HRP20201304T1 - Spoj derivata 1,3,4-oksadiazol-amida koji služi kao inhibitor histonske deacetilaze 6 i farmaceutski pripravak koji sadrži taj spoj - Google Patents

Spoj derivata 1,3,4-oksadiazol-amida koji služi kao inhibitor histonske deacetilaze 6 i farmaceutski pripravak koji sadrži taj spoj Download PDF

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HRP20201304T1
HRP20201304T1 HRP20201304TT HRP20201304T HRP20201304T1 HR P20201304 T1 HRP20201304 T1 HR P20201304T1 HR P20201304T T HRP20201304T T HR P20201304TT HR P20201304 T HRP20201304 T HR P20201304T HR P20201304 T1 HRP20201304 T1 HR P20201304T1
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Jaekwang Lee
Moo Sung Ko
Younghue HAN
Yuntae Kim
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Chong Kun Dang Pharmaceutical Corp.
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Claims (9)

1. Spoj derivata 1,3,4-oksadiazol-amida, naznačen time, da je predstavljen sljedećom formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol: [image] u kojoj je svaki od L1 ili L3 neovisno veza ili –(C1-C2-alkilen)-; L2 je –(C1-C2-alkilen)-; svaki od Z1 do Z4 je neovisno N ili CRZ, gdje tri ili više od Z1 do Z4 ne mogu istovremeno biti N, i RZ je -H ili -X; R1 je –CX2H ili -CX3; R2 je –(C1-C4-alkil), –(C1-C4-alkil)-0 (C1-C4-alkil), –(C1-C4-alkil)-C(=O)-O (C1-C4-alkil), –(C3-C6-cikloalkil), -aril, -heteroaril, [image] dok najmanje jedan H od sljedećih: –(C3-C6-cikloalkil), -aril ili -heteroaril, može biti supstituiran sa sljedećima: -X, -OH, –(C1-C4-alkil), –O (C1-C4-alkil), –C(=O)-(C1-C4-alkil), –C(=O)-0 (C1-C4-alkil) ili -CF3, Y je -N-, -0- ili -S(=O)2-, kada Y je -N-, svaki od R4 i R8 neovisno je -H, –(C1-C4-alkil), –C(=O)-(C1-C4-alkil), –C(=O)-(C3-C6-cikloalkil), –C(=O)-0 (C1-C4-alkil), –C(=O)-CF3, –S(=O)2-(C1-C4-alkil), –(C2-C6-heterocikloalkil), benzil ili zaštitna amino-skupina, pri čemu –(C2-C6-heterocikloalkil) može sadržavati atom N, O ili S u prstenu, i kada Y je -O- ili S(=O)2-, R4 i R8 su nula, svaki od R5 do R8 neovisno je -H, –(C1-C4-alkil), -OH, -CH2OH ili -C(=O)-NH2, i svaki a do c je neovisno cijeli broj između 1, 2 ili 3; R3 je -(C1-C4-alkil), -(C1-C4-alkil)-0 (C1-C4-alkil), -(C1-C4-alkil)–C(=O)-0 (C1-C4-alkil), -(C3-C6-cikloalkil), -aril, -heteroaril, [image] ili [image] gdje najmanje jedan H od sljedećih: –(C3-C6-cikloalkil), -aril, ili -heteroaril, može biti svaki neovisno supstituiran sa sljedećima: -X, -OH, –(C1-C4-alkil), –O(C1-C4-alkil), –C(=O)-(C1-C4-alkil), –C(=O)-0 (C1-C4-alkil) ili -CF3, i R4, R5, R6, Y, a, b, R1, L1, Z1, Z2, Z3, i Z4 su isti kao što su prethodno definirani; i X je F, Cl, Br ili I.
