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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- C07D451/00—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
- 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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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
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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
- C07D491/052—Ortho-condensed systems with only one oxygen atom as ring hetero atom in the oxygen-containing ring the oxygen-containing ring being six-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
- C07D491/10—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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| US9771349B2 (en) | 2014-09-19 | 2017-09-26 | Forma Therapeutics, Inc. | Pyridinyl quinolinone derivatives as mutant-isocitrate dehydrogenase inhibitors |
| ES2768694T3 (es) | 2014-09-19 | 2020-06-23 | Forma Therapeutics Inc | Composiciones de quinolinona pirimidinas como inhibidores de isocitrato dehidrogenasa mutante |
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| TW201932120A (zh) * | 2018-01-29 | 2019-08-16 | 日商富士軟片股份有限公司 | 用於具有異檸檬酸脫氫酶突變的腫瘤的藥物組成物與抗腫瘤劑及其應用 |
| 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 |
| 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) |
| WO2020001474A1 (zh) * | 2018-06-26 | 2020-01-02 | 南京明德新药研发有限公司 | 苯并咪唑衍生物及其作为idh1抑制剂的应用 |
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| 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 |
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| US8921389B2 (en) | 2011-02-02 | 2014-12-30 | Fibrogen, Inc. | Naphthyridine derivatives as inhibitors of hypoxia inducible factor (HIF) hydroxylase |
| 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 |
| JP6026544B2 (ja) | 2011-09-27 | 2016-11-16 | ノバルティス アーゲー | 変異体idhの阻害剤としての3−ピリミジン−4−イル−オキサゾリジン−2−オン類 |
| US9434743B2 (en) * | 2012-03-02 | 2016-09-06 | Takeda Pharmaceutical Company Limited | Indazole derivatives |
| PT3733662T (pt) | 2014-09-19 | 2023-08-18 | Forma Therapeutics Inc | Derivados piridin-2(1h)-ona-quinolinona como inibidores de isocitrato desidrogenase mutante |
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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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