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HRP20180844T1 - Terapeutski aktvni spojevi i postupci njihovog korištenja - Google Patents

Terapeutski aktvni spojevi i postupci njihovog korištenja Download PDF

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HRP20180844T1
HRP20180844T1 HRP20180844TT HRP20180844T HRP20180844T1 HR P20180844 T1 HRP20180844 T1 HR P20180844T1 HR P20180844T T HRP20180844T T HR P20180844TT HR P20180844 T HRP20180844 T HR P20180844T HR P20180844 T1 HRP20180844 T1 HR P20180844T1
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alkylene
alkyl
optionally substituted
ring
halo
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Giovanni Cianchetta
Byron Delabarre
Janeta Popovici-Muller
Francesco G. Salituro
Jeffrey O. Saunders
Jeremy Travins
Shunqi Yan
Tao Guo
Li Zhang
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Agios Pharmaceuticals, Inc.
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Publication of HRP20180844T1 publication Critical patent/HRP20180844T1/hr

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Claims (17)

1. Spoj koji ima Formulu I ili njegova farmaceutski prihvatljiva sol ili hidrat:  naznačen time da: prsten A proizvoljno je supstituiran monociklički heteroaril odabran iz niza koji čine oksazolil, izoksazolil, piridinil, pirimidinil, pirazinil i tiazolil, pri čemu je prsten A proizvoljno supstituiran s najviše dva supstituenta koji su neovisno odabrani iz niza koji čine halo, -C1-C4 alkil, -C1-C4 haloalkil, -C1-C4 hidroksialkil, -NH-S(O)2-(C1-C4 alkil), -S(O)2NH(C1-C4 alkil), -CN, -S(O)2-(C1-C4 alkil), C1-C4 alkoksi, -NH(C1-C4 alkil), -OH, -OCF3, -CN, -NH2, -C(O)NH2, -C(O)NH(C1-C4alkil), -C(O)-N(C1-C4Alkil)2, i ciklopropil proizvoljno supstituiran s OH; prsten B proizvoljno je supstituiran 6-člani monociklički aril ili monociklički heteroaril; R1 i R3 su svaki neovisno odabrani od vodika, C1-C4alkila, C1-C4 haloalkila, -O-C1-C4 alkila, i CN, pri čemu je bilo koji alkilni dio R1  proizvoljno supstituiran s -OH, NH2, NH(C1-C4alkil), ili N(C1-C4 alkil)2; R2 je odabran od: -(C1-C6 alkil), -(C2-C6 alkenil ili alkinil), -(C1-C6 alkilen)-N(R6)-(C1-C6 alkilen)-O-(C1-C6 alkil), -(C1-C6alkilen)-N(R6)-(C0-C6 alkilen)-Q, -(C1-C6 alkilen)-N(R6)(R6), -(C1-C6 alkilen)-N(R6)-S(O)1-2-(C1-C6 alkil), -(C1-C6 alkilen)-N(R6)-S(O)1-2-(C0-C6 alkil)-Q, -(C1-C6 alkilen)-S(O)1-2-N(R6)(R6), -(C1-C4 alkilen)-S(O)1-2-N(R6)-(C1-C6 alkilen)-Q, -C(O)N(R6)-(C1-C6 alkilen)-C(O)-(C0-C6 alkilen)-O-(C1-C6alkil), -C(O)N(R6)-(C1-C6 alkilen)-C(O)-(C0-C6 alkilen)-O-(C0-C6 alkilen)-Q, -(C1-C6 alkilen)-O-C(O)-(C1-C6 alkil), -(C1-C6alkilen)-O-C(O)-(C0-C6 alkil)-Q, -(C1-C6 alkilen)-O-(C1-C6alkil), -(C1-C6 alkilen)-O-(C1-C6 alkilen)-Q, -(C0-C6 alkilen)-C(O)-(C0-C6 alkilen)-O-(C1-C6 alkil), -(C0-C6 alkilen)-C(O)-(C0-C6 alkilen)-O-(C1-C6 alkilen)-Q, -(C1-C6 alkilen)-O-C(O)-(C1-C6 alkil), -(C1-C6 alkilen)-O-C(O)-(C0-C6 alkilen)-Q, -(C0-C6 alkilen)-C(O)N(R6)-(C1-C6 alkil), -(C0-C6 alkilen)-C(O)N(R6)-(C0-C6 alkilen)-Q, -(C1-C6 alkilen)-N(R6)C(O)-(C1-C6 alkil), -(C1-C6 alkilen)-N(R6)C(O)-(C0-C6 alkilen)-Q, -(C0-C6 alkilen)-S(O)0-2-(C1-C6 alkil), -(C0-C6 alkilen)-S(O)0-2-(C0-C6 alkilen)-Q, -(C1-C6 alkilen)-N(R6)-C(O)-N(R6)-(C1-C6 alkil), -(C0-C6 alkilen)-Q, -(C0-C6 alkilen)-C(O)-(C1-C6 alkil), -(C0-C6 alkilen)-C(O)-(C0-C6 alkilen)-Q, pri čemu: bilo koja skupina alkila ili alkilena koja je prisutna u R2 je proizvoljno supstituirana s jednim ili više -OH, -O(C1-C4 alkil) ili halo; bilo koji terminalni metilni dio koji je prisutan u R2 je proizvoljno zamijenjen s -CH2OH, CF3, -CH2F, -CH2Cl, C(O)CH3, C(O)CF3, CN, ili CO2H; svaki R6  neovisno je odabran od vodika i C1-C6 alkila; i Q je odabran od arila, heteroarila, karbociklila i heterociklila, bilo koji od njih je proizvoljno supstituiran; ili su R1 i R3 proizvoljno uzeti zajedno s ugljikovim atomom na koji su vezani da tvore C(=O), ili R1 i R2 su proizvoljno uzeti zajedno da tvore supstituiran karbociklil ili proizvoljno supstituiran heterociklil; a. kada je prsten A proizvoljno supstituiran piridil i prsten B je proizvoljno supstituiran fenil; zatim dio spoja koji predstavlja -NH-C(R1)(R2)(R3) nije -NH(CH2)-aril; b. kada je prsten A piridin-3-il proizvoljno supstituiran s jednim ili više supstituenata odabranih od halo, metil ili CF3, i prsten B je fenil proizvoljno supstituiran s jednim ili više supstituenata odabranih od halo, metil, CF3; metoksi, ili CH=C(fenil)CN; zatim dio spoja koji predstavlja -NH-C(R1)(R2)(R3) je različit od -NH(C1-C8 alkilen)-N(Ra)(Ra), -NH-1-(aminometil)ciklopentilmetil, -NH-4-(aminometil)cikloheksilmetil, pri čemu svaki Ra je vodik, C1-C4 alkil ili dva Ra su uzeti zajedno s dušikom za koji su obično vezani tako da tvore morfolin-4-il ili pipieridin-1-il; c. spoj nije: 4-((4-((furan-2-ilmetil)amino)-6-(piridin-4-il)-1,3,5-triazin-2-il)amino)fenol, i 2-kloro-4-(metilsulfonil)-N-[4-(fenilamino)-6-(2-piridinil)-1,3,5-triazin-2-il]-benzamid.