2. Spoj derivata 1,3,4-oksadiazol-amida koji je predstavljen formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 1, naznačen time, da: L1 i L3 su veza; L2 je –(C1-C2-alkilen)-; svaki od Z1 do Z4 je neovisno N ili CRZ, gdje dva ili više od Z1 do Z4 ne mogu istovremeno biti N; i RZ je -H ili -X; R1 je –CX2H ili -CX3; R2 je –(C1-C4-alkil), –(C3-C6-cikloalkil), -aril, -heteroaril, [image] dok najmanje jedan H od sljedećih: –(C3-C6-cikloalkil), -aril, ili -heteroaril, može biti supstituiran sa sljedećima: -X, -OH, –(C1-C4-alkil), –O (C1-C4-alkil), –C(=O)-(C1-C4-alkil), –C(=O)-0 (C1-C4-alkil) ili -CF3, Y je -N-, -0- ili -S(=O)2-, kada Y je -N-, svaki od R4 i R8 neovisno je -H, –(C1-C4-alkil), –C(=0)-(C1-C4-alkil), -C(=0)-CF3, –S(=O)2-(C1-C4-alkil), –(C2-C6-heterocikloalkil), -C(=O)–(C3-C6-cikloalkil), benzil ili zaštitna amino-skupina, pri čemu –(C2-C6-heterocikloalkil) može sadržavati atom O u prstenu, i kada Y je -0- ili S(=O)2-, R4 i R8 su nula, svaki od R5 do R8 neovisno je -H, –(C1-C4-alkil), -OH, -CH2OH ili -C(=O)-NH2, i svaki a do c je neovisno cijeli broj između 1, 2 ili 3; R3 je -aril ili -heteroaril, pri čemu najmanje jedan H od -arila ili -heteroarila, može biti neovisno supstituiran sa sljedećima: -X, -OH, -(C1-C4-alkil), -O(C1-C4-alkil), –C(=O)-(C1-C4-alkil), –C(=O)-O(C1-C4-alkil) ili -CF3; i X je F, Cl, Br ili I.
3. Spoj derivata 1,3,4-oksadiazol-amida koji je predstavljen formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 2, naznačen time, da: L1 i L3 su veza; L2 je –(C1-alkilen)-; svaki od Z1 do Z4 je neovisno N ili CRZ, gdje dva ili više od Z1 do Z4 ne mogu istovremeno biti N, i RZ je -H ili -X; R1 je –CF2H ili -CF3; R2 je –(C1-C4-alkil), -piridinil ili [image] dok najmanje jedan H od piridinila može biti supstituiran sa sljedećima: -X, -OH, –(C1-C4-alkil), –0 (C1-C4-alkil), –C(=O)-(C1-C4-alkil), –C(=O)-0 (C1-C4-alkil) ili -CF3, Y je -N-, R4 je –(C1-C4-alkil), –C(=0)-(C1-C4-alkil) ili –S(=O)2-(C1-C4-alkil), svaki od R5 ili R6 neovisno je -H ili –(C1-C4-alkil), i svaki a i b je neovisno cijeli broj između 1 ili 2; R3 je -aril, pri čemu najmanje jedan H od -arila može biti supstituiran s -X; i X je F, Cl, Br ili I.
4. Spoj derivata 1,3,4-oksadiazol-amida koji je predstavljen formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 3, naznačen time, da: L1 i L3 su veza; L2 je –(C1-alkilen)-; svaki od Z1 do Z4 je neovisno N ili CRZ, gdje dva ili više od Z1 do Z4 ne mogu istovremeno biti N, i RZ je -H ili -X; R1 je –CF2H ili -CF3; R2 je piridinil ili [image] dok najmanje jedan H od piridinila može biti supstituiran sa sljedećima: -X, -OH, –(C1-C4-alkil), –0 (C1-C4-alkil), –C(=O)-(C1-C4-alkil), –C(=O)-0 (C1-C4-alkil) ili -CF3, Y je -N-, R4 je –(C1-C4-alkil), –C(=0)-(C1-C4-alkil) ili –S(=O)2-(C1-C4-alkil), svaki od R5 ili R6 neovisno je -H, i svaki a i b je neovisno cijeli broj između 1 ili 2; R3 je -aril, pri čemu najmanje jedan H od -arila može biti supstituiran s -X; i X je F, Cl, Br ili I.
5. Spoj derivata 1,3,4-oksadiazol-amida koji je predstavljen formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 1, naznačen time, da je spoj koji je predstavljen formulom I, odabran iz skupine koja se sastoji od spojeva opisanih u sljedećoj tablici: [image] (nastavak) [image] (nastavak) [image] (nastavak) [image] (nastavak) [image] (nastavak) [image] (nastavak) [image] (nastavak) [image]
