AU2015369712B2 - Mutant IDH1 inhibitors useful for treating cancer - Google Patents
Mutant IDH1 inhibitors useful for treating cancer Download PDFInfo
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- AU2015369712B2 AU2015369712B2 AU2015369712A AU2015369712A AU2015369712B2 AU 2015369712 B2 AU2015369712 B2 AU 2015369712B2 AU 2015369712 A AU2015369712 A AU 2015369712A AU 2015369712 A AU2015369712 A AU 2015369712A AU 2015369712 B2 AU2015369712 B2 AU 2015369712B2
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- 0 CC(C)(C1)CC(N(c2cc(OC)ccc2OC)C(C(C=N*)=C2)=O)=C2C1=O Chemical compound CC(C)(C1)CC(N(c2cc(OC)ccc2OC)C(C(C=N*)=C2)=O)=C2C1=O 0.000 description 2
- FEYDZHNIIMENOB-UHFFFAOYSA-N Brc1nc(Br)ccc1 Chemical compound Brc1nc(Br)ccc1 FEYDZHNIIMENOB-UHFFFAOYSA-N 0.000 description 1
- HYNQLFSSBNCYIP-UHFFFAOYSA-N CC(C)(C1)CC(N(c(cc(cc2)OC)c2OC)C(C(C#N)=C2)=O)=C2C1=O Chemical compound CC(C)(C1)CC(N(c(cc(cc2)OC)c2OC)C(C(C#N)=C2)=O)=C2C1=O HYNQLFSSBNCYIP-UHFFFAOYSA-N 0.000 description 1
- CXATVVLZNJMUJA-UHFFFAOYSA-N CC(C)(C1)CC(N(c2cc(OC)ccc2OC)C(C(c2n[n](-c(cc3)ccc3Cl)nn2)=C2)=O)=C2C1=O Chemical compound CC(C)(C1)CC(N(c2cc(OC)ccc2OC)C(C(c2n[n](-c(cc3)ccc3Cl)nn2)=C2)=O)=C2C1=O CXATVVLZNJMUJA-UHFFFAOYSA-N 0.000 description 1
- CFKQYZQIWGUIBD-UHFFFAOYSA-N CC(C)(C1)CC(N(c2cc(OC)ccc2OC)C(C(c2nc(-c(cc3)ccc3Cl)n[o]2)=C2)=O)=C2C1=O Chemical compound CC(C)(C1)CC(N(c2cc(OC)ccc2OC)C(C(c2nc(-c(cc3)ccc3Cl)n[o]2)=C2)=O)=C2C1=O CFKQYZQIWGUIBD-UHFFFAOYSA-N 0.000 description 1
- UMZODYOZUBWCCB-UHFFFAOYSA-N CC(C)(CC(C1)=O)OC1=O Chemical compound CC(C)(CC(C1)=O)OC1=O UMZODYOZUBWCCB-UHFFFAOYSA-N 0.000 description 1
- NAUKVLRFGMDIAN-UHFFFAOYSA-N CC(c1cnc(C(F)(F)F)cc1)=O Chemical compound CC(c1cnc(C(F)(F)F)cc1)=O NAUKVLRFGMDIAN-UHFFFAOYSA-N 0.000 description 1
- PAQZWJGSJMLPMG-UHFFFAOYSA-N CCCP(OP(CCC)(O1)=O)(OP1(CCC)=O)=O Chemical compound CCCP(OP(CCC)(O1)=O)(OP1(CCC)=O)=O PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 1
- CTTFKYNTEXGSOY-UHFFFAOYSA-N CCc(cccc1CC)c1N(C(C=C(C)C)=C(C=C1c2nc(-c3ccc(C(F)(F)F)cc3)c[s]2)C(N2CCNCC2)=O)C1=O Chemical compound CCc(cccc1CC)c1N(C(C=C(C)C)=C(C=C1c2nc(-c3ccc(C(F)(F)F)cc3)c[s]2)C(N2CCNCC2)=O)C1=O CTTFKYNTEXGSOY-UHFFFAOYSA-N 0.000 description 1
- DUIGVOTUYOPPDL-UHFFFAOYSA-N CCc(cccc1CC)c1N(C(CC(C)(C)O1)=C(C=C2c3nc(-c4cnc(C(F)(F)F)cc4)c[s]3)C1=O)C2=O Chemical compound CCc(cccc1CC)c1N(C(CC(C)(C)O1)=C(C=C2c3nc(-c4cnc(C(F)(F)F)cc4)c[s]3)C1=O)C2=O DUIGVOTUYOPPDL-UHFFFAOYSA-N 0.000 description 1
- ZSXGLVDWWRXATF-UHFFFAOYSA-N CN(C)C(OC)OC Chemical compound CN(C)C(OC)OC ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 1