2. Spoj prema zahtjevu 1, naznačen time da je R1  neovisno odabran od vodika, -CH3, -CH2CH3, -CH2OH, CN, ili R1 i R3 su uzeti zajedno da tvore =O, ili pri čemu su R1 i R2  uzeti zajedno da tvore karbociklil ili heterociklil, bilo koji od njih je proizvoljno supstituiran s do 3 supstituenta koji su neovisno odabrani od halo, C1-C4 alkil, C1-C4 haloalkil, C1-C4 alkoksija, -CN, =O, -OH, i -C(O)C1-C4 alkila.
3. Spoj prema zahtjevu 1, naznačen time da je R2 odabran od: -(C1-C4 alkil) proizvoljno supstituiran s fluoro ili -OH; -(C0-C4 alkilen)-O-(C1-C4alkil), -(C0-C2 alkilen)-N(R6)-(C1-C6 alkil), -(C0-C2 alkilen)-Q, te -O-(C0-C2 alkilen)-Q, pri čemu je Q proizvoljno supstituiran s do 3 supstituenta koji su neovisno odabrani od C1-C4 alkila, C1-C4 haloalkila, C1-C4 alkoksija, =O, -C(O)-C1-C4 alkila, -CN, i halo.
4. Spoj prema zahtjevu 3, naznačen time da je Q odabran od tetrahidrofuranila, ciklobutila, ciklopropila, fenila, pirazolila, morfolinila i oksetanila, pri čemu je Q proizvoljno supstituiran s do 2 supstituenta koji su neovisno odabrani od C1-C4 alkila, C1-C4 haloalkila, =O, fluora, klora te broma.
5. Spoj prema zahtjevu 1, naznačen time da R1 i R2 su uzeti zajedno da tvore ciklopropil, ciklobutil, ciklopentil, cikloheksil, tetrahidrofuranil, oksetanil, biciklo[2.2.1]heptanil, azetidinil, fenil bilo koji od njih je proizvoljno supstituiran s do 2 supstituenta koji su neovisno odabrani od C1-C4 alkila, C1-C4 alkoksija, C3-C6 cikloalkila, -OH, -C(O)CH3, fluora, i klora, ili pri čemu je prsten A proizvoljno supstituiran s do dva supstituenta koji su neovisno odabrani od halo, -C1-C4 alkila, -C1-C4 haloalkila, -C1-C4 hidroksialkila, -NH-S(O)2-(C1-C4 alkil), -S(O)2NH(C1-C4 alkil), -CN, -S(O)2-(C1-C4alkil), C1-C4 alkoksija, -NH(C1-C4 alkil), -OH, i -NH2, ili pri čemu je prsten B odabran od fenila, piridinila, pirimidinila, piridazinila, i pirazinila, pri čemu je prsten B proizvoljno supstituiran s do dva supstituenta koji su neovisno odabrani od halo, -C1-C4 alkila, -C2-C4alkinila, -C1-C4 haloalkila, -C1-C4 hidroksialkila, C3-C6 cikloalkila, -(C0-C2 alkilen)-O-C1-C4alkil, -O-(C1-C4 alkilen)-C3-C6 cikloalkila, -NH-S(O)2-(C1-C4alkil), -S(O)2NH(C1-C4 alkil), - S(O)2-NH-(C3-C6 cikloalkil), -S(O)2-(zasićeni heterociklil),-CN, -S(O)2-(C1-C4 alkil), -NH(C1-C4 alkil), -N(C1-C4 alkil)2, -OH, C(O)-O-(C1-C4 alkil), zasićenog heterociklila i -NH2.
6. Spoj prema zahtjevu 1 koji ima strukturnu formulu II:  ili njegova farmaceutski prihvatljiva sol, naznačen time da: prsten A' je piridin-2-il, pri čemu je proizvoljno supstituiran s jednim ili dva supstituenta koji su neovisno odabrani od klora, fluora, -CF3, -CHF2, -CH3, -CH2CH3, -CF2CH3, -OH, -OCH3, -OCH2CH3, -NH2, -NH(CH3), i -N(CH3)2; prsten B' je odabran od piridin-3-ila, piridin-4-ila, i pirimidin-5-ila, pri čemu je prsten B' proizvoljno supstituiran s jednim do dva supstituenata koji su neovisno odabrani od halo; -CN; -OH; C1-C4alkila proizvoljno supstituiranog s halo, CN ili -OH; -S(O)2-C1-C4 alkila; -S(O)-C1-C4 alkila; -S(O)2-NH-C1-C4 alkila; -S(O)2-N(C1-C4 alkil)2; -S(O)2-azetidin-1-ila; -O-C1-C4 alkila; -CH2-O-CH3, morfolin-4-ila, ciklopropila, -S(O)2-NH-ciklopropila; -C(O)-O-CH3; i -C(R1a)(R2a)(R3a) je odabran od C1-C6 alkila proizvoljno supstituiranog s halo ili -OH; -(C0-C1 alkilen)-cikloalkilom, pri čemu je alkilen proizvoljno supstituiran metilom i cikloalkil je proizvoljno supstituiran s halo, -OCH3 ili metilom; zasićeni heterociklil je proizvoljno supstituiran s halo ili metilom; -C(O)-O-C1-C6 alkil; -C(O)-(C0-C1 alkilen)-ciklopropil; i C(O)-benzil.