6. Spoj derivata 1,3,4-oksadiazol-amida koji je predstavljen formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 5, naznačen time, da je spoj koji je predstavljen formulom I, odabran iz skupine koja se sastoji od spojeva opisanih u sljedećoj tablici: [image] (nastavak) [image]
7. Spoj derivata 1,3,4-oksadiazol-amida koji je predstavljen formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol, u skladu s patentnim zahtjevom 6, naznačen time, da je spoj koji je predstavljen formulom I, odabran iz skupine koja se sastoji od spojeva opisanih u sljedećoj tablici: [image]
8. Farmaceutski pripravak za uporabu u prevenciji ili liječenju bolesti posredovane histonskom deacetilazom, naznačen time, da on kao djelatni sastojak, sadrži spoj koji je predstavljen formulom I, njegov stereoizomer ili njegovu farmaceutski prihvatljivu sol, u skladu s bilo kojim od patentnih zahtjeva 1 do 7, pri čemu je bolest koja je posredovana histonskom deacetilazom, odabrana između infektivnih bolesti; neoplazmi; endokrinih, nutritivnih i metaboličkih bolesti; mentalnih poremećaja i poremećaja ponašanja; neuroloških bolesti; bolesti oka i adneksa; kardiovaskularnih bolesti; respiratornih bolesti; digestivnih bolesti; bolesti kože i potkožnog tkiva; bolesti mišićno-koštanog sustava i vezivnog sustava; ili kongenitalnih malformacija, deformacija i kromosomskih abnormalnosti.
9. Spoj koji je predstavljen formulom I, njegov stereoizomer ili njegova farmaceutski prihvatljiva sol, u skladu s bilo kojim od patentnih zahtjeva 1 do 7, naznačen time, da se upotrebljava u liječenju bolesti posredovane histonskom deacetilazom, pri čemu je bolest koja je posredovana histonskom deacetilazom, odabrana između infektivnih bolesti; neoplazmi; endokrinih, nutritivnih i metaboličkih bolesti; mentalnih poremećaja i poremećaja ponašanja; neuroloških bolesti; bolesti oka i adneksa; kardiovaskularnih bolesti; respiratornih bolesti; digestivnih bolesti; bolesti kože i potkožnog tkiva; bolesti mišićno-koštanog sustava i vezivnog sustava; ili kongenitalnih malformacija, deformacija i kromosomskih abnormalnosti.
HRP20201304TT 2015-07-27 2020-08-20 Spoj derivata 1,3,4-oksadiazol-amida koji služi kao inhibitor histonske deacetilaze 6 i farmaceutski pripravak koji sadrži taj spoj HRP20201304T1 (hr)

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KR20150106007 2015-07-27
PCT/KR2016/008216 WO2017018804A1 (ko) 2015-07-27 2016-07-27 히스톤 탈아세틸화효소 6 억제제로서의 1,3,4-옥사다이아졸 아마이드 유도체 화합물 및 이를 포함하는 약제학적 조성물
EP16830837.7A EP3330259B1 (en) 2015-07-27 2016-07-27 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same

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US11325286B2 (en) * 2009-09-24 2022-05-10 Sealed Air Corporation (Us) Mixing machine for producing foam within a bag
NZ739211A (en) 2015-07-27 2019-05-31 Chong Kun Dang Pharmaceutical Corp 1,3,4-oxadiazole amide derivative compound as histone deacetylase 6 inhibitor, and pharmaceutical composition containing same
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