- NAZDVUBIEPVUKE-UHFFFAOYSA-N COc(cc1)cc(N)c1OC Chemical compound COc(cc1)cc(N)c1OC NAZDVUBIEPVUKE-UHFFFAOYSA-N 0.000 description 1
- JZUWTQJWKPQEEA-UHFFFAOYSA-N COc(cc1)cc(O)c1N(C=CC=C1c2nc(-c(cc3)ccc3Cl)c[s]2)C1=O Chemical compound COc(cc1)cc(O)c1N(C=CC=C1c2nc(-c(cc3)ccc3Cl)c[s]2)C1=O JZUWTQJWKPQEEA-UHFFFAOYSA-N 0.000 description 1
- OMFADRDKJLTAAO-UHFFFAOYSA-N COc(cc1NC(Cc2nc(-c(cc3)ccc3Cl)c[s]2)=O)ccc1OC Chemical compound COc(cc1NC(Cc2nc(-c(cc3)ccc3Cl)c[s]2)=O)ccc1OC OMFADRDKJLTAAO-UHFFFAOYSA-N 0.000 description 1
- INSUOBTXFMTQFQ-UHFFFAOYSA-N N#CC[n]1cnc(-c2ccccc2)c1 Chemical compound N#CC[n]1cnc(-c2ccccc2)c1 INSUOBTXFMTQFQ-UHFFFAOYSA-N 0.000 description 1
- WOSRIYRLFLMNQC-UHFFFAOYSA-N N#CCc1nc(-c2ccc(C(F)(F)F)nc2)c[s]1 Chemical compound N#CCc1nc(-c2ccc(C(F)(F)F)nc2)c[s]1 WOSRIYRLFLMNQC-UHFFFAOYSA-N 0.000 description 1
- GCOTWHHKZPEEEV-UHFFFAOYSA-N N#CCc1nc(cc(cc2)Cl)c2[s]1 Chemical compound N#CCc1nc(cc(cc2)Cl)c2[s]1 GCOTWHHKZPEEEV-UHFFFAOYSA-N 0.000 description 1
- QBGONPQFBDUVPG-UHFFFAOYSA-N N/C(/c(cc1)ccc1Cl)=N\O Chemical compound N/C(/c(cc1)ccc1Cl)=N\O QBGONPQFBDUVPG-UHFFFAOYSA-N 0.000 description 1
- QSNSCYSYFYORTR-UHFFFAOYSA-N Nc(cc1)ccc1Cl Chemical compound Nc(cc1)ccc1Cl QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 1
- OJEJYGUDWWJGKL-UHFFFAOYSA-N O=C(CBr)c1cnc(C(F)(F)F)cc1 Chemical compound O=C(CBr)c1cnc(C(F)(F)F)cc1 OJEJYGUDWWJGKL-UHFFFAOYSA-N 0.000 description 1
- XDQYQPSLBRLERC-UHFFFAOYSA-N OC(Cc1nc(-c(cc2)ccc2Cl)c[s]1)=O Chemical compound OC(Cc1nc(-c(cc2)ccc2Cl)c[s]1)=O XDQYQPSLBRLERC-UHFFFAOYSA-N 0.000 description 1
- XHLKOHSAWQPOFO-UHFFFAOYSA-N c1c(-c2ccccc2)nc[nH]1 Chemical compound c1c(-c2ccccc2)nc[nH]1 XHLKOHSAWQPOFO-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
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- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
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- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
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- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
- C07D491/048—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being five-membered
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C07D491/044—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/10—Spiro-condensed systems
- C07D491/107—Spiro-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring
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| SI3447050T1 (sl) | 2014-09-19 | 2020-08-31 | Forma Therapeutics, Inc. | Derivati piridin-2(1H)-on kinolinona kot inhibitorji mutirane izocitratne dehidrogenaze |
