CA3033239A1 - Inhibiteurs spiro bicycliques de l'interaction menine-mll - Google Patents
Inhibiteurs spiro bicycliques de l'interaction menine-mll Download PDFInfo
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- CA3033239A1 CA3033239A1 CA3033239A CA3033239A CA3033239A1 CA 3033239 A1 CA3033239 A1 CA 3033239A1 CA 3033239 A CA3033239 A CA 3033239A CA 3033239 A CA3033239 A CA 3033239A CA 3033239 A1 CA3033239 A1 CA 3033239A1
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- optionally substituted
- 4alkyl
- hydrogen
- compound
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- 239000003112 inhibitor Substances 0.000 title abstract description 9
- 230000003993 interaction Effects 0.000 title description 18
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- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 8
- 125000001424 substituent group Chemical group 0.000 claims description 162
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- 239000001257 hydrogen Substances 0.000 claims description 152
- 125000001153 fluoro group Chemical group F* 0.000 claims description 114
- 150000003839 salts Chemical class 0.000 claims description 113
- 238000000034 method Methods 0.000 claims description 109
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 105
- 229910052757 nitrogen Inorganic materials 0.000 claims description 92
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- -1 -OC1-4alkyl Chemical group 0.000 claims description 76
- 229920006395 saturated elastomer Polymers 0.000 claims description 73
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 54
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 53
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 53
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- 229910052799 carbon Inorganic materials 0.000 claims description 51
- 229910052760 oxygen Inorganic materials 0.000 claims description 51
- 239000001301 oxygen Chemical group 0.000 claims description 51
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 50
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical group O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 48
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- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
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- 125000002098 pyridazinyl group Chemical group 0.000 claims description 21
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- 125000003226 pyrazolyl group Chemical group 0.000 claims description 20
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- 125000000168 pyrrolyl group Chemical group 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000004857 imidazopyridinyl group Chemical group N1C(=NC2=C1C=CC=N2)* 0.000 claims description 18
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- 150000002431 hydrogen Chemical class 0.000 claims description 8
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- 125000002541 furyl group Chemical group 0.000 claims description 7
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- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 5
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- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 206010009944 Colon cancer Diseases 0.000 claims description 4
- 208000006404 Large Granular Lymphocytic Leukemia Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 201000008717 T-cell large granular lymphocyte leukemia Diseases 0.000 claims description 4
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
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- 208000029742 colonic neoplasm Diseases 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 208000005017 glioblastoma Diseases 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 claims description 4
- 125000001977 isobenzofuranyl group Chemical group C=1(OC=C2C=CC=CC12)* 0.000 claims description 4
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 claims description 4
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
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- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical group F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 3
- 101150033506 HOX gene Proteins 0.000 claims description 3
- 108010081348 HRT1 protein Hairy Chemical group 0.000 claims description 3
- 102100021881 Hairy/enhancer-of-split related with YRPW motif protein 1 Human genes 0.000 claims description 3
- 101150029107 MEIS1 gene Proteins 0.000 claims description 3
