AU2014235280B2 - Histone demethylase inhibitors - Google Patents
Histone demethylase inhibitors Download PDFInfo
- Publication number
- AU2014235280B2 AU2014235280B2 AU2014235280A AU2014235280A AU2014235280B2 AU 2014235280 B2 AU2014235280 B2 AU 2014235280B2 AU 2014235280 A AU2014235280 A AU 2014235280A AU 2014235280 A AU2014235280 A AU 2014235280A AU 2014235280 B2 AU2014235280 B2 AU 2014235280B2
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- Prior art keywords
- pyrimidin
- compound
- alkyl
- found
- calc
- 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.)
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- 108010074870 Histone Demethylases Proteins 0.000 title claims abstract description 31
- 102000008157 Histone Demethylases Human genes 0.000 title claims abstract description 31
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 394
- 238000000034 method Methods 0.000 claims abstract description 207
- -1 pyrido[3,4-d]pyrimidin-4-one derivative compounds Chemical class 0.000 claims abstract description 123
- 239000000203 mixture Substances 0.000 claims abstract description 82
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 27
- 201000011510 cancer Diseases 0.000 claims abstract description 19
- 230000005764 inhibitory process Effects 0.000 claims abstract description 14
- 239000008194 pharmaceutical composition Chemical class 0.000 claims abstract description 11
- 238000011282 treatment Methods 0.000 claims abstract description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 97
- 125000000623 heterocyclic group Chemical group 0.000 claims description 64
- 125000002947 alkylene group Chemical group 0.000 claims description 63
- 125000001072 heteroaryl group Chemical group 0.000 claims description 59
- 150000003839 salts Chemical class 0.000 claims description 50
- 125000003118 aryl group Chemical group 0.000 claims description 47
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 46
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 29
- 125000005884 carbocyclylalkyl group Chemical group 0.000 claims description 25
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 239000001257 hydrogen Substances 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- 101001088892 Homo sapiens Lysine-specific demethylase 5A Proteins 0.000 claims description 15
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 15
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 230000002401 inhibitory effect Effects 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
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- 125000001769 aryl amino group Chemical group 0.000 claims description 7
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- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 6
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- 239000003814 drug Substances 0.000 claims description 5
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- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
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- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 3
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 3
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- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- 229910006074 SO2NH2 Inorganic materials 0.000 claims 2
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- 201000005112 urinary bladder cancer Diseases 0.000 abstract description 5
- 206010060862 Prostate cancer Diseases 0.000 abstract description 4
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- 230000001613 neoplastic effect Effects 0.000 abstract description 3
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- 239000000243 solution Substances 0.000 description 64
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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 48
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- ISIJQEHRDSCQIU-UHFFFAOYSA-N tert-butyl 2,7-diazaspiro[4.5]decane-7-carboxylate Chemical compound C1N(C(=O)OC(C)(C)C)CCCC11CNCC1 ISIJQEHRDSCQIU-UHFFFAOYSA-N 0.000 description 1
- XXZXGTFOJBGUFE-INIZCTEOSA-N tert-butyl 4-[(3s)-3-[4-(4-oxo-1h-pyrido[3,4-d]pyrimidin-2-yl)-1h-pyrazol-5-yl]pyrrolidine-1-carbonyl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1C(=O)N1C[C@@H](C2=C(C=NN2)C=2NC3=CN=CC=C3C(=O)N=2)CC1 XXZXGTFOJBGUFE-INIZCTEOSA-N 0.000 description 1
- QSQWENQPOSRWLP-UHFFFAOYSA-N tert-butyl 4-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]piperidine-1-carboxylate Chemical compound C1CN(C(=O)OC(C)(C)C)CCC1N1N=CC(B2OC(C)(C)C(C)(C)O2)=C1 QSQWENQPOSRWLP-UHFFFAOYSA-N 0.000 description 1
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Classifications
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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
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
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- Engineering & Computer Science (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Enzymes And Modification Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Immobilizing And Processing Of Enzymes And Microorganisms (AREA)