7. Spoj prema zahtjevu 6, naznačen time da je prsten A' odabran od 6-aminopiridin-2-ila, 6-kloropiridin-2-ila i 6-trifluorometilpiridin-2-ila.
8. Spoj prema zahtjevu 6, naznačen time da je prsten B' odabran iz niza koji sadrži 2-(morfolin-4-il)piridin-4-il, 2-dimetilaminopiridin-4-il, 3-(2-metoksietil)fenil, 3,5-difluorofenil, 3-klorofenil, 3-cijanometilfenil, 3-cijanofenil, 3-ciklopropilaminosulfonilfenil, 3-dimetilaminosulfonilfenil, 3-etilsulfonilfenil, 3-fluorofenil, 3-metilsulfonilfenil, 4-fluorofenil, 5-kloropiridin-3-il, 5-cijanopiridin-3-il, 5-cijanopiridin-3-il, 5-cijanopiridin-4-il, 5-fluoropiridin-3-il, 5-trifluorometilpiridin-3-il, 6-kloropiridin-4-il, 6-cijanopiridin-4-il, 6-ciklopropilpiridin-4-il, 6-etoksipiridin-4-il, 6-fluoropiridin-3-il, 6-fluoropiridin-4-il, 6-metilpiridin-4-il, 6-trifluorometilpiridin-4-il, fenil i piridin-4-il, i pri čemu je skupina predstavljena s C(R1a)(R2a)(R3a) odabrana iz niza koji čine 2-hidroksiciklopentil, 2-metilciklopropil, 3,3-difluorociklobutil, -(CH2)3CH3, -CH(CH3)-C(CH3)3, -CH(CH3)-CH2OCH3, -C(O)-C(CH3)3, -C(O)-CH(CH3)2, -C(O)-ciklopropil, -C(O)-OC(CH3)3, -C(O)-OCH2CH(CH3)2, -C(O)-OCH2CH3, -CH(CH3)-CH(CH3)2, -CH(CH3)-CH2CH3, -CH2C(CH3)2-CH2OH, CH2C(CH3)3, -CH2CF3, -CH2CH(CH3)2, -CH2CH(CH3)-CH2CH3, -CH2CH2CH(CH3)2, -CH2-ciklopropil, ciklobutil, cikloheksil, ciklopentil, ciklopropil, izopropil, oksetan-3-il, biciklo[2.2.1]heptanil, tertrahidropiran-4-il, i tetrahidropiran-3-il.
9. Farmaceutski pripravak naznačen time da sadrži spoj prema zahtjevu 1 te farmaceutski prihvatljiv nosač.
10. Farmaceutski pripravak prema zahtjevu 9, naznačen time da nadalje sadrži drugo terapeutsko sredstvo koje je korisno u liječenju raka.
11. Spoj prema bilo kojem od zahtjeva 1 do 10 ili farmaceutski pripravak prema zahtjevima 9 ili 10, za uporabu za liječenje raka naznačen time da ima prisutnost mutacije izocitrat dehidrogenaze 2 (IDH2), pri čemu mutacija IDH2 rezultira novom sposobnošću enzima da katalizira NADPH-ovisnu redukciju α-ketoglutarata u R(-)-2-hidroksiglutarat kod pacijenta.
12. Spoj ili farmaceutski pripravak za uporabu prema zahtjevu 11, naznačen time da IDH2 mutacija je mutacija IDH2 R140Q ili R172K; ili pri čemu je mutacija IDH2 mutacija IDH2 R140Q.
13. Spoj ili farmaceutski pripravak za uporabu prema zahtjevu 11, naznačen time da je rak odabran od glioblastoma (ili glioma), mijelodisplastičnog sindroma (MDS), mijeloproliferativnih novotvorina (MPN), akutne mijelogene leukemije (AML), sarkoma, melanoma, karcinoma pluća nemalih stanica, hondrosarkoma, kolangiokarcinoma i angioimunoblastičnog ne-Hodgkinovog limfoma (NHL).
14. Spoj ili farmaceutski pripravak za uporabu prema zahtjevu 11, naznačen time da nadalje sadrži drugo terapeutsko sredstvo koje je korisno u liječenju raka.
