CA2974788C - A 2-pyrimidinyl substituted pyridinyl heterocyclic compound and a pharmaceutical composition comprising the same - Google Patents
A 2-pyrimidinyl substituted pyridinyl heterocyclic compound and a pharmaceutical composition comprising the same Download PDFInfo
- Publication number
- CA2974788C CA2974788C CA2974788A CA2974788A CA2974788C CA 2974788 C CA2974788 C CA 2974788C CA 2974788 A CA2974788 A CA 2974788A CA 2974788 A CA2974788 A CA 2974788A CA 2974788 C CA2974788 C CA 2974788C
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- Canada
- Prior art keywords
- amino
- fluoro
- bipyridin
- pyrimidin
- compound
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- -1 pyridinyl heterocyclic compound Chemical class 0.000 title claims abstract description 43
- 239000008194 pharmaceutical composition Chemical class 0.000 title claims abstract description 23
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 508
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 65
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 54
- 150000003839 salts Chemical class 0.000 claims abstract description 48
- LJXQPZWIHJMPQQ-UHFFFAOYSA-N pyrimidin-2-amine Chemical group NC1=NC=CC=N1 LJXQPZWIHJMPQQ-UHFFFAOYSA-N 0.000 claims abstract description 37
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Chemical group COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims abstract description 29
- 102000003903 Cyclin-dependent kinases Human genes 0.000 claims abstract description 25
- 108090000266 Cyclin-dependent kinases Proteins 0.000 claims abstract description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 25
- 208000014644 Brain disease Diseases 0.000 claims abstract description 20
- 230000003412 degenerative effect Effects 0.000 claims abstract description 20
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 16
- 229910052736 halogen Chemical group 0.000 claims abstract description 15
- 150000002367 halogens Chemical group 0.000 claims abstract description 15
- 125000001424 substituent group Chemical group 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 9
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical group C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 4
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 4
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- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 3
- GRFNBEZIAWKNCO-UHFFFAOYSA-N 3-pyridinol Chemical compound OC1=CC=CN=C1 GRFNBEZIAWKNCO-UHFFFAOYSA-N 0.000 claims description 89
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- 125000002971 oxazolyl group Chemical group 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 208000021310 pituitary gland adenoma Diseases 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- QLULGIRFKAWHOJ-UHFFFAOYSA-N pyridin-4-ylboronic acid Chemical compound OB(O)C1=CC=NC=C1 QLULGIRFKAWHOJ-UHFFFAOYSA-N 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 230000022983 regulation of cell cycle Effects 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229940071182 stannate Drugs 0.000 description 1
- 125000005402 stannate group Chemical group 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 239000006190 sub-lingual tablet Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000007761 synergistic anti-cancer Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 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
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005309 thioalkoxy group Chemical group 0.000 description 1
- 125000000341 threoninyl group Chemical group [H]OC([H])(C([H])([H])[H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- WLPUWLXVBWGYMZ-UHFFFAOYSA-N tricyclohexylphosphine Chemical compound C1CCCCC1P(C1CCCCC1)C1CCCCC1 WLPUWLXVBWGYMZ-UHFFFAOYSA-N 0.000 description 1
- IHIXIJGXTJIKRB-UHFFFAOYSA-N trisodium vanadate Chemical compound [Na+].[Na+].[Na+].[O-][V]([O-])([O-])=O IHIXIJGXTJIKRB-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- WKOLLVMJNQIZCI-UHFFFAOYSA-M vanillate Chemical compound COC1=CC(C([O-])=O)=CC=C1O WKOLLVMJNQIZCI-UHFFFAOYSA-M 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR20150017339 | 2015-02-04 | ||
| KR10-2015-0017339 | 2015-02-04 | ||
| PCT/KR2016/001133 WO2016126085A2 (ko) | 2015-02-04 | 2016-02-02 | 헤테로 고리 화합물 및 그를 포함하는 약제학적 조성물 |
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| CA2974788A1 CA2974788A1 (en) | 2016-08-11 |
| CA2974788C true CA2974788C (en) | 2023-04-11 |
