HRP20161196T1 - Modulatori jetrenog receptora x - Google Patents

Modulatori jetrenog receptora x Download PDF

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HRP20161196T1
HRP20161196T1 HRP20161196TT HRP20161196T HRP20161196T1 HR P20161196 T1 HRP20161196 T1 HR P20161196T1 HR P20161196T T HRP20161196T T HR P20161196TT HR P20161196 T HRP20161196 T HR P20161196T HR P20161196 T1 HRP20161196 T1 HR P20161196T1
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alkyl
nrc
halogen
haloalkyl
compound according
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HRP20161196TT
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Chengguo DONG
Yi Fan
Katerina Leftheris
Stephen LOTESTA
Suresh B. Singh
Colin Tice
Wei Zhao
Yajun Zheng
Linghang Zhuang
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Vitae Pharmaceuticals, Inc.
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Publication of HRP20161196T1 publication Critical patent/HRP20161196T1/hr

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Claims (15)

1. Spoj prikazan sljedećom strukturnom formulom: [image] ; ili njegova farmaceutski prihvatljiva sol, naznačen time što: X je N ili CRc; R1 je alkil ili -NRaRb; R2 je H; halogen; -CN; -NRC(O)R; -C(O)OR; -C(O)NRaRb; monociklički heteroaromat, koji može biti supstituiran s jednom ili više skupina koje se bira između alkila, -CN, -NRC(O)R,-C(O)OR, -C(O)NRaRb i halogena; monociklički nearomatski heterocikl, koji može biti supstituiran s jednom ili više skupina koje se bira između alkila, halogena, -CN i =O; ili alkil, koji može biti supstituiran s jednom ili više skupina koje se bira između halogena, hidroksi, alkoksi, -NRaRb, -NRC(O)R, -NRC(O)O(alkil), -NRC(O)N(R)2, -C(O)OR, tiol, alkiltiol, nitro, -CN, =O, -OC(O)H, -OC(O)(alkil), -OC(O)O(alkil), -OC(O)N(R)2 i -C(O)NRaRb; R3 je alkil, halogenalkil, hidroksialkil, alkoksialkil, cikloalkil, monociklički nearomatski heterocikl, monociklički heteroaromat ili fenil, gdje fenil, monociklički nearomatski heterocikl, te monociklička heteroaromatska skupina prikazana s R3 mogu biti supstituirani s jednom ili više skupina koji se biraju između alkila, halogena, halogenalkila, alkoksi, halogenalkoksi, nitro i -CN; R4 je halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -OC(O)O(alkil), -C(O)O(halogenalkil), -OC(O)R, -C(O)N(R)2, -OC(O)N(R)2, -NRC(O)R, -NRC(O)O(alkil), -S(O)R, -SO2R, -SO2N(R)2, -NRS(O)R, -NRSO2R, -NRC(O)N(R)2, -NRSO2N(R)2, halogenalkil, halogenalkoksi, cikloalkoksi, cikloalkil, monociklički nearomatski heterocikl, monociklički heteroaromatski ili alkil, gdje monociklički nearomatski heterocikl, monociklički heteroaromatski i alkilna skupina prikazana s R4 su koji može biti supstituiran s jednom ili više skupina koje se bira između -CN, -OR, -SR, -N(R)2, =O, -C(O)R, -C(O)OR, -C(O)O(halogenalkil), -OC(O)R, -OC(O)O(alkil), -C(O)N(R)2, -OC(O)N(R)2, -NRC(O)R, -NRC(O)O(alkil),-S(O)R, -SO2R, -SO2N(R)2, -NRS(O)R, -NRSO2R, -NRC(O)N(R)2 i -NRSO2N(R)2; svaki R je H ili alkil; Ra i Rb su neovisno H, alkil, ili se Ra i Rb može uzeti zajedno s dušikom na kojeg su vezani kako bi tvorili monociklički nearomatski heterocikl; i Rc je H, alkil ili halogen.
2. Spoj u skladu s patentnim zahtjevom 1, naznačen time što: R3 je alkil, halogenalkil, hidroksialkil, alkoksialkil, cikloalkil ili fenil, gdje fenil prikazan s R3 može biti supstituiran s jednom ili više skupina koji se biraju između alkila, halogena, halogenalkila, alkoksi, halogenalkoksi, nitro i -CN; R4 je halogen, -CN, -OR, -SR, -N(R)2, -C(O)R, -C(O)OR, -OC(O)O(alkil), -C(O)O(halogenalkil), -OC(O)R, -C(O)N(R)2, -OC(O)N(R)2, -NRC(O)R, -NRC(O)O(alkil), -S(O)R, -SO2R, -SO2N(R)2, -NRS(O)R, -NRSO2R, -NRC(O)N(R)2, -NRSO2N(R)2, halogenalkil, halogenalkoksi, cikloalkoksi, cikloalkil ili alkil, gdje alkilna skupina prikazana s R4 može biti supstituirana s jednom ili više skupina koje se bira između -CN, -OR, -SR, -N(R)2, =O, -C(O)R, -C(O)OR, -C(O)O(halogenalkil), -OC(O)R, -OC(O)O(alkil), -C(O)N(R)2, -OC(O)N(R)2, -NRC(O)R, -NRC(O)O(alkil),-S(O)R, -SO2R, -SO2N(R)2, -NRS(O)R, -NRSO2R, -NRC(O)N(R)2 i -NRSO2N(R)2.
3. Spoj u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je spoj prikazan sljedećom strukturnom formulom: [image] ; ili njegova farmaceutski prihvatljiva sol.