15. Spoj prema zahtjevu 1, naznačen time da je 
16. Spoj prema zahtjevu 1, naznačen time da je 
17. Spoj prema zahtjevu 1, naznačen time da je 
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Families Citing this family (99)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102985557B (zh) 2009-03-13 2018-06-15 安吉奥斯医药品有限公司 用于细胞增殖相关病症的方法和组合物
EP3241554B1 (en) 2009-06-29 2020-01-29 Agios Pharmaceuticals, Inc. Quinoline-8-sulfonamide derivatives having an anticancer activity
CA2793836C (en) 2009-10-21 2020-03-24 Agios Pharmaceuticals, Inc. Methods and compositions for cell-proliferation-related disorders
WO2011050210A1 (en) 2009-10-21 2011-04-28 Agios Pharmaceuticals, Inc. Methods and compositions for cell-proliferation-related disorders
CN108451955B (zh) 2011-05-03 2022-02-01 安吉奥斯医药品有限公司 用于治疗的丙酮酸激酶活化剂
CN102827170A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN102827073A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
AU2013207252B2 (en) 2012-01-06 2016-06-09 H.Lundbeck A/S Carbamate compounds and pharmaceutical compositions thereof
CN115521264A (zh) 2012-01-06 2022-12-27 法国施维雅药厂 治疗活性化合物及其使用方法
US9474779B2 (en) 2012-01-19 2016-10-25 Agios Pharmaceuticals, Inc. Therapeutically active compositions and their methods of use
US10202339B2 (en) 2012-10-15 2019-02-12 Agios Pharmaceuticals, Inc. Therapeutic compounds and compositions
MY185687A (en) * 2013-07-11 2021-05-30 Agios Pharmaceuticals Inc N,6-bis(aryl or heteroaryl)-1,3,5-triazine-2,4-diamine compounds as idh2 mutants inhibitors for the treatment of cancer
WO2015003360A2 (en) * 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
US9579324B2 (en) 2013-07-11 2017-02-28 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
JP6529492B2 (ja) * 2013-07-11 2019-06-12 アジオス ファーマシューティカルズ， インコーポレイテッド 癌の処置のためのｉｄｈ２突然変異体阻害剤としての２，４−または４，６−ジアミノピリミジン化合物
WO2015003355A2 (en) * 2013-07-11 2015-01-15 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
CN105473560B (zh) * 2013-07-11 2020-01-17 安吉奥斯医药品有限公司 治疗活性化合物及其使用方法
US20150031627A1 (en) 2013-07-25 2015-01-29 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
UA121021C2 (uk) * 2013-08-02 2020-03-25 Аджіос Фармасьютікалз, Інк. Терапевтично активні сполуки і способи їх застосування
KR102316886B1 (ko) * 2013-08-02 2021-10-19 아지오스 파마슈티컬스 아이엔씨. 치료학적 활성 화합물 및 이의 사용방법
WO2015018060A1 (en) * 2013-08-09 2015-02-12 Agios Pharmaceuticals, Inc. Crystalline forms of therapeutically active compounds and use thereof
TWI651310B (zh) * 2014-02-20 2019-02-21 日商日本煙草產業股份有限公司 三化合物及其醫藥用途
KR20240010105A (ko) * 2014-03-14 2024-01-23 아지오스 파마슈티컬스 아이엔씨. 치료적으로 활성인 화합물의 약제학적 조성물
MA39725B1 (fr) * 2014-03-14 2021-09-30 Les Laboratoires Servier Sas Compositions pharmaceutiques de composés thérapeutiquement actifs
CN106132946A (zh) * 2014-03-28 2016-11-16 巴斯夫欧洲公司 作为除草剂的二氨基三嗪衍生物
WO2015155129A1 (en) * 2014-04-07 2015-10-15 Basf Se Diaminotriazine compound
EP2930174A1 (en) * 2014-04-07 2015-10-14 Basf Se Diaminotriazine derivatives as herbicides
MX372964B (es) 2014-09-19 2020-03-27 Forma Therapeutics Inc Derivados de fenil quinolinona como inhibidores de isocitrato deshidrogenasa mutante (mt-idh)
AU2015317327B9 (en) * 2014-09-19 2020-04-09 Forma Therapeutics, Inc. Pyridinyl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors
CN111909130B (zh) * 2014-09-19 2023-10-31 福马治疗股份有限公司 作为突变型异柠檬酸脱氢酶抑制剂的吡啶-2(1h)-酮喹啉酮衍生物
US9815817B2 (en) 2014-09-19 2017-11-14 Forma Therapeutics, Inc. Quinolinone pyrimidines compositions as mutant-isocitrate dehydrogenase inhibitors
JP2017529382A (ja) * 2014-09-29 2017-10-05 アギオス ファーマシューティカルス，インコーポレーテッド 治療活性を有する化合物及びその使用方法
US10201543B2 (en) 2015-02-04 2019-02-12 Agios Pharmaceuticals, Inc. Therapeutically active compounds and their methods of use
WO2016149401A2 (en) 2015-03-18 2016-09-22 Abide Therapeutics, Inc. Piperazine carbamates and methods of making and using same
WO2016171755A1 (en) 2015-04-21 2016-10-27 Forma Therapeutics, Inc. Fused-bicyclic aryl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors
EA038574B1 (ru) * 2015-04-21 2021-09-16 Форма Терапьютикс, Инк. Хинолиноновые производные пиридин-2(1h)-она и фармацевтические композиции на их основе
WO2016171756A1 (en) * 2015-04-21 2016-10-27 Forma Therapeutics, Inc. Quinolinone five-membered heterocyclic compounds as mutant-isocitrate dehydrogenase inhibitors
US20180134683A1 (en) * 2015-05-07 2018-05-17 Teligene Ltd. Heterocylcic compounds as idh2 inhibitors
AU2016262459A1 (en) 2015-05-11 2017-12-21 H. Lundbeck A/S. Methods of treating inflammation or neuropathic pain
HRP20231247T1 (hr) 2015-06-11 2024-02-02 Agios Pharmaceuticals, Inc. Postupci uporabe aktivatora piruvat kinaze
AU2016299092B2 (en) * 2015-07-30 2020-08-20 Centaurus Biopharma Co., Ltd. 1, 3, 5-triazine derivative and method of using same
EP3331866B1 (en) * 2015-08-05 2023-07-26 Les Laboratoires Servier Methods of preparing a 6-heteroaryl-1,3,5-triazine-2,4-diol and a 6-heteroaryl-1,3,5-triazine-2,4-diamine
US10905692B2 (en) 2015-10-15 2021-02-02 Agios Pharmaceuticals, Inc. Combination therapy for treating malignancies
JP7033061B2 (ja) 2015-10-15 2022-03-09 アジオス ファーマシューティカルズ， インコーポレイテッド 悪性腫瘍を処置するため組合せ療法
