AU2017217536A1 - Inhibitor of indoleamine-2,3-dioxygenase (IDO) - Google Patents
Inhibitor of indoleamine-2,3-dioxygenase (IDO) Download PDFInfo
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- AU2017217536A1 AU2017217536A1 AU2017217536A AU2017217536A AU2017217536A1 AU 2017217536 A1 AU2017217536 A1 AU 2017217536A1 AU 2017217536 A AU2017217536 A AU 2017217536A AU 2017217536 A AU2017217536 A AU 2017217536A AU 2017217536 A1 AU2017217536 A1 AU 2017217536A1
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- Prior art keywords
- substituted
- unsubstituted
- compound
- alkyl
- cancer
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 102000006639 indoleamine 2,3-dioxygenase Human genes 0.000 title description 41
- 108020004201 indoleamine 2,3-dioxygenase Proteins 0.000 title description 41
- 239000003112 inhibitor Substances 0.000 title description 9
- 150000001875 compounds Chemical class 0.000 claims abstract description 204
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 58
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 56
- 201000010099 disease Diseases 0.000 claims abstract description 54
- 238000000034 method Methods 0.000 claims abstract description 45
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- 201000011510 cancer Diseases 0.000 claims abstract description 27
- 208000035473 Communicable disease Diseases 0.000 claims abstract description 10
- 208000015181 infectious disease Diseases 0.000 claims abstract description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 90
- 125000003118 aryl group Chemical group 0.000 claims description 70
- 125000000304 alkynyl group Chemical group 0.000 claims description 53
- 125000001072 heteroaryl group Chemical group 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 239000001257 hydrogen Substances 0.000 claims description 40
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 32
- 229910052736 halogen Inorganic materials 0.000 claims description 23
- 150000002367 halogens Chemical class 0.000 claims description 23
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 21
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 19
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 19
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000002950 monocyclic group Chemical group 0.000 claims description 14
- 125000002619 bicyclic group Chemical group 0.000 claims description 13
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- 125000004093 cyano group Chemical group *C#N 0.000 claims description 12
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
- 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 12
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 11
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- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 8
- 238000011319 anticancer therapy Methods 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
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- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 5
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- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
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- 125000003627 8 membered carbocyclic group Chemical group 0.000 claims description 3
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- 201000010881 cervical cancer Diseases 0.000 claims description 3
- 201000004101 esophageal cancer Diseases 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 238000001959 radiotherapy Methods 0.000 claims description 3
- 125000004008 6 membered carbocyclic group Chemical group 0.000 claims description 2
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 201000005202 lung cancer Diseases 0.000 claims description 2
- 208000020816 lung neoplasm Diseases 0.000 claims description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 2
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- 150000002431 hydrogen Chemical class 0.000 claims 7
- 230000000840 anti-viral effect Effects 0.000 claims 2
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- 125000000217 alkyl group Chemical group 0.000 description 181
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- 238000003786 synthesis reaction Methods 0.000 description 130