4. Spoj u skladu s patentnim zahtjevom 1 ili 2, naznačen time što je spoj prikazan sljedećom strukturnom formulom: [image] ; ili njegova farmaceutski prihvatljiva sol.
5. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što: R1 je metil ili -NH2; R2 je H ili metil, gdje metilna skupina prikazana s R2 može biti supstituirana s jednom ili više skupina koje se bira između halogena, hidroksi, alkoksi, -NRaRb, -NRC(O)R, -NRC(O)O(alkil),-NRC(O)N(R)2, -C(O)OR, tiola, alkiltiola, nitro, -CN, =O, -OC(O)H -OC(O)(alkil), -OC(O)O(alkil), -C(O)NRaRb i -OC(O)N(R)2; R3 je metil, etil, propil, izopropil, terc-butil, sec-butil, iso-butil, -CH2CF3, -CH(CH2F)2, -CH(CHF2)2, -CH(CF3)2, -CF(CH3)2, -CF3, ciklopropil, ciklobutil, ciklopentil cikloheksil, -C(OH)(CH3)2, -CH(OH)(CH3) ili fenil, gdje fenilna skupina prikazana s R3 može biti supstituirana s jednom ili više skupina koje se bira između alkila, halogena, halogenalkila, alkoksi, halogenalkoksi, nitro i -CN; i Rc, gdje je prisutan, je H.
6. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što: R1 je metil; R2 je -CH2OH; R3 je izopropil; i R4 je halogen, hidroksi, alkil, cikloalkil, cikloalkoksi, alkoksi, halogenalkoksi, halogenalkil, -N(R)2, -C(O)OH, -C(O)O(alkil), -C(O)O(halogenalkil), -C(O)(alkil), -C(O)N(R)2, -NRC(O)R, -SO2N(R)2, -OC(O)N(R)2, -CN, hidroksialkil ili dihidroksialkil.
7. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je R4 metil, etil, hidroksi, CF3, izopropil, ciklopropil, CH2OH, -CH(OH)(CH2)(OH), -C(OH)(CH3)2, -CH(OH)(CH3), -CH(OH)(CH2)(CH3), -CH(OH)(CH2)2(CH3), -C(O)NH2, C(O)N(CH3)2, -C(O)OH, -C(O)NH(CH3), C(O)CH3, C(O)CH2CH3, C(O)O(CH2)(CH3), -C(O)O (terc-butil), -C(O)O(C)(CH3)2(CF3), -NHC(O)CH3, -OCHF2, -OCF3, -OCH2CH3, -OCH(CH3)2 ili -OCH3.
8. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je R4 metil, CF3, ciklopropil, -OCHF2 ili -OCH3.
9. Spoj u skladu s bilo kojim od prethodnih patentnih zahtjeva, naznačen time što je R4 CF3.
10. Spoj u skladu s patentnim zahtjevom 1, naznačen time što je spoj prikazan strukturnom formulom koja se bira između: [image] ; [image] ; [image] ; [image] ; [image] ; i [image] ; ili farmaceutski prihvatljiva sol bilo kojeg od gore prikazanih.
11. Spoj u skladu s patentnim zahtjevom 10, naznačen time što je spoj prikazan sljedećom strukturnom formulom: [image] ; ili njegova farmaceutski prihvatljiva sol.
12. Farmaceutski pripravak, naznačen time što sadrži farmaceutsku podlogu ili razrjeđivač uz spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 11.
13. Spoj u skladu s bilo kojim od patentnih zahtjeva 1 do 11, naznačen time što je namijenjen upotrebi u liječenjeu subjekta s bolešću ili poremećajem koji se mogu liječiti pozitivnom regulacijom aktivnosti LXR.
14. Spoj, namijenjen upotrebi u skladu s patentnim zahtjevom 13, naznačen time što je bolest ili poremećaj hiperlipidemija, hiperkolesterolemija, hiperlipoproteinemija, hipertrigliceridemija, lipodistrofija, steatoza jetre, nealkoholni steatohepatitis (NASH), nealkoholna bolest masne jetre (NAFLD), hiperglicemija, otpornost na inzulin, dijabetes melitus, dislipidemija, ateroskleroza, bolest žučnih kamenaca, akne vulgaris, dermatitis, psorijaza, kontaktni dermatitis, atopični dermatitis, ekzem, povrede kože, starenje kože, fotostarenje, boranje, dijabetes, Niemann-Pickova bolest tip C, Parkinsonova bolest, Alzheimerova bolest, upala, ksantom, pretilost, metabolički sindrom, sindrom X, inzult, periferna okluzivna bolest, gubitak pamćenja, dijabetične neuropatije, proteinurija, glomerulopatije, dijabetična nefropatija, hipertenzivna nefropatija, IGA nefropatija, fokalna segmentalna glomeruloskleroza, hiperfosfatemija, kardiovaskularne komplikacije hiperfosfatemije, rak ili multipla skleroza.
15. Spoj, namijenjen upotrebi u skladu s patentnim zahtjevom 14, naznačen time što je bolest ili poremećaj ateroskleroza, Alzheimerova bolest, ekzem, psorijaza ili dermatitis, poput atopičnog dermatitisa ili kontaktnog dermatitisa.
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CA2866218A1 (en) 2013-09-19
US9814715B2 (en) 2017-11-14
US9006244B2 (en) 2015-04-14
CN104203951A (zh) 2014-12-10
US20150051214A1 (en) 2015-02-19
US9388190B2 (en) 2016-07-12
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US20150246924A1 (en) 2015-09-03
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CA2866218C (en) 2020-06-09
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