EP3362070B1 (en) 2015-10-15 2021-01-27 Celgene Corporation Combination of a mutant isocitrate dehydrogenase 2 inhibitor with azacitidine and its use for treating acute myelogenous leukemia
FI3362065T3 (fi) 2015-10-15 2024-06-19 Servier Lab Ivosidenibiä, sytarabiinia ja daunorubisiinia tai idarubisiinia käsittävä yhdistelmähoito akuutin myelooisen leukemian hoitamiseksi
AU2016340740B2 (en) * 2015-10-21 2018-07-19 NeuForm Pharmaceuticals, Inc. Deuterated compounds for treating hematologic malignancies, and compositions and methods thereof
JP6852073B2 (ja) * 2015-12-04 2021-03-31 アジオス ファーマシューティカルズ， インコーポレイテッド 悪性病変を処置する方法
CN105384702B (zh) * 2015-12-11 2018-04-10 浙江大学 三取代均三嗪类化合物及其制备方法
CN105503754B (zh) * 2015-12-11 2017-11-17 浙江大学 2‑氨基‑4‑苄基‑6‑吗啉‑1,3,5‑三嗪及其制备和应用
CN105399695B (zh) * 2015-12-11 2019-04-19 浙江大学 三嗪类化合物及其制备方法和用途
WO2017143283A1 (en) 2016-02-19 2017-08-24 Abide Therapeutics, Inc. Radiolabeled monoacylglycerol lipase occupancy probe
WO2017140758A1 (en) 2016-02-19 2017-08-24 Debiopharm International S.A. Derivatives of 2-amino-4-(2-oxazolidinon-3-yl)-pyrimidine fused with a five-membered heteroaromatic ring in 5,6-position which are useful for the treatment of various cancers
AU2016393869B2 (en) 2016-02-26 2022-10-27 Celgene Corporation IDH2 inhibitors for the treatment of haematological maligancies and solid tumours
CN105820133B (zh) * 2016-03-25 2018-06-05 浙江工业大学 多取代均三嗪类化合物及其制备方法和应用
CN105753801B (zh) * 2016-03-25 2018-06-01 浙江工业大学 一种均三嗪类化合物的制备方法
EP3489230B1 (en) * 2016-07-21 2021-12-08 Nanjing Sanhome Pharmaceutical Co., Ltd. Chemical compound of isocitrate dehydrogenase inhibitor, and application thereof
WO2018026894A1 (en) 2016-08-03 2018-02-08 Celgene Corporation Methods of treatment of myelodysplastic syndrome
IL265126B2 (en) 2016-09-07 2023-12-01 Celgene Corp Composition of tablets of 2-METHYL-1-[(4-[6-(TRIFLUOROMETHYL)PYRIDIN-2-YL]-6-{[2-(TRIFLUOROMETHYL)PYRIDIN-4-YL]AMINO}-1,3,5- TRIAZIN–2–YL)AMINO]PROPAN–2–OL AND ITS SALTS
EP3515897B1 (en) 2016-09-19 2021-08-18 H. Lundbeck A/S Piperazine carbamates as modulators of magl and/or abhd6 and their use
JOP20190106A1 (ar) 2016-11-16 2019-05-09 Lundbeck La Jolla Research Center Inc مثبطات أحادي أسيل جليسرول ليباز (magl)
JOP20190105A1 (ar) 2016-11-16 2019-05-09 Lundbeck La Jolla Research Center Inc مثبطات أحادي أسيل جليسرول ليباز (magl)
ES2924500T3 (es) 2017-01-22 2022-10-07 Chia Tai Tianqing Pharmaceutical Group Co Ltd Sal de derivado de 1,3,5-triazina, cristal, método de preparación, composición farmacéutica y uso de la misma
US11229653B2 (en) 2017-05-05 2022-01-25 Celgene Corporation Methods of treatment of myeloproliferative neoplasm
WO2019006299A1 (en) 2017-06-30 2019-01-03 Celgene Corporation COMPOSITIONS AND METHODS FOR THE USE OF 2- (4-CHLOROPHENYL) -N - ((2- (2,6-DIOXOPIPERIDIN-3-YL) -1-OXOISOINDOLIN-5-YL) METHYL) -2,2-DIFLUOROACETAMIDE
CN109265444B (zh) * 2017-07-17 2022-03-11 南京圣和药业股份有限公司 取代的三嗪类idh抑制剂的光学异构体及其应用
CN109467538A (zh) 2017-09-07 2019-03-15 和记黄埔医药（上海）有限公司 环烯烃取代的杂芳环类化合物及其用途
CN110051673B (zh) * 2018-01-19 2022-03-11 南京圣和药业股份有限公司 一种包含三嗪类idh抑制剂的药物组合物及其用途
CN110054617A (zh) * 2018-01-19 2019-07-26 南京圣和药业股份有限公司 三嗪类化合物、其制备方法及用途
CN110054616B (zh) * 2018-01-19 2021-11-23 南京圣和药业股份有限公司 三嗪类idh抑制剂的制备方法
CN110054615B (zh) * 2018-01-19 2021-06-15 南京圣和药业股份有限公司 三嗪类idh抑制剂甲磺酸盐的晶型
JP2021523200A (ja) 2018-05-15 2021-09-02 ルンドベック ラ ホーヤ リサーチ センター，インク． Ｍａｇｌ阻害剤
US10532047B2 (en) 2018-05-16 2020-01-14 Forma Therapeutics, Inc. Solid forms of ((S)-5-((1-(6-chloro-2-oxo-1,2-dihydroquinolin-3-yl)ethyl)amino)-1-methyl-6-oxo-1,6-dihydropyridine-2-carbonitrile
US11311527B2 (en) 2018-05-16 2022-04-26 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mIDH-1)
EP3720442B1 (en) 2018-05-16 2022-12-28 Forma Therapeutics, Inc. Inhibiting mutant idh-1
US11013734B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Treating patients harboring an isocitrate dehydrogenase-1 (IDH-1) mutation
US11013733B2 (en) 2018-05-16 2021-05-25 Forma Therapeutics, Inc. Inhibiting mutant isocitrate dehydrogenase 1 (mlDH-1)
US10980788B2 (en) 2018-06-08 2021-04-20 Agios Pharmaceuticals, Inc. Therapy for treating malignancies
KR102328682B1 (ko) * 2018-08-27 2021-11-18 주식회사 대웅제약 신규한 헤테로사이클릭아민 유도체 및 이를 포함하는 약학 조성물
US20220017489A1 (en) 2018-11-02 2022-01-20 Celgene Corporation Solid dispersions for treatment of cancer
US12215094B2 (en) 2018-11-02 2025-02-04 Celgene Corporation Solid forms of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl) amino]propan-2-ol
US20220017490A1 (en) 2018-11-02 2022-01-20 Celgene Corporation Co-crystals of 2-methyl-1 -[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl) pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol, compositions and methods of use thereof
CN111662271B (zh) * 2019-03-08 2023-11-14 中国药科大学 具有idh突变体抑制活性的化合物及其制备方法与应用
CN111662275B (zh) * 2019-03-08 2023-08-22 中国药科大学 苯磺酰胺类idh突变体抑制剂、其制备方法和用途
WO2020239759A1 (en) 2019-05-27 2020-12-03 Sandoz Ag Amorphous enasidenib in a stabilized form
WO2021057975A1 (zh) * 2019-09-29 2021-04-01 贝达药业股份有限公司 突变型idh2抑制剂及其应用
KR20220101148A (ko) 2019-11-14 2022-07-19 셀진 코포레이션 암의 치료를 위한 소아용 제제
MX2022013224A (es) 2020-04-21 2022-11-14 H Lundbeck As Sintesis de un inhibidor de la monoacilglicerol lipasa.