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 81
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 67
- 125000004432 carbon atom Chemical group C* 0.000 description 63
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- 125000005842 heteroatom Chemical group 0.000 description 54
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- 238000005160 1H NMR spectroscopy Methods 0.000 description 51
- 125000004452 carbocyclyl group Chemical group 0.000 description 50
- 125000003342 alkenyl group Chemical group 0.000 description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 49
- 239000003480 eluent Substances 0.000 description 47
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 39
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 39
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 33
- 229910052757 nitrogen Inorganic materials 0.000 description 33
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 32
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 27
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- C—CHEMISTRY; METALLURGY
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- C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
- C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
- C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
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- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
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- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- 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
- C07D417/12—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 linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—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
- 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
- C07D471/08—Bridged systems
-
- C—CHEMISTRY; METALLURGY
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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- Plural Heterocyclic Compounds (AREA)
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| WO2018116108A1 (en) * | 2016-12-20 | 2018-06-28 | Glaxosmithkline Intellectual Property Development Limited | Modulators of indoleamine 2,3-dioxygenase |
| JP2020506895A (ja) | 2017-01-17 | 2020-03-05 | ボード オブ レジェンツ, ザ ユニバーシティ オブ テキサス システムBoard Of Regents, The University Of Texas System | インドールアミン2,3−ジオキシゲナーゼおよび/またはトリプトファンジオキシゲナーゼの阻害剤として有用な化合物 |
| CN110785408A (zh) * | 2017-06-28 | 2020-02-11 | 葛兰素史克知识产权开发有限公司 | 吲哚胺2,3-双加氧酶的调节剂 |
| WO2019027855A1 (en) * | 2017-08-02 | 2019-02-07 | Merck Sharp & Dohme Corp. | NOVEL SUBSTITUTED PHENYL COMPOUNDS AS INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE (IDO) |
| CN109422739B (zh) * | 2017-09-01 | 2022-07-12 | 药捷安康(南京)科技股份有限公司 | 氘代的吲哚胺2,3-双加氧酶抑制剂及其应用 |
| EP3694502B1 (en) * | 2017-10-09 | 2023-08-02 | Merck Sharp & Dohme LLC | Novel substituted cyclobutylbenzene compounds as indoleamine 2,3-dioxygenase (ido) inhibitors |
| WO2019074749A1 (en) | 2017-10-09 | 2019-04-18 | Merck Sharp & Dohme Corp. | NOVEL SUBSTITUTED CYCLOBUTYLPYRIMIDINE AND CYCLOBUTYLPYRIMIDINE COMPOUNDS AS INHIBITORS OF INDOLEAMINE 2,3-DIOXYGENASE (IDO) |
| CN109836356B (zh) * | 2017-11-24 | 2022-03-08 | 沈阳化工研究院有限公司 | 一种芳甲醚衍生物及其应用 |
| US11447449B2 (en) | 2018-01-05 | 2022-09-20 | Bristol-Myers Squibb Company | Inhibitors of indoleamine 2,3-dioxygenase and methods of their use |
| HUE066783T2 (hu) | 2018-04-18 | 2024-09-28 | Constellation Pharmaceuticals Inc | Metil módosító enzimek modulátorai, ezek készítményei és alkalmazásuk |
| CN108715585A (zh) | 2018-04-23 | 2018-10-30 | 中国药科大学 | 苯基联三氮唑类mll1-wdr5蛋白-蛋白相互作用抑制剂 |
| WO2019226491A1 (en) | 2018-05-21 | 2019-11-28 | Constellation Pharmaceuticals, Inc. | Modulators of methyl modifying enzymes, compositions and uses thereof |
| US11046649B2 (en) | 2018-07-17 | 2021-06-29 | Board Of Regents, The University Of Texas System | Compounds useful as inhibitors of indoleamine 2,3-dioxygenase and/or tryptophan dioxygenase |
| CN109734674B (zh) * | 2019-02-26 | 2022-08-26 | 中国药科大学 | 苯胺类wdr5蛋白-蛋白相互作用抑制剂及其制法和用途 |
| WO2021102618A1 (en) * | 2019-11-25 | 2021-06-03 | InventisBio Co., Ltd. | Novel salts of indoleamine 2,3-dioxygenase inhibitors |
| CN111153846B (zh) * | 2020-01-17 | 2021-08-31 | 中国药科大学 | 吡咯类化合物、其制备方法和药物组合物与用途 |