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical group F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 68
- 101100237041 Homo sapiens MEIS1 gene Proteins 0.000 claims 2
- 102100022103 Histone-lysine N-methyltransferase 2A Human genes 0.000 abstract description 50
- 101001045846 Homo sapiens Histone-lysine N-methyltransferase 2A Proteins 0.000 abstract description 50
- 101710169972 Menin Proteins 0.000 abstract description 31
- 102100030550 Menin Human genes 0.000 abstract description 31
- 201000010099 disease Diseases 0.000 abstract description 19
- 241000124008 Mammalia Species 0.000 abstract description 6
- 239000008177 pharmaceutical agent Substances 0.000 abstract description 5
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- 208000011580 syndromic disease Diseases 0.000 abstract description 2
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- 239000000543 intermediate Substances 0.000 description 449
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 355
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 162
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 148
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 128
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- 239000000243 solution Substances 0.000 description 124
- 238000002360 preparation method Methods 0.000 description 123
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 113
- 239000011541 reaction mixture Substances 0.000 description 94
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 92
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- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 82
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- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 58
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- KRFZYPWUCOYOML-UHFFFAOYSA-N tert-butyl 3-acetylazetidine-1-carboxylate Chemical compound CC(=O)C1CN(C(=O)OC(C)(C)C)C1 KRFZYPWUCOYOML-UHFFFAOYSA-N 0.000 description 1
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- HNVBBNZWMSTMAZ-UHFFFAOYSA-N tert-butyl 4-acetylpiperidine-1-carboxylate Chemical compound CC(=O)C1CCN(C(=O)OC(C)(C)C)CC1 HNVBBNZWMSTMAZ-UHFFFAOYSA-N 0.000 description 1
- JYUQEWCJWDGCRX-UHFFFAOYSA-N tert-butyl 4-formylpiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(C=O)CC1 JYUQEWCJWDGCRX-UHFFFAOYSA-N 0.000 description 1
- IOKGWQZQCNXXLD-UHFFFAOYSA-N tert-butyl n-(3-bromopropyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCCBr IOKGWQZQCNXXLD-UHFFFAOYSA-N 0.000 description 1
- 150000003510 tertiary aliphatic amines Chemical class 0.000 description 1
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- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical class C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
La présente invention concerne des agents pharmaceutiques utiles pour la thérapie et/ou la prophylaxie chez un mammifère, et en particulier des composés spiro bicycliques, une composition pharmaceutique comprenant de tels composés, et leur utilisation en tant qu'inhibiteurs d'interactions ménine/protéine MLL/protéine, utiles pour le traitement de maladies telles que le cancer, le syndrome myélodysplasique (MDS) et le diabète.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662394295P | 2016-09-14 | 2016-09-14 | |
| US62/394,295 | 2016-09-14 | ||
| EP16192431 | 2016-10-05 | ||
| EP16192431.1 | 2016-10-05 | ||
| PCT/EP2017/073004 WO2018050686A1 (fr) | 2016-09-14 | 2017-09-13 | Inhibiteurs spiro bicycliques de l'interaction ménine-mll |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA3033239A1 true CA3033239A1 (fr) | 2018-03-22 |
Family
ID=57083210
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA3033239A Pending CA3033239A1 (fr) | 2016-09-14 | 2017-09-13 | Inhibiteurs spiro bicycliques de l'interaction menine-mll |
Country Status (4)
| Country | Link |
|---|---|
| CA (1) | CA3033239A1 (fr) |
| EA (1) | EA201990699A1 (fr) |
| TW (1) | TWI738864B (fr) |
| WO (1) | WO2018050686A1 (fr) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112771055A (zh) * | 2018-08-08 | 2021-05-07 | 大日本住友制药株式会社 | 光学活性桥接哌啶衍生物 |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10246464B2 (en) | 2014-09-09 | 2019-04-02 | The Regents Of The University Of Michigan | Thienopyrimidine and thienopyridine compounds and methods of use thereof |
| TWI703150B (zh) | 2015-06-04 | 2020-09-01 | 美商庫拉腫瘤技術股份有限公司 | 用於抑制ｍｅｎｉｎ及ｍｌｌ蛋白之交互作用的方法及組合物 |
| US10588907B2 (en) | 2015-06-04 | 2020-03-17 | Kura Oncology, Inc. | Methods and compositions for inhibiting the interaction of menin with MLL proteins |