CN111592524B (zh) * 2020-05-20 2023-11-17 温州市天聚万迅信息科技有限公司 恩西德尼的制备方法
WO2022074587A1 (en) * 2020-10-06 2022-04-14 Kures, Inc. Mu-opioid receptor agonists and uses therefor
KR20230145402A (ko) * 2021-02-12 2023-10-17 르 라보레또레 쎄르비에르 치료적 활성 화합물 및 이의 사용 방법
US11865079B2 (en) 2021-02-12 2024-01-09 Servier Pharmaceuticals Llc Therapeutically active compounds and their methods of use
CN113461660B (zh) * 2021-06-11 2022-08-02 浙江大学 2,4,6-三取代-1,3,5-均三嗪类化合物及制备和应用
US20250051301A1 (en) * 2022-03-15 2025-02-13 Betta Pharmaceuticals Co., Ltd Mutant idh1 and idh2 inhibitor and application thereof
WO2023183520A1 (en) * 2022-03-24 2023-09-28 A2A Pharmaceuticals, Inc. Compositions and methods for treating cancer
CN114773320A (zh) * 2022-05-29 2022-07-22 重庆医科大学 1,3,5-三嗪化合物及其制备方法和用途
CN115536637B (zh) * 2022-10-24 2025-03-18 陕西中医药大学 一种均三嗪类衍生物及其合成方法与用途
CN115819363B (zh) * 2022-12-16 2025-04-01 浙江工业大学 酮酰胺类化合物及其制备方法和应用
WO2025072722A1 (en) * 2023-09-27 2025-04-03 A2A Pharmaceuticals, Inc. Methods for treating cancers associated with transforming acidic coiled-coil proteins

Family Cites Families (93)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2390529A (en) 1942-02-03 1945-12-11 Ernst A H Friedheim Hydrazino-1,3,5-triazino derivatives of substituted phenylarsenic compounds
BE754242A (fr) 1970-07-15 1971-02-01 Geigy Ag J R Diamino-s-triazines et dinitro-s-triazines
US3867383A (en) 1971-03-29 1975-02-18 Ciba Geigy Corp Monoanthranilatoanilino-s-triazines
CH606334A5 (hr) 1974-06-21 1978-10-31 Ciba Geigy Ag
JPS58186682A (ja) 1982-04-27 1983-10-31 日本化薬株式会社 セルロ−ス又はセルロ−ス含有繊維材料の染色法
DE3512630A1 (de) 1985-04-06 1986-10-23 Hoechst Ag, 6230 Frankfurt Verfahren zum faerben oder bedrucken von cellulosefasern oder cellulosemischfasern
US5041443A (en) 1989-02-21 1991-08-20 Dainippon Pharmaceutical Co., Ltd. Medicament for treating cerebral insufficiency diseases, novel 2-(1-piperazinyl)-4-phenylcycloalkanopyrimidine derivatives, and process for the production thereof
ATE107922T1 (de) 1989-03-03 1994-07-15 Dainippon Pharmaceutical Co 2-(1-piperazinyl)-4-phenylcycloalkanpyridin- derivate, verfahren zu deren herstellung und pharmazeutische zusammensetzungen, die sie enthalten.
EP0466647B1 (de) * 1990-07-12 1995-11-29 Ciba-Geigy Ag Verfahren zur photochemischen und thermischen Stabilisierung von Polyamid-Fasermaterialien
JPH0499768A (ja) 1990-08-17 1992-03-31 Dainippon Pharmaceut Co Ltd ４―（４―フェニルピリジン―２―イル）ピペラジン―１―オキシド誘導体
DE69322076D1 (de) 1992-02-28 1998-12-17 Zenyaku Kogyo Kk S-triazin-derivate und diese als aktiven wirkstoff enthaltende heilmittel gegen östrogen abhängige krankheiten
IL115420A0 (en) 1994-09-26 1995-12-31 Zeneca Ltd Aminoheterocyclic derivatives
WO1998021191A1 (fr) 1995-05-16 1998-05-22 Nissan Chemical Industries, Ltd. Derives de cyanoethylmelamine et procede de production
FR2735127B1 (fr) 1995-06-09 1997-08-22 Pf Medicament Nouvelles piperazines heteroaromatiques utiles comme medicaments.