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| CA2974788A Active CA2974788C (en) | 2015-02-04 | 2016-02-02 | A 2-pyrimidinyl substituted pyridinyl heterocyclic compound and a pharmaceutical composition comprising the same |
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| EP (1) | EP3255042B1 (enExample) |
| JP (1) | JP6615899B2 (enExample) |
| KR (1) | KR101783642B1 (enExample) |
| CN (1) | CN107250130B (enExample) |
| AU (1) | AU2016216253B2 (enExample) |
| BR (1) | BR112017016465B1 (enExample) |
| CA (1) | CA2974788C (enExample) |
| DK (1) | DK3255042T3 (enExample) |
| ES (1) | ES2854707T3 (enExample) |
| IL (1) | IL253538B (enExample) |
| RU (1) | RU2710743C2 (enExample) |
| SG (1) | SG11201705952SA (enExample) |
| WO (1) | WO2016126085A2 (enExample) |
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| US10513509B2 (en) | 2016-05-26 | 2019-12-24 | Recurium Ip Holdings, Llc | EGFR inhibitor compounds |
| EP3843741A4 (en) * | 2018-08-30 | 2022-11-30 | The Regents of the University of California | KINASE IRE1 INHIBITORS AND THEIR USES |
| BR112021015004A2 (pt) * | 2019-01-29 | 2021-10-05 | Beta Pharma, Inc. | Derivados de 2 h-indazol como agentes terapêuticos para cânceres cerebrais e metastases cerebrais |
| WO2021045584A1 (ko) * | 2019-09-06 | 2021-03-11 | 비욘드바이오주식회사 | 2'-아미노-6-(2-아미노-6-메틸피리미딘-4-일)-3'-플루오로-[2,4'-바이피리딘]-5-올 2염산염 및 이를 포함하는 약제학적 조성물 |
| WO2021045586A1 (ko) * | 2019-09-06 | 2021-03-11 | 비욘드바이오주식회사 | 2'-아미노-6-(2-아미노-6-(1-이소프로필피페리딘-4-일)-5-메틸피리미딘-4-일)-3'-플루오로-[2,4'-바이피리딘]-5-올 3염산염 및 이를 포함하는 약제학적 조성물 |
| KR102443873B1 (ko) * | 2019-09-06 | 2022-09-19 | 비욘드바이오주식회사 | 피리미딘일 바이피리딘 화합물의 제조방법 및 그를 위한 중간체 |
| KR20210029693A (ko) | 2019-09-06 | 2021-03-16 | 비욘드바이오주식회사 | 2,6-비스-(2-아미노피리미딘-4-일)피리딘-3-올 2염산염 및 이를 포함하는 약제학적 조성물 |
| MX2022005991A (es) * | 2019-11-18 | 2022-06-17 | Chugai Pharmaceutical Co Ltd | Farmaco combinado. |
| CN111558044B (zh) * | 2020-06-01 | 2022-02-11 | 中山大学肿瘤防治中心（中山大学附属肿瘤医院、中山大学肿瘤研究所） | 一种包含舒尼替尼的药物组合物及其制剂和应用 |
| CN116082310B (zh) * | 2023-02-17 | 2024-08-20 | 厦门大学 | 联吡啶酰胺类衍生物及其制备和应用 |
| CN116751195B (zh) * | 2023-06-21 | 2025-03-07 | 杭州科兴生物化工有限公司 | 联吡啶类化合物、其可药用的盐以及制备方法和应用 |
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| US6440965B1 (en) | 1997-10-15 | 2002-08-27 | Krenitsky Pharmaceuticals, Inc. | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system |
| GB0013655D0 (en) * | 2000-06-05 | 2000-07-26 | Prolifix Ltd | Therapeutic compounds |
| ES2320973T3 (es) * | 2000-06-12 | 2009-06-01 | EISAI R&D MANAGEMENT CO., LTD. | Compuestos de 1,2-dihidropiridina, procedimiento para su preparacion y uso de los mismos. |
| JP2004534779A (ja) * | 2001-05-30 | 2004-11-18 | エルジー ライフサイエンス リミテッド | 疾病治療用プロテインキナーゼ阻害剤 |
| GB0129260D0 (en) * | 2001-12-06 | 2002-01-23 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
| MXPA05001804A (es) * | 2002-08-14 | 2005-05-27 | Vertex Pharma | Inhibidores de proteinas cinasas y usos de los mismos. |
| CN1742723A (zh) | 2004-09-02 | 2006-03-08 | 天津倍方科技发展有限公司 | 含有替莫唑胺－8－羧酸酯的药物组合物以及该类化合物用于制备抗肿瘤药物的用途 |
| WO2008106202A1 (en) * | 2007-02-27 | 2008-09-04 | Housey Gerard M | Theramutein modulators |
| WO2010018458A2 (en) * | 2008-08-12 | 2010-02-18 | Crystalgenomics, Inc. | Phenol derivatives and methods of use thereof |
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Also Published As
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|---|---|
| BR112017016465A2 (pt) | 2018-06-19 |
| DK3255042T3 (da) | 2021-02-08 |
| CN107250130A (zh) | 2017-10-13 |
| AU2016216253B2 (en) | 2019-11-21 |
| WO2016126085A2 (ko) | 2016-08-11 |
| EP3255042A4 (en) | 2018-08-01 |
| US20190135786A1 (en) | 2019-05-09 |
| US10611754B2 (en) | 2020-04-07 |
| RU2017130825A3 (enExample) | 2019-08-12 |
| JP2018504449A (ja) | 2018-02-15 |
| SG11201705952SA (en) | 2017-09-28 |
| NZ734084A (en) | 2023-09-29 |
| US20180273510A1 (en) | 2018-09-27 |
| WO2016126085A3 (ko) | 2016-11-03 |
| CN107250130B (zh) | 2019-11-08 |
| KR101783642B1 (ko) | 2017-10-10 |
| BR112017016465B1 (pt) | 2023-11-14 |
| EP3255042B1 (en) | 2020-12-30 |
| RU2017130825A (ru) | 2019-03-04 |
| ES2854707T3 (es) | 2021-09-22 |
| JP6615899B2 (ja) | 2019-12-04 |
| EP3255042A2 (en) | 2017-12-13 |
| AU2016216253A1 (en) | 2017-08-17 |
| KR20160096033A (ko) | 2016-08-12 |
| US20200190062A1 (en) | 2020-06-18 |
| IL253538A0 (en) | 2017-09-28 |
| IL253538B (en) | 2020-09-30 |
| US10227328B2 (en) | 2019-03-12 |
| RU2710743C2 (ru) | 2020-01-10 |
| CA2974788A1 (en) | 2016-08-11 |
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