BR112013001122B1 - composto de fórmula ii, uso do composto e composição farmacêutica compreendendo dito composto - Google Patents
composto de fórmula ii, uso do composto e composição farmacêutica compreendendo dito composto Download PDFInfo
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- BR112013001122B1 BR112013001122B1 BR112013001122-0A BR112013001122A BR112013001122B1 BR 112013001122 B1 BR112013001122 B1 BR 112013001122B1 BR 112013001122 A BR112013001122 A BR 112013001122A BR 112013001122 B1 BR112013001122 B1 BR 112013001122B1
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- mhz
- nmr
- dmso
- ylmethyl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 498
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 18
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 title description 3
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 82
- 201000011510 cancer Diseases 0.000 claims abstract description 62
- 102100039905 Isocitrate dehydrogenase [NADP] cytoplasmic Human genes 0.000 claims abstract description 36
- 101000960234 Homo sapiens Isocitrate dehydrogenase [NADP] cytoplasmic Proteins 0.000 claims abstract description 33
- 101001042041 Bos taurus Isocitrate dehydrogenase [NAD] subunit beta, mitochondrial Proteins 0.000 claims abstract description 31
- -1 3,3-difluorocyclobutyl Chemical group 0.000 claims description 233
- 238000011282 treatment Methods 0.000 claims description 35
- 238000002360 preparation method Methods 0.000 claims description 31
- 230000035772 mutation Effects 0.000 claims description 27
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Chemical group 0.000 claims description 19
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 14
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 14
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 14
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- 102200069690 rs121913500 Human genes 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 10
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 8
- 239000011737 fluorine Chemical group 0.000 claims description 7
- 229910052731 fluorine Inorganic materials 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 6
- 125000000980 1H-indol-3-ylmethyl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C(C([H])([H])[*])C2=C1[H] 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 229910052794 bromium Chemical group 0.000 claims description 3
- 229910052801 chlorine Inorganic materials 0.000 claims description 3
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- BVCRERJDOOBZOH-UHFFFAOYSA-N bicyclo[2.2.1]heptanyl Chemical group C1C[C+]2CC[C-]1C2 BVCRERJDOOBZOH-UHFFFAOYSA-N 0.000 claims description 2
- 238000000338 in vitro Methods 0.000 claims 3
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- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 700
- 238000005160 1H NMR spectroscopy Methods 0.000 description 410
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
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- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 12
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Classifications
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| TWI598337B (zh) | 2009-06-29 | 2017-09-11 | 阿吉歐斯製藥公司 | 治療化合物及組成物 |
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| EP2525790B1 (en) | 2009-10-21 | 2020-05-27 | Agios Pharmaceuticals, Inc. | Methods and compositions for cell-proliferation-related disorders |
| SMT202400081T1 (it) | 2011-05-03 | 2024-03-13 | Agios Pharmaceuticals Inc | Attivatori della piruvato chinasi per uso in terapia |
| 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 |
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| BR112014007310A2 (pt) | 2011-09-27 | 2017-04-04 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inibidores de idh mutante |
| MX2014006072A (es) * | 2011-11-25 | 2014-08-08 | Bayer Ip Gmbh | Derivados de 2-yodo-imidazol. |
| US9877962B2 (en) | 2011-12-30 | 2018-01-30 | Marc Henry Pitty | Piperazinyl derivatives for the treatment of cancer |
| FR2985256B1 (fr) * | 2011-12-30 | 2016-03-04 | Pitty Marc Henry | Derives piperazinyles pour le traitement de cancers |
| PE20142098A1 (es) | 2012-01-06 | 2015-01-08 | Agios Pharmaceuticals Inc | Compuestos terapeuticamente activos y sus metodos de uso |
| US9474779B2 (en) | 2012-01-19 | 2016-10-25 | Agios Pharmaceuticals, Inc. | Therapeutically active compositions and their methods of use |
| US20150087600A1 (en) * | 2012-01-19 | 2015-03-26 | Agios Pharmaceuticals, Inc | Therapeutically active compounds and their methods of use |
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| US20150038541A1 (en) * | 2012-03-19 | 2015-02-05 | Aposignal Bioscience Llc | Composition and methods for cell modulation |
| EP2906212A4 (en) | 2012-10-15 | 2016-06-08 | Agios Pharmaceuticals Inc | THERAPEUTIC COMPOUNDS AND COMPOSITIONS |
| US9296733B2 (en) | 2012-11-12 | 2016-03-29 | Novartis Ag | Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases |
| TWI637951B (zh) | 2013-02-15 | 2018-10-11 | 英商葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之雜環醯胺類 |