| CN114369060B (zh) * | 2020-10-15 | 2023-11-03 | 杭州星鳌生物科技有限公司 | 吲哚胺2,3-双加氧酶抑制剂及其在制备抗肿瘤药物中的应用 |
| EP4052705A1 (en) | 2021-03-05 | 2022-09-07 | Universität Basel Vizerektorat Forschung | Compositions for the treatment of ebv associated diseases or conditions |
| US20240091202A1 (en) | 2021-03-05 | 2024-03-21 | Universität Basel | Compositions for the treatment of ebv associated diseases or conditions |
| CN115594655B (zh) * | 2022-09-16 | 2023-08-15 | 桂林医学院 | 色酮肟类衍生物及其制备方法和应用 |
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| CH520667A (de) | 1967-07-22 | 1972-03-31 | Merck Patent Gmbh | Verfahren zur Herstellung von Aminophenylessigsäuren |
| GR68102B (enExample) | 1978-08-08 | 1981-10-30 | Fujisawa Pharmaceutical Co | |
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| US5852192A (en) * | 1992-03-11 | 1998-12-22 | Dr. Karl Thomae Gmbh | Cyclic urea derivatives, pharmaceutical compositions containing these compounds and processes for preparing them |
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| AU8270698A (en) | 1997-06-26 | 1999-01-19 | Eli Lilly And Company | Antithrombotic agents |
| CA2492593A1 (en) | 2002-07-15 | 2004-01-22 | Myriad Genetics, Inc. | Compounds, compositions, and methods employing same |
| JP2004203791A (ja) * | 2002-12-25 | 2004-07-22 | Dai Ichi Seiyaku Co Ltd | 芳香族化合物 |
| AU2004215359A1 (en) * | 2003-02-27 | 2004-09-10 | Abbott Laboratories | Heterocyclic kinase inhibitors |
| EA200501607A1 (ru) | 2003-04-14 | 2006-06-30 | ДЗЕ ИНСТИТЬЮТС ФОР ФАРМАСЬЮТИКАЛ ДИСКАВЕРИ, ЭлЭлСи | Замещённые фенилалкановые кислоты |
| GB0416508D0 (en) | 2004-07-23 | 2004-08-25 | Merck Sharp & Dohme | Therapeutic agents |
| CN101426774B (zh) * | 2006-04-19 | 2012-04-25 | 安斯泰来制药有限公司 | 唑类甲酰胺衍生物 |
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| BRPI1011192A2 (pt) | 2009-05-07 | 2016-03-15 | Gruenenthal Gmbh | derivados de carboxamida e ureia aromáticas substituídas como ligantes de receptor de vaniloide, composição farmacêutica, uso e processo para preparação dos referidos derivados |
| WO2010138901A1 (en) | 2009-05-29 | 2010-12-02 | Biogen Idec Ma Inc | Carboxylic acid-containing compounds, derivatives thereof, and related methods of use |
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| JP2013526546A (ja) | 2010-05-13 | 2013-06-24 | アムジエン・インコーポレーテツド | Pde10阻害剤としてのヘテロアリ−ルオキシヘテロシクリル化合物 |
| WO2012176123A1 (en) | 2011-06-22 | 2012-12-27 | Novartis Ag | 3 - imidazolyl- indoles for the treatment of proliferative diseases |
| EP2970360A4 (en) | 2013-03-13 | 2017-02-22 | Dana-Farber Cancer Institute, Inc. | Ras inhibitors and uses thereof |
| MA38483A1 (fr) * | 2013-03-15 | 2018-02-28 | Bristol Myers Squibb Co | Inhibiteurs de l'ido |
| BR112015021999A8 (pt) | 2013-03-15 | 2019-12-03 | Bristol Myers Squibb Co | inibidores de indoleamina 2,3-dioxigenase (ido), seus usos, composição farmacêutica, e método para inibir a atiavidade de indoleamina 2,3-dioxigenase |
| WO2015006520A1 (en) | 2013-07-11 | 2015-01-15 | Bristol-Myers Squibb Company | Ido inhibitors |
| JP6461948B2 (ja) * | 2013-07-15 | 2019-01-30 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | 新規5−置換ベンゾイミダゾリウム化合物 |
| WO2015121210A1 (en) * | 2014-02-11 | 2015-08-20 | Bayer Pharma Aktiengesellschaft | Benzimidazol-2-amines as midh1 inhibitors |
| CN106414429B (zh) * | 2014-06-03 | 2020-01-03 | 爱杜西亚药品有限公司 | 吡唑化合物及其作为t型钙通道阻断剂的用途 |
| EP3245202B1 (en) | 2015-01-12 | 2020-03-11 | Boehringer Ingelheim International GmbH | Tetrasubstituted benzimidazolium compounds useful in the treatment of respiratory diseases |
| CN107922353A (zh) * | 2015-06-26 | 2018-04-17 | 百时美施贵宝公司 | Ido抑制剂 |
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| EP3414224A1 (en) | 2018-12-19 |
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| KR102486298B1 (ko) | 2023-01-06 |
| EP3414224B1 (en) | 2022-03-23 |
| EP3414224A4 (en) | 2019-09-25 |
| JP2019510810A (ja) | 2019-04-18 |
| US20220054486A1 (en) | 2022-02-24 |
| RU2018128334A (ru) | 2020-03-10 |
| CN109071423A (zh) | 2018-12-21 |
| US11969425B2 (en) | 2024-04-30 |
| US20200046697A1 (en) | 2020-02-13 |
| JP6979036B2 (ja) | 2021-12-08 |
| CN113896685A (zh) | 2022-01-07 |
| WO2017139414A1 (en) | 2017-08-17 |
| MX2018009633A (es) | 2018-12-17 |
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