GB9602166D0 (en) 1996-02-02 1996-04-03 Zeneca Ltd Aminoheterocyclic derivatives
JPH09291034A (ja) 1996-02-27 1997-11-11 Yoshitomi Pharmaceut Ind Ltd 縮合ピリジン化合物およびその医薬としての用途
AU722662B2 (en) 1996-05-20 2000-08-10 Darwin Discovery Limited Quinoline sulfonamides as TNF inhibitors and as PDE-IV inhibitors
US5984882A (en) 1996-08-19 1999-11-16 Angiosonics Inc. Methods for prevention and treatment of cancer and other proliferative diseases with ultrasonic energy
US6399358B1 (en) 1997-03-31 2002-06-04 Thomas Jefferson University Human gene encoding human chondroitin 6-sulfotransferase
JPH11158073A (ja) * 1997-09-26 1999-06-15 Takeda Chem Ind Ltd アデノシンａ３拮抗剤
US7517880B2 (en) 1997-12-22 2009-04-14 Bayer Pharmaceuticals Corporation Inhibition of p38 kinase using symmetrical and unsymmetrical diphenyl ureas
UY25842A1 (es) 1998-12-16 2001-04-30 Smithkline Beecham Corp Antagonistas de receptores de il-8
AU5379900A (en) 1999-06-07 2000-12-28 Shire Biochem Inc. Thiophene integrin inhibitors
NZ517426A (en) 1999-08-27 2004-04-30 Sugen Inc Phosphate mimics and methods of treatment using phosphatase inhibitors
JP4688401B2 (ja) 2000-07-03 2011-05-25 関西ペイント株式会社 ガスバリヤー性フィルム
NZ523526A (en) 2000-07-20 2004-10-29 Neurogen Corp Diaryl piperazines as capsaicin receptor ligands
JP2005500294A (ja) 2001-06-19 2005-01-06 ブリストル−マイヤーズ　スクイブ　カンパニー ホスホジエステラーゼ７に対するピリミジン阻害剤
EP1423371B1 (en) 2001-08-17 2010-10-20 Basf Se Triazine derivatives and their use as sunscreens
JP4753336B2 (ja) 2001-09-04 2011-08-24 日本化薬株式会社 新規アリル化合物及びその製法
US7291616B2 (en) * 2001-10-31 2007-11-06 Cell Therapeutics, Inc. Aryl triazines as LPAAT-β inhibitors and uses thereof
US6878196B2 (en) 2002-01-15 2005-04-12 Fuji Photo Film Co., Ltd. Ink, ink jet recording method and azo compound
US20040067234A1 (en) 2002-07-11 2004-04-08 Paz Einat Isocitrate dehydrogenase and uses thereof
SI2256108T1 (sl) 2002-07-18 2016-05-31 Janssen Pharmaceutica N.V. Substituirani triazinski kinazni inhibitorji
JP2004107220A (ja) 2002-09-13 2004-04-08 Mitsubishi Pharma Corp ＴＮＦ−α産生抑制剤
AR042052A1 (es) 2002-11-15 2005-06-08 Vertex Pharma Diaminotriazoles utiles como inhibidores de proteinquinasas
AU2003293333A1 (en) 2002-12-02 2004-06-23 Arqule, Inc. Method of treating cancers
ES2373947T3 (es) 2002-12-16 2012-02-10 Genmab A/S Anticuerpos monoclonales humanos contra interleucina 8 (il-8).
BRPI0406667A (pt) 2003-01-10 2005-12-20 Threshold Pharmaceuticals Inc Método para o tratamento de câncer, e, formulação terapeuticamente aceitável de 2-dg
US7358262B2 (en) 2003-01-29 2008-04-15 Whitehead Institute For Biomedical Research Identification of genotype-selective anti-tumor agents
WO2004073619A2 (en) 2003-02-14 2004-09-02 Smithkline Beecham Corporation Ccr8 antagonists
WO2004074438A2 (en) 2003-02-14 2004-09-02 Smithkline Beecham Corporation Ccr8 antagonists
WO2005035507A2 (en) 2003-10-10 2005-04-21 Bayer Pharmaceuticals Corporation 4-aminopyrimidine derivatives for treatment of hyperproliferative disorders
US20070196395A1 (en) 2003-12-12 2007-08-23 Mackerell Alexander Immunomodulatory compounds that target and inhibit the py'binding site of tyrosene kinase p56 lck sh2 domain
AU2004312049A1 (en) 2003-12-24 2005-07-21 Scios, Inc. Treatment of malignant gliomas with TFG-beta inhibitors
AU2005286592A1 (en) 2004-09-23 2006-03-30 Reddy Us Therapeutics, Inc. Novel pyrimidine compounds, process for their preparation and compositions containing them
US20100160324A1 (en) 2004-12-30 2010-06-24 Astex Therapeutics Limited Pyrazole derivatives as that modulate the activity of cdk, gsk and aurora kinases
EP1924573A1 (en) 2005-01-25 2008-05-28 AstraZeneca AB B-raf inhibitors
CA2611728A1 (en) 2005-06-08 2006-12-14 Millennium Pharmaceuticals, Inc. Methods for the identification, assessment, and treatment of patients with cancer therapy
EP1917252B1 (en) 2005-08-26 2014-01-01 Merck Serono SA Pyrazine derivatives and use as pi3k inhibitors
US8133900B2 (en) 2005-11-01 2012-03-13 Targegen, Inc. Use of bi-aryl meta-pyrimidine inhibitors of kinases
TW200815426A (en) 2006-06-28 2008-04-01 Astrazeneca Ab New pyridine analogues II 333
CN101679371A (zh) 2006-12-04 2010-03-24 艾美罗股份公司 作为腺苷受体拮抗剂的取代的嘧啶
WO2008076883A2 (en) 2006-12-15 2008-06-26 Abraxis Bioscience, Inc. Triazine derivatives and their therapeutical applications
JP5450381B2 (ja) * 2007-04-30 2014-03-26 プロメティック・バイオサイエンスィズ・インコーポレーテッド 化合物、そのような化合物を含有する組成物、及びそのような化合物を用いるがん及び自己免疫疾患の治療法
CA2683152A1 (en) 2007-06-11 2008-12-18 Miikana Therapeutics, Inc. Substituted pyrazole compounds
NZ583450A (en) 2007-07-20 2012-05-25 Nerviano Medical Sciences Srl Substituted indazole derivatives active as kinase inhibitors
WO2009027736A2 (en) * 2007-08-27 2009-03-05 Astrazeneca Ab 2,4 diaminopyrimid'lnes for the treatment of myeloproliferative disorders and cancer
BRPI0818366A2 (pt) 2007-10-10 2015-04-07 Takeda Pharmaceutical Composto, pró-droga, medicamento, método inibidor de faah, métodos de profilaxia ou tratamento para ansiedade, ou depressão, ou de alívio da dor, e de profilaxia ou tratamento para dor inflamatória ou dor neuropática, e, uso do composto.
