ne sadrži atome osim ugljika, vodika, dušika, kisika i sumpora, pri čemu, ako je prisutan više od jednog prstena, prstenovi mogu biti kondenzirani ili nekondenzirani, pri čemu, jedna ili više alkilnih skupina može biti spojena na prsten ili prstenski sustav, ako to dozvoljava ograničenje broja ugljika, te pri čemu jedna ili više dvostrukih veza može biti prisutna u prstenu ili prstenskom sustavu, pod uvjetom da nastala skupina ostaje ne-aromatska; izraz "acil" odnosi se na skupinu -C(O)R, u kojoj R je vodik, alkil, aril, aralkil ili heteroaril; i izraz "dialkilamino" odnosi se na skupinu -NRR', u kojoj R i R' mogu biti iste ili različite alkilne skupine, ili R i R' mogu se uzeti zajedno da predstavljaju alkandiil.
2. Spoj prema zahtjevu 1, naznačen time da Y je -H.
3. Spoj prema zahtjevu 1, naznačen time da Y je alkil(C≤4) ili cikloalkil(C≤4).
4. Spoj prema zahtjevu 3, naznačen time da Y je metil, n-propil, izopropil ili ciklopropil.
5. Spoj prema zahtjevu 1, naznačen time da Y je supstituirani alkil(C≤4) ili supstituirani cikloalkil(C≤4).
6. Spoj prema zahtjevu 5, naznačen time da Y je metoksimetil.
7. Spoj prema bilo kojem od zahtjeva 1-6, naznačen time da Ar je [image] ili [image]
8. Spoj prema bilo kojem od zahtjeva 1-7, naznačen time da n = 0.
9. Spoj prema bilo kojem od zahtjeva 1-7, naznačen time da n = 1.
10. Spoj prema zahtjevu 1, naznačen time da je nadalje definiran kao: [image] [image] [image] ili [image] ili njihova farmaceutski prihvatljiva sol.
11. Spoj prema zahtjevu 1, naznačen time da je nadalje definiran kao: [image] ili njihova farmaceutski prihvatljiva sol.
12. Spoj prema zahtjevu 1, naznačen time da je nadalje definiran kao: [image] ili njegova farmaceutski prihvatljiva sol.
13. Farmaceutski pripravak naznačen time da sadrži: a) spoj prema bilo kojem od zahtjeva 1-12; i b) ekscipijent.
14. Spoj prema bilo kojem od zahtjeva 1-12 naznačen time da je za uporabu kao lijek.
15. Spoj za uporabu prema zahtjevu 14, naznačen time da lijek je za tretman pacijenta kod upale i/ili oksidacijskog stresa.
HRP20171565TT 2012-09-10 2017-10-16 C17-heteroaril derivati oleanolne kiseline i postupci njihove uporabe HRP20171565T1 (hr)

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US201261699199P 2012-09-10 2012-09-10
PCT/US2013/059015 WO2014040056A1 (en) 2012-09-10 2013-09-10 C17-heteroaryl derivatives of oleanolic acid and methods of use thereof
EP13767175.6A EP2892911B1 (en) 2012-09-10 2013-09-10 C17-heteroaryl derivatives of oleanolic acid and methods of use thereof

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US (1) US20140088163A1 (hr)
EP (1) EP2892911B1 (hr)
JP (1) JP6272870B2 (hr)
KR (1) KR102237364B1 (hr)
CN (1) CN104768965B (hr)
AU (1) AU2013312102B2 (hr)
BR (1) BR112015005200B1 (hr)
CA (1) CA2882417C (hr)
CY (1) CY1119762T1 (hr)
DK (1) DK2892911T3 (hr)
EA (1) EA029069B1 (hr)
ES (1) ES2644615T3 (hr)
HK (1) HK1211295A1 (hr)
HR (1) HRP20171565T1 (hr)
HU (1) HUE036797T2 (hr)
IL (1) IL237638B (hr)
IN (1) IN2015DN01547A (hr)
LT (1) LT2892911T (hr)
ME (1) ME02911B (hr)
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NZ (1) NZ705213A (hr)
PL (1) PL2892911T3 (hr)
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WO (1) WO2014040056A1 (hr)
ZA (1) ZA201501203B (hr)

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JP6272870B2 (ja) 2018-01-31
US20140088163A1 (en) 2014-03-27
EP2892911B1 (en) 2017-08-30
BR112015005200A2 (hr) 2017-08-15
AU2013312102B2 (en) 2018-03-08
PL2892911T3 (pl) 2018-03-30
IN2015DN01547A (hr) 2015-07-03
EA201590539A1 (ru) 2015-08-31
ZA201501203B (en) 2021-08-25
ME02911B (me) 2018-10-20
NZ705213A (en) 2018-07-27
MX2015003078A (es) 2015-07-14
PT2892911T (pt) 2017-11-02
IL237638B (en) 2020-04-30
CN104768965B (zh) 2018-05-11
CA2882417C (en) 2021-04-20
JP2015529227A (ja) 2015-10-05
RS56563B1 (sr) 2018-02-28
WO2014040056A1 (en) 2014-03-13
HK1211295A1 (en) 2016-05-20
LT2892911T (lt) 2017-11-10
HUE036797T2 (hu) 2018-07-30
ES2644615T3 (es) 2017-11-29
CY1119762T1 (el) 2018-06-27
KR20150053982A (ko) 2015-05-19
BR112015005200B1 (pt) 2022-07-05
CN104768965A (zh) 2015-07-08
MX366954B (es) 2019-07-31
CA2882417A1 (en) 2014-03-13
DK2892911T3 (en) 2017-10-23
KR102237364B1 (ko) 2021-04-06
IL237638A0 (en) 2015-04-30
AU2013312102A1 (en) 2015-03-12
EP2892911A1 (en) 2015-07-15
SI2892911T1 (sl) 2017-12-29
EA029069B1 (ru) 2018-02-28

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