ES2960034T3 - Inhibidores de la arginasa y métodos de uso de los mismos - Google Patents
Inhibidores de la arginasa y métodos de uso de los mismos Download PDFInfo
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- ES2960034T3 ES2960034T3 ES20709706T ES20709706T ES2960034T3 ES 2960034 T3 ES2960034 T3 ES 2960034T3 ES 20709706 T ES20709706 T ES 20709706T ES 20709706 T ES20709706 T ES 20709706T ES 2960034 T3 ES2960034 T3 ES 2960034T3
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- Prior art keywords
- tert
- butyl
- mmol
- piperidine
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- 108700024123 Arginases Proteins 0.000 title abstract description 19
- 238000000034 method Methods 0.000 title abstract description 11
- 239000003112 inhibitor Substances 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 102
- 150000003839 salts Chemical class 0.000 claims abstract description 80
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 33
- 201000011510 cancer Diseases 0.000 claims abstract description 27
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 14
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 11
- 230000000241 respiratory effect Effects 0.000 claims abstract description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 9
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
- 239000003937 drug carrier Substances 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 150
- 239000000543 intermediate Substances 0.000 description 130
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 111
- 239000000243 solution Substances 0.000 description 81
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 74
- 235000019439 ethyl acetate Nutrition 0.000 description 74
- 239000000203 mixture Substances 0.000 description 64
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- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 33
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 31
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- 239000001257 hydrogen Substances 0.000 description 25
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
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- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 23
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 20
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- 101710129000 Arginase-1 Proteins 0.000 description 13
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- 239000005909 Kieselgur Substances 0.000 description 13
- 239000012298 atmosphere Substances 0.000 description 13
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 12
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- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- OCMOOIVZVZCUCQ-RBISFHTESA-N 2-O-benzyl 1-O-tert-butyl (2R,4S)-4-amino-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)butyl]piperidine-1,2-dicarboxylate Chemical compound N[C@@H]1C[C@@](N(CC1)C(=O)OC(C)(C)C)(C(=O)OCC1=CC=CC=C1)CCCCB1OC(C(O1)(C)C)(C)C OCMOOIVZVZCUCQ-RBISFHTESA-N 0.000 description 7
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 7
- GPDHNZNLPKYHCN-DZOOLQPHSA-N [[(z)-(1-cyano-2-ethoxy-2-oxoethylidene)amino]oxy-morpholin-4-ylmethylidene]-dimethylazanium;hexafluorophosphate Chemical compound F[P-](F)(F)(F)(F)F.CCOC(=O)C(\C#N)=N/OC(=[N+](C)C)N1CCOCC1 GPDHNZNLPKYHCN-DZOOLQPHSA-N 0.000 description 7
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- 230000002401 inhibitory effect Effects 0.000 description 7
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- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
- 239000004475 Arginine Substances 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
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- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
- C07F5/02—Boron compounds
- C07F5/025—Boronic and borinic acid compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/69—Boron compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
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| US201962802765P | 2019-02-08 | 2019-02-08 | |
| PCT/IB2020/050982 WO2020161675A1 (en) | 2019-02-08 | 2020-02-07 | Arginase inhibitors and methods of use thereof |
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| ES2960034T3 true ES2960034T3 (es) | 2024-02-29 |
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| ES20709706T Active ES2960034T3 (es) | 2019-02-08 | 2020-02-07 | Inhibidores de la arginasa y métodos de uso de los mismos |
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| CN117186134A (zh) * | 2018-02-17 | 2023-12-08 | 阿斯利康(瑞典)有限公司 | 精氨酸酶抑制剂及其使用方法 |
| TW202228720A (zh) | 2020-12-22 | 2022-08-01 | 波蘭商昂科艾倫迪治療法股份公司 | 精胺酸酶抑制劑及其使用方法 |
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| SE9901572D0 (sv) | 1999-05-03 | 1999-05-03 | Astra Ab | New compounds |
| SE0300907D0 (sv) | 2003-03-31 | 2003-03-31 | Astrazeneca Ab | Novel compounds |
| LT2389352T (lt) | 2009-01-26 | 2019-06-10 | The Trustees Of The University Of Pennsylvania | Arginazės inhibitoriai ir naudojimo būdai |
| SG10201503168VA (en) * | 2010-04-22 | 2015-06-29 | Mars Inc | Inhibitors of arginase and their therapeutic applications |
| HRP20160305T1 (hr) | 2010-10-26 | 2016-07-01 | Mars, Incorporated | Borati kao inhibitori arginaze |
| WO2013059437A1 (en) | 2011-10-19 | 2013-04-25 | Mars, Incorporated | Inhibitors of arginase and their therapeutic applications |
| RU2018138195A (ru) * | 2012-12-17 | 2018-12-18 | Пэрион Сайенсиз, Инк. | Соединения 3,5-диамино-6-хлор-n-(n-(4- фенилбутил)карбамимидоил)пиразин-2-карбоксамида |
| PL410665A1 (pl) | 2014-12-29 | 2016-07-04 | Oncoarendi Therapeutics Spółka Z Ograniczoną Odpowiedzialnością | Inhibitory arginazy oraz ich zastosowania terapeutyczne |
| US10143699B2 (en) * | 2015-06-23 | 2018-12-04 | Calithera Biosciences, Inc. | Compositions and methods for inhibiting arginase activity |
| WO2017175185A1 (en) | 2016-04-08 | 2017-10-12 | Novartis Ag | Heteroaryl butanoic acid derivatives as lta4h inhibitors |
| CN114989205A (zh) | 2016-12-22 | 2022-09-02 | 卡里塞拉生物科学股份公司 | 用于抑制精氨酸酶活性的组合物和方法 |
| CN108794517B (zh) | 2017-04-27 | 2021-03-30 | 南京谷睿生物科技有限公司 | 一种精氨酸酶抑制剂及其制备方法与用途 |
| CN117186134A (zh) * | 2018-02-17 | 2023-12-08 | 阿斯利康(瑞典)有限公司 | 精氨酸酶抑制剂及其使用方法 |
| EP3765006A4 (en) * | 2018-03-13 | 2022-02-23 | Merck Sharp & Dohme Corp. | ARGINASE INHIBITORS AND METHODS OF USE |
| CN111770756B (zh) | 2018-04-27 | 2023-03-31 | 四川科伦博泰生物医药股份有限公司 | 非天然氨基酸类衍生物、包含其的药物组合物及其制备方法和用途 |
| MA53427B1 (fr) * | 2018-08-22 | 2024-06-28 | Astrazeneca Ab | Inhibiteurs de l'arginase et leurs méthodes d'utilisation |
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2020
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