AU2008345225A1 (en) 2007-12-21 2009-07-09 University Of Rochester Method for altering the lifespan of eukaryotic organisms
GB0805477D0 (en) 2008-03-26 2008-04-30 Univ Nottingham Pyrimidines triazines and their use as pharmaceutical agents
JP5277685B2 (ja) 2008-03-26 2013-08-28 富士ゼロックス株式会社 電子写真感光体、画像形成装置、プロセスカートリッジ及び画像形成方法
CN101575408B (zh) 2008-05-09 2013-10-30 Mca技术有限公司 用作阻燃剂和光稳定剂的聚三嗪基化合物
FR2932483A1 (fr) 2008-06-13 2009-12-18 Cytomics Systems Composes utiles pour le traitement des cancers.
WO2010007756A1 (ja) 2008-07-14 2010-01-21 塩野義製薬株式会社 Ｔｔｋ阻害作用を有するピリジン誘導体
AU2009288004B2 (en) 2008-09-03 2015-02-05 Duke University Genetic alterations in isocitrate dehydrogenase and other genes in malignant glioma
US20100144722A1 (en) 2008-09-03 2010-06-10 Dr. Reddy's Laboratories Ltd. Novel heterocyclic compounds as gata modulators
JP2010079130A (ja) 2008-09-29 2010-04-08 Fuji Xerox Co Ltd 電子写真感光体、プロセスカートリッジ、及び画像形成装置
JP2010181540A (ja) 2009-02-04 2010-08-19 Fuji Xerox Co Ltd 電子写真感光体、プロセスカートリッジ、及び画像形成装置
JP5263304B2 (ja) * 2009-02-06 2013-08-14 日本新薬株式会社 アミノピラジン誘導体及び医薬
CN102985557B (zh) 2009-03-13 2018-06-15 安吉奥斯医药品有限公司 用于细胞增殖相关病症的方法和组合物
US8261872B2 (en) 2009-06-08 2012-09-11 Clark Equipment Company Work machine having modular ignition switch keypad with latching output
US20120238576A1 (en) 2009-06-08 2012-09-20 California Capital Equity, Llc Triazine Derivatives and their Therapeutical Applications
WO2010144404A1 (en) 2009-06-09 2010-12-16 Abraxis Bioscience, Llc Pyridil-triazine inhibitors of hedgehog signaling
BRPI1011527A2 (pt) 2009-06-09 2016-07-26 California Capital Equity Llc derivados de triazina substituídos com ureidofenil e suas aplicações terapêuticas.
WO2011005208A1 (en) 2009-07-10 2011-01-13 Milux Holding S.A. Knee joint device and method
JP5473851B2 (ja) 2009-09-30 2014-04-16 富士フイルム株式会社 高分子フィルム、位相差フィルム、偏光板及び液晶表示装置
WO2011050210A1 (en) 2009-10-21 2011-04-28 Agios Pharmaceuticals, Inc. Methods and compositions for cell-proliferation-related disorders
CA2793836C (en) 2009-10-21 2020-03-24 Agios Pharmaceuticals, Inc. Methods and compositions for cell-proliferation-related disorders
ES2642109T3 (es) 2009-12-09 2017-11-15 Agios Pharmaceuticals, Inc. Compuestos terapéuticamente activos para su uso en el tratamiento de cáncer caracterizados por tener una mutación de IDH
US20130197106A1 (en) 2010-04-01 2013-08-01 Agios Pharmaceuticals, Inc Methods of identifying a candidate compound
WO2012009678A1 (en) 2010-07-16 2012-01-19 Agios Pharmaceuticals, Inc. Therapeutically active compositions and their method of use
JP5907986B2 (ja) 2010-11-29 2016-04-26 ガリオン ファーマシューティカルズ インコーポレイテッド 呼吸制御障害または呼吸制御疾患の処置用の呼吸刺激薬としての化合物
TWI555737B (zh) 2011-05-24 2016-11-01 拜耳知識產權公司 含有硫醯亞胺基團之４－芳基－ｎ－苯基－１，３，５－三氮雜苯－２－胺
CN102827170A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN102827073A (zh) 2011-06-17 2012-12-19 安吉奥斯医药品有限公司 治疗活性组合物和它们的使用方法
CN102659765B (zh) 2011-12-31 2014-09-10 沈阳药科大学 嘧啶及三嗪类化合物的制备方法和应用
CN115521264A (zh) * 2012-01-06 2022-12-27 法国施维雅药厂 治疗活性化合物及其使用方法
AU2013207252B2 (en) 2012-01-06 2016-06-09 H.Lundbeck A/S Carbamate compounds and pharmaceutical compositions thereof
MX350432B (es) 2012-01-19 2017-09-06 Agios Pharmaceuticals Inc Compuestos terapeuticamente activos y sus metodos de empleo.
US9474779B2 (en) 2012-01-19 2016-10-25 Agios Pharmaceuticals, Inc. Therapeutically active compositions and their methods of use
US20150011751A1 (en) 2012-03-09 2015-01-08 Carna Biosciences, Inc. Novel triazine derivative
US9579324B2 (en) 2013-07-11 2017-02-28 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use
US20150031627A1 (en) 2013-07-25 2015-01-29 Agios Pharmaceuticals, Inc Therapeutically active compounds and their methods of use

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