| WO2016044782A1 (en) | 2014-09-19 | 2016-03-24 | Forma Therapeutics, Inc. | Phenyl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors |
| CA2961793C (en) | 2014-09-19 | 2021-03-16 | Forma Therapeutics, Inc. | Quinolinone pyrimidines compositions as mutant-isocitrate dehydrogenase inhibitors |
| US10328064B2 (en) | 2014-12-23 | 2019-06-25 | Fgh Biotech, Inc. | Compositions of fatostatin based heterocyclic compounds and uses thereof |
| US9624216B2 (en) | 2015-04-21 | 2017-04-18 | Forma Therapeutics, Inc. | Quinolinone five-membered heterocyclic compounds as mutant-isocitrate dehydrogenase inhibitors |
| US10294206B2 (en) | 2015-04-21 | 2019-05-21 | Forma Tm2, Inc. | Fused-bicyclic aryl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors |
| MX382630B (es) | 2016-04-29 | 2025-03-13 | Fgh Biotech Inc | Compuestos de pirazol disustituidos para el tratamiento de enfermedades. |
| CN109641887B (zh) * | 2016-06-22 | 2022-09-20 | 美国政府健康及人类服务部 | 可用作用于治疗癌症的突变idh1抑制剂的噻唑衍生物 |
| EP3510027B1 (en) * | 2016-09-07 | 2022-11-02 | FGH BioTech, Inc. | Di-substituted pyrazole compounds for the treatment of diseases |
| WO2019146129A1 (ja) * | 2018-01-29 | 2019-08-01 | 富士フイルム株式会社 | イソクエン酸デヒドロゲナーゼ変異を有する腫瘍に対する医薬組成物および抗腫瘍剤ならびにその利用 |
| US11576906B2 (en) | 2018-05-16 | 2023-02-14 | Forma Therapeutics, Inc. | Inhibiting mutant IDH-1 |
| 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) |
| US11013733B2 (en) | 2018-05-16 | 2021-05-25 | Forma Therapeutics, Inc. | Inhibiting mutant isocitrate dehydrogenase 1 (mlDH-1) |
| US11013734B2 (en) | 2018-05-16 | 2021-05-25 | Forma Therapeutics, Inc. | Treating patients harboring an isocitrate dehydrogenase-1 (IDH-1) mutation |
| JP7258059B2 (ja) * | 2018-06-26 | 2023-04-14 | 昆薬集団股▲フン▼有限公司 | ベンズイミダゾール誘導体及びそのidh1阻害剤としての応用 |
| CN109224061B (zh) * | 2018-11-16 | 2022-01-07 | 上海市肺科医院 | 化合物ag120或其药学上可接受的盐在制备预防或治疗结核病的药物中的用途 |
| US12014835B2 (en) | 2020-02-19 | 2024-06-18 | Vanderbilt University | Methods for evaluating therapeutic benefit of combination therapies |
| KR20250121123A (ko) | 2022-12-16 | 2025-08-11 | 카루나 세러퓨틱스 인코포레이티드 | 치환된 테트라히드로피롤로-피리디논 화합물 및 의학적 병태를 치료하는 데 있어서의 이의 용도 |
| CN116284025B (zh) * | 2023-02-20 | 2025-07-04 | 国科大杭州高等研究院 | 一种具有抗癌作用的螺杂环类化合物、药物组合物及其用途 |
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| CN1774247A (zh) * | 2003-02-14 | 2006-05-17 | 史密丝克莱恩比彻姆公司 | 新的化合物 |
| EP1871368B1 (en) | 2005-04-04 | 2011-06-08 | Eisai R&D Management Co., Ltd. | Dihydropyridine compounds for neurodegenerative diseases and dementia |
| WO2007053610A2 (en) | 2005-11-01 | 2007-05-10 | The Regents Of The University Of California | Methods of treating atrial fibrillation wtih pirfenidone |