| GEP201606600B (en) | 2013-02-22 | 2017-01-10 | Pfizer | Pyrrolo [2, 3 -d]pyrimidine derivatives as inhibitors of janus- related kinases (jak) |
| JP6387360B2 (ja) | 2013-03-14 | 2018-09-05 | ノバルティス アーゲー | 変異idhの阻害薬としての3−ピリミジン−4−イル−オキサゾリジン−2−オン |
| WO2014184272A2 (en) * | 2013-05-14 | 2014-11-20 | Medizinische Hochschule Hannover | Means and methods for treating cancer |
| AU2014287122B9 (en) | 2013-07-11 | 2018-11-01 | Les Laboratoires Servier | N,6-bis(aryl or heteroaryl)-1,3,5-triazine-2,4-diamine compounds as IDH2 mutants inhibitors for the treatment of cancer |
| CN105593215B (zh) | 2013-07-11 | 2019-01-15 | 安吉奥斯医药品有限公司 | 用于治疗癌症的作为idh2突变体抑制剂的2,4-或4,6-二氨基嘧啶化合物 |
| WO2015003360A2 (en) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
| WO2015003355A2 (en) | 2013-07-11 | 2015-01-15 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
| WO2015010297A1 (en) * | 2013-07-25 | 2015-01-29 | Agios Pharmaceuticals, Inc. | Therapeutically active compounds and their methods of use |
| KR101861869B1 (ko) * | 2013-09-10 | 2018-05-28 | 경희대학교 산학협력단 | 신규한 비스-아미드 유도체 및 이의 용도 |
| NZ723859A (en) | 2014-03-14 | 2023-01-27 | Servier Lab | Pharmaceutical compositions of therapeutically active compounds and their uses |
| WO2016024185A1 (en) | 2014-08-12 | 2016-02-18 | Pfizer Inc. | Pyrrolo[2,3-d]pyrimidine derivatives useful for inhibiting janus kinase |
| BR112017006425B8 (pt) * | 2014-10-01 | 2023-05-16 | Daiichi Sankyo Co Ltd | Compostos derivados de isoxazol, seus usos, inibidores de isocitrato desidrogenase 1 mutante e da produção de d-2 hidroxiglutamato, agente antitumoral e composição farmacêutica compreendendo os mesmos |
| JP6672288B2 (ja) * | 2014-10-23 | 2020-03-25 | バイエル・ファルマ・アクティエンゲゼルシャフト | 腫瘍の治療のためのmidh1阻害剤としての1−シクロヘキシル−2−フェニルアミノベンゾイミダゾール |
| AU2015369712B2 (en) | 2014-12-22 | 2020-05-07 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Mutant IDH1 inhibitors useful for treating cancer |
| CA2989111C (en) | 2015-06-11 | 2023-10-03 | Agios Pharmaceuticals, Inc. | Methods of using pyruvate kinase activators |
| JP6824954B2 (ja) * | 2015-07-16 | 2021-02-03 | ドイチェス クレープスフォルシュングスツェントルム シュティフトゥング デス エッフェントリッヒェン レヒツ | mIDH1阻害剤としての5−ヒドロキシアルキルベンズイミダゾール |
| FI3362065T3 (fi) | 2015-10-15 | 2024-06-19 | Servier Lab | Ivosidenibiä, sytarabiinia ja daunorubisiinia tai idarubisiinia käsittävä yhdistelmähoito akuutin myelooisen leukemian hoitamiseksi |
| KR102699521B1 (ko) | 2015-10-15 | 2024-08-26 | 르 라보레또레 쎄르비에르 | 악성 종양의 치료를 위한 조합물 요법 |
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| GB201721964D0 (en) | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
| GB201721960D0 (en) | 2017-12-27 | 2018-02-07 | Bp Oil Int | Methods for preparing fuel additives |
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| CN110283096A (zh) * | 2019-07-03 | 2019-09-27 | 三峡大学 | 一种Cu-MOF催化的ɑ-胺基酰胺类化合物及其制备方法 |
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| WO2022221686A1 (en) * | 2021-04-15 | 2022-10-20 | Pardes Biosciences, Inc. | Inhibitors of cysteine proteases and methods of use thereof |
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| WO2001016097A1 (en) * | 1999-08-27 | 2001-03-08 | Sugen, Inc. | Phosphate mimics and methods of treatment using phosphatase inhibitors |
| US20040067234A1 (en) * | 2002-07-11 | 2004-04-08 | Paz Einat | Isocitrate dehydrogenase and uses thereof |
| CN101137414A (zh) * | 2004-12-31 | 2008-03-05 | 欧兰拓制药股份有限公司 | 多环双酰胺mmp抑制剂 |
| WO2009086303A2 (en) * | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| FR2932483A1 (fr) * | 2008-06-13 | 2009-12-18 | Cytomics Systems | Composes utiles pour le traitement des cancers. |
| US8685660B2 (en) * | 2008-09-03 | 2014-04-01 | The Johns Hopkins University | Genetic alterations in isocitrate dehydrogenase and other genes in malignant glioma |
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2011
- 2011-07-15 CN CN201180043254.6A patent/CN103097340B/zh active Active
- 2011-07-15 EP EP11738902.3A patent/EP2593425B1/en active Active
- 2011-07-15 AU AU2011278998A patent/AU2011278998B2/en active Active
- 2011-07-15 CA CA2805669A patent/CA2805669C/en active Active
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- 2011-07-15 MX MX2013000614A patent/MX342951B/es active IP Right Grant
- 2011-07-15 US US13/810,410 patent/US20130184222A1/en not_active Abandoned
- 2011-07-15 JP JP2013519858A patent/JP6081354B2/ja active Active
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| CA2805669A1 (en) | 2012-01-19 |
| EP2593425B1 (en) | 2018-10-17 |
| MX2013000614A (es) | 2013-06-28 |
| MX342951B (es) | 2016-10-18 |
| BR112013001122A2 (pt) | 2017-07-11 |
| WO2012009678A8 (en) | 2012-03-29 |
| US20160264621A1 (en) | 2016-09-15 |
| AU2011278998B2 (en) | 2016-06-09 |
| CN103097340A (zh) | 2013-05-08 |
| JP2013536168A (ja) | 2013-09-19 |
| US20130184222A1 (en) | 2013-07-18 |
| ES2704862T3 (es) | 2019-03-20 |
| WO2012009678A1 (en) | 2012-01-19 |
| JP6081354B2 (ja) | 2017-02-15 |
| EP2593425A1 (en) | 2013-05-22 |
| JP2017039725A (ja) | 2017-02-23 |
| CA2805669C (en) | 2018-08-21 |
| CN103097340B (zh) | 2018-03-16 |
| AU2011278998A1 (en) | 2013-01-31 |
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