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| KR20170040805A (ko) | 2014-08-27 | 2017-04-13 | 길리애드 사이언시즈, 인코포레이티드 | 히스톤 데메틸라제를 억제하기 위한 화합물 및 방법 |
| US10030017B2 (en) | 2014-09-17 | 2018-07-24 | Celgene Quanticel Research, Inc. | Histone demethylase inhibitors |
| KR20170048591A (ko) | 2014-09-17 | 2017-05-08 | 셀젠 콴티셀 리서치, 인크. | 히스톤 데메틸라제 억제제 |
| CN107001358A (zh) | 2014-10-29 | 2017-08-01 | 东亚St株式会社 | 调节组蛋白赖氨酸脱甲基酶(kdm)催化活性的新型吡啶并嘧啶酮化合物 |
| CN107406414B (zh) * | 2015-01-09 | 2022-04-19 | 基因泰克公司 | 作为用于治疗癌症的组蛋白脱甲基酶kdm2b的抑制剂的(哌啶-3-基)(萘-2-基)甲酮衍生物 |
| WO2016112251A1 (en) * | 2015-01-09 | 2016-07-14 | Genentech, Inc. | 4,5-dihydroimidazole derivatives and their use as histone demethylase (kdm2b) inhibitors |
| US20170057955A1 (en) * | 2015-08-26 | 2017-03-02 | Dong-A Socio Holdings Co., Ltd. | Pyridopyrimidinone Compounds for Modulating the Catalytic Activity of Histone Lysine Demethylases (KDMs) |
| ES2921009T3 (es) * | 2016-03-15 | 2022-08-16 | Celgene Quanticel Res Inc | Inhibidores de desmetilasas de histonas |
| US10150754B2 (en) | 2016-04-19 | 2018-12-11 | Celgene Quanticel Research, Inc. | Histone demethylase inhibitors |
| KR102202984B1 (ko) | 2016-05-27 | 2021-01-13 | 길리애드 사이언시즈, 인코포레이티드 | Ns5a, ns5b 또는 ns3 억제제를 사용하여 b형 간염 바이러스 감염을 치료하는 방법 |
| BR102017010009A2 (pt) | 2016-05-27 | 2017-12-12 | Gilead Sciences, Inc. | Compounds for the treatment of hepatitis b virus infection |
| JOP20190024A1 (ar) | 2016-08-26 | 2019-02-19 | Gilead Sciences Inc | مركبات بيروليزين بها استبدال واستخداماتها |
| US10640499B2 (en) | 2016-09-02 | 2020-05-05 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| US10370342B2 (en) | 2016-09-02 | 2019-08-06 | Gilead Sciences, Inc. | Toll like receptor modulator compounds |
| CN117402852A (zh) | 2016-10-14 | 2024-01-16 | 精密生物科学公司 | 对乙肝病毒基因组中的识别序列特异性的工程化大范围核酸酶 |
| TWI784370B (zh) | 2017-01-31 | 2022-11-21 | 美商基利科學股份有限公司 | 替諾福韋埃拉酚胺(tenofovir alafenamide)之晶型 |
| JOP20180008A1 (ar) | 2017-02-02 | 2019-01-30 | Gilead Sciences Inc | مركبات لعلاج إصابة بعدوى فيروس الالتهاب الكبدي b |
| US11040947B2 (en) * | 2017-03-22 | 2021-06-22 | The Research Foundation For The State University Of New York | Substituted quinazolines as matrix metalloproteinase-9 hemopexin domain inhibitors |
| JOP20180040A1 (ar) | 2017-04-20 | 2019-01-30 | Gilead Sciences Inc | مثبطات pd-1/pd-l1 |
| CN111511754B (zh) | 2017-12-20 | 2023-09-12 | 捷克共和国有机化学与生物化学研究所 | 活化sting转接蛋白的具有膦酸酯键的2’3’环状二核苷酸 |
| AU2018392213B2 (en) | 2017-12-20 | 2021-03-04 | Institute Of Organic Chemistry And Biochemistry Ascr, V.V.I. | 3'3' cyclic dinucleotides with phosphonate bond activating the STING adaptor protein |
| UA126458C2 (uk) | 2018-02-13 | 2022-10-05 | Гіліад Сайєнсіз, Інк. | Інгібітори pd-1/pd-l1 |
| ES2962605T3 (es) | 2018-02-26 | 2024-03-20 | Gilead Sciences Inc | Compuestos de pirrolizina sustituidos como inhibidores de la replicación del VHB |
| WO2019195181A1 (en) | 2018-04-05 | 2019-10-10 | Gilead Sciences, Inc. | Antibodies and fragments thereof that bind hepatitis b virus protein x |
| TW202005654A (zh) | 2018-04-06 | 2020-02-01 | 捷克科學院有機化學與生物化學研究所 | ２，２，─環二核苷酸 |
| TWI818007B (zh) | 2018-04-06 | 2023-10-11 | 捷克科學院有機化學與生物化學研究所 | 2'3'-環二核苷酸 |
| TWI833744B (zh) | 2018-04-06 | 2024-03-01 | 捷克科學院有機化學與生物化學研究所 | 3'3'-環二核苷酸 |
| US11142750B2 (en) | 2018-04-12 | 2021-10-12 | Precision Biosciences, Inc. | Optimized engineered meganucleases having specificity for a recognition sequence in the Hepatitis B virus genome |
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| TW202014193A (zh) | 2018-05-03 | 2020-04-16 | 捷克科學院有機化學與生物化學研究所 | 包含碳環核苷酸之2’3’－環二核苷酸 |
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| KR20170048591A (ko) | 2014-09-17 | 2017-05-08 | 셀젠 콴티셀 리서치, 인크. | 히스톤 데메틸라제 억제제 |
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| WO2012052390A1 (en) * | 2010-10-19 | 2012-04-26 | Glaxo Group Limited | N-2-(2-pyridinyl)-4-pyrimidinyl-beta-alanine derivatives as inhibitors of histone demethylase jmjd3 |
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| CY1119476T1 (el) | 2018-03-07 |
| RS56561B1 (sr) | 2018-02-28 |
| PL2970211T3 (pl) | 2018-01-31 |
| WO2014151106A1 (en) | 2014-09-25 |
| EP2970211B1 (en) | 2017-07-26 |
| AU2014235280A1 (en) | 2015-09-17 |
| PT2970211T (pt) | 2017-10-31 |
| US9994562B2 (en) | 2018-06-12 |
| EP2970211A1 (en) | 2016-01-20 |
| EP2970211A4 (en) | 2016-08-03 |
| SMT201700493T1 (it) | 2017-11-15 |
| US20160039808A1 (en) | 2016-02-11 |
| LT2970211T (lt) | 2017-10-25 |
| SI2970211T1 (sl) | 2017-12-29 |
| US10526327B2 (en) | 2020-01-07 |
| JP6332654B2 (ja) | 2018-05-30 |
| JP2016512834A (ja) | 2016-05-09 |
| DK2970211T3 (en) | 2017-10-16 |
| US20180319793A1 (en) | 2018-11-08 |
| ES2644828T3 (es) | 2017-11-30 |
| HRP20171609T1 (hr) | 2017-12-15 |
| CA2903465A1 (en) | 2014-09-25 |
| HUE034906T2 (hu) | 2018-03-28 |
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