| FI3429591T3 (fi) | 2016-03-16 | 2023-06-15 | Kura Oncology Inc | Substituoituja tieno[2,3-d]pyrimidiinijohdannaisia meniini-mll:n estäjinä ja käyttömenetelmiä |
| EP3429585B1 (fr) | 2016-03-16 | 2021-11-24 | Kura Oncology, Inc. | Inhibiteurs bicycliques pontés de ménine-mll et méthodes d'utilisation |
| SI3512857T1 (sl) | 2016-09-14 | 2021-07-30 | Janssen Pharmaceutica Nv | Spiro biciklični zaviralci interakcije menin-MLL |
| WO2018050684A1 (fr) | 2016-09-14 | 2018-03-22 | Janssen Pharmaceutica Nv | Inhibiteurs bicycliques fusionnés de l'interaction ménine-mll |
| US12084462B2 (en) | 2016-09-14 | 2024-09-10 | Janssen Pharmaceutica Nv | Spiro bicyclic inhibitors of menin-MLL interaction |
| JP7142010B2 (ja) | 2016-12-15 | 2022-09-26 | ヤンセン ファーマシューティカ エヌ．ベー． | メニン－ｍｌｌ相互作用のアゼパン阻害剤 |
| WO2018175746A1 (fr) | 2017-03-24 | 2018-09-27 | Kura Oncology, Inc. | Méthodes de traitement d'hémopathies malignes et du sarcome d'ewing |
| US11542248B2 (en) | 2017-06-08 | 2023-01-03 | Kura Oncology, Inc. | Methods and compositions for inhibiting the interaction of menin with MLL proteins |
| WO2019060365A1 (fr) | 2017-09-20 | 2019-03-28 | Kura Oncology, Inc. | Inhibiteurs substitués de ménine-mll et méthodes d'utilisation |
| CN111601807B (zh) * | 2017-12-20 | 2023-03-31 | 詹森药业有限公司 | Menin-mll相互作用的外型-氮杂螺抑制剂 |
| US11396517B1 (en) | 2017-12-20 | 2022-07-26 | Janssen Pharmaceutica Nv | Exo-aza spiro inhibitors of menin-MLL interaction |
| US11325921B2 (en) | 2018-03-30 | 2022-05-10 | Sumitomo Dainippon Pharma Co., Ltd. | Optically active crosslinked cyclic secondary amine derivative |
| TWI815954B (zh) | 2018-08-27 | 2023-09-21 | 日商住友製藥股份有限公司 | 光學活性氮雜雙環衍生物 |
| US10815241B2 (en) | 2018-08-27 | 2020-10-27 | Sumitomo Dainippon Pharma Co., Ltd. | Optically active azabicyclo ring derivative |
| MX2021006696A (es) | 2018-12-06 | 2021-07-07 | Daiichi Sankyo Co Ltd | Derivado de cicloalcano-1,3-diamina. |
| US20220380365A1 (en) * | 2019-09-27 | 2022-12-01 | Sumitomo Dainippon Pharma Co., Ltd. | Crosslinked optically active secondary amine derivative |
| MX2022007652A (es) | 2019-12-19 | 2022-09-23 | Janssen Pharmaceutica Nv | Derivados espiráncos sustituidos de cadena lineal. |
| BR112023023154A2 (pt) | 2021-05-08 | 2024-01-23 | Janssen Pharmaceutica Nv | Derivados espiro substituídos |
| AU2022275192A1 (en) | 2021-05-08 | 2024-01-04 | Janssen Pharmaceutica Nv | Substituted spiro derivatives |
| AU2022286467A1 (en) | 2021-06-01 | 2024-01-25 | Janssen Pharmaceutica Nv | SUBSTITUTED PHENYL-1H-PYRROLO[2, 3-c]PYRIDINE DERIVATIVES |
| US20250333421A1 (en) | 2021-06-03 | 2025-10-30 | Janssen Pharmaceutica Nv | Pyridazines or 1,2,4-triazines substituted by spirocyclic amines |
| CA3220099A1 (fr) | 2021-06-17 | 2022-12-22 | Wei Cai | Sel de besylate (r)-n-ethyl-5-fluoro-n-isopropyl-2-((5-(2-(6-((2-methoxyethyl)(methyl)amino)-2-m ethylhexan-3-yl)-2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl)oxy)benzamide pour le traitement de maladies telles que le cance |
| CA3261797A1 (fr) * | 2022-08-11 | 2024-02-15 | Remynd N V | Dérivés d'(aza)spiroheptane pour le traitement de troubles neurodégénératifs |
| KR20250109775A (ko) | 2022-11-24 | 2025-07-17 | 오리존 지노믹스 에스.에이. | 암 치료를 위한 lsd1 억제제 및 메닌 억제제의 조합 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2473054B1 (fr) | 2009-09-04 | 2017-06-14 | The Regents of the University of Michigan | Compositions et méthodes de traitement de la leucémie |
| AU2014249233A1 (en) | 2013-03-13 | 2015-09-24 | The Regents Of The University Of Michigan | Compositions comprising thienopyrimidine and thienopyridine compounds and methods of use thereof |
| CN105732636B (zh) * | 2014-12-30 | 2020-04-21 | 广东东阳光药业有限公司 | 杂芳化合物及其在药物中的应用 |
| WO2017112768A1 (fr) | 2015-12-22 | 2017-06-29 | Vitae Pharmaceuticals, Inc. | Inhibiteurs de l'interaction ménine-mll |
-
2017
- 2017-09-13 CA CA3033239A patent/CA3033239A1/fr active Pending
- 2017-09-13 TW TW106131467A patent/TWI738864B/zh not_active IP Right Cessation
- 2017-09-13 EA EA201990699A patent/EA201990699A1/ru unknown
- 2017-09-13 WO PCT/EP2017/073004 patent/WO2018050686A1/fr not_active Ceased
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112771055A (zh) * | 2018-08-08 | 2021-05-07 | 大日本住友制药株式会社 | 光学活性桥接哌啶衍生物 |
| CN112771055B (zh) * | 2018-08-08 | 2023-10-20 | 住友制药株式会社 | 光学活性桥接哌啶衍生物 |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201823250A (zh) | 2018-07-01 |
| TWI738864B (zh) | 2021-09-11 |
| WO2018050686A1 (fr) | 2018-03-22 |
| EA201990699A1 (ru) | 2019-09-30 |
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