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| WO2008011109A2 (en) * | 2006-07-20 | 2008-01-24 | Amgen Inc. | Substituted pyridone compounds and methods of use |
| US8188113B2 (en) | 2006-09-14 | 2012-05-29 | Deciphera Pharmaceuticals, Inc. | Dihydropyridopyrimidinyl, dihydronaphthyidinyl and related compounds useful as kinase inhibitors for the treatment of proliferative diseases |
| WO2008079316A1 (en) | 2006-12-20 | 2008-07-03 | Cara Therapeutics, Inc. | Tetrahydroquinolinones, tetrahydronaphthyridones and derivatives thereof |
| US20100256191A1 (en) | 2007-12-26 | 2010-10-07 | Eisai R&D Management Co., Ltd. | Ampa receptor antagonists and zonisamide for epilepsy |
| ES2812537T3 (es) * | 2009-10-21 | 2021-03-17 | Agios Pharmaceuticals Inc | Métodos y composiciones para trastornos relacionados con la proliferación celular |
| EP3561077B1 (en) | 2009-10-21 | 2022-12-21 | Les Laboratoires Servier | Methods for cell-proliferation-related disorders |
| JP5967827B2 (ja) | 2009-12-09 | 2016-08-10 | 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 | Idh変異体をもつことを特徴とする癌治療用の治療的活性化合物 |
| CN103097340B (zh) | 2010-07-16 | 2018-03-16 | 安吉奥斯医药品有限公司 | 治疗活性组合物及其使用方法 |
| CN103608346B (zh) | 2011-02-02 | 2016-06-15 | 菲布罗根有限公司 | 作为缺氧诱导因子(hif)羟化酶抑制剂的萘啶衍生物 |
| 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 |
| MX342326B (es) | 2011-09-27 | 2016-09-26 | Novartis Ag | 3-pirimidin-4-il-oxazolidin-2-onas como inhibidoras de idh mutante. |
| WO2013130855A1 (en) | 2012-03-02 | 2013-09-06 | Takeda Pharmaceutical Company Limited | Indazole derivatives |
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Non-Patent Citations (1)
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| BAISONG ZHENG ET AL, "Crystallographic Investigation and Selective Inhibition of Mutant Isocitrate Dehydrogenase", ACS MEDICINAL CHEMISTRY LETTERS, (2013-06-13), vol. 4, no. 6, doi:10.1021/ml400036z, ISSN 1948-5875, pages 542 - 546 * |
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| EP3237385A1 (en) | 2017-11-01 |
| JP2018500360A (ja) | 2018-01-11 |
| EP3237385B1 (en) | 2021-11-24 |
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| WO2016106331A8 (en) | 2016-09-29 |
| CN107428690A (zh) | 2017-12-01 |
| JP6901394B2 (ja) | 2021-07-14 |
| US10703746B2 (en) | 2020-07-07 |
| CA2971872C (en) | 2023-10-10 |
| CN107428690B (zh) | 2021-04-13 |
| ES2905564T3 (es) | 2022-04-11 |
| US20190071434A1 (en) | 2019-03-07 |
| WO2016106331A1 (en) | 2016-06-30 |
| AU2015369712A1 (en) | 2017-07-20 |
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