CN102260258B - 吡啶并[2,3-d]嘧啶衍生物,它们的制备,在治疗中的用途 - Google Patents
吡啶并[2,3-d]嘧啶衍生物,它们的制备,在治疗中的用途 Download PDFInfo
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- CN102260258B CN102260258B CN201110187994.9A CN201110187994A CN102260258B CN 102260258 B CN102260258 B CN 102260258B CN 201110187994 A CN201110187994 A CN 201110187994A CN 102260258 B CN102260258 B CN 102260258B
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- alkyl
- pyrido
- dichlorophenyl
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- 238000002360 preparation method Methods 0.000 title claims abstract description 47
- 159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 title abstract description 4
- 238000002560 therapeutic procedure Methods 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 141
- 238000011282 treatment Methods 0.000 claims abstract description 14
- -1 2,6-dichlorophenyl Chemical group 0.000 claims description 58
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 23
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
- 150000001412 amines Chemical class 0.000 claims description 22
- 150000003839 salts Chemical class 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 16
- 239000002253 acid Substances 0.000 claims description 13
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 12
- 229910052736 halogen Chemical group 0.000 claims description 12
- 150000002367 halogens Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 229910052794 bromium Inorganic materials 0.000 claims description 9
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- 239000008194 pharmaceutical composition Substances 0.000 claims description 8
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical group [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 8
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- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 6
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000003282 alkyl amino group Chemical group 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 230000004663 cell proliferation Effects 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000003943 azolyl group Chemical group 0.000 claims description 4
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 239000002798 polar solvent Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 3
- 125000002393 azetidinyl group Chemical group 0.000 claims description 3
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 125000002757 morpholinyl group Chemical group 0.000 claims description 3
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- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
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- 230000002062 proliferating effect Effects 0.000 abstract description 2
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 26
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- 239000002552 dosage form Substances 0.000 description 6
- 239000002243 precursor Substances 0.000 description 6
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
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- 150000004677 hydrates Chemical class 0.000 description 3
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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
- 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
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0507032A FR2887882B1 (fr) | 2005-07-01 | 2005-07-01 | Derives de pyrido[2,3-d] pyrimidine, leur preparation, leur application en therapeutique |
| FR0507032 | 2005-07-01 |
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|---|---|---|---|
| CN2006800237082A Division CN101213196B (zh) | 2005-07-01 | 2006-06-29 | 吡啶并[2,3-d]嘧啶衍生物，它们的制备，在治疗中的用途 |
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| Publication Number | Publication Date |
|---|---|
| CN102260258A CN102260258A (zh) | 2011-11-30 |
| CN102260258B true CN102260258B (zh) | 2015-01-07 |
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|---|---|---|---|
| CN201110187994.9A Expired - Fee Related CN102260258B (zh) | 2005-07-01 | 2006-06-29 | 吡啶并[2,3-d]嘧啶衍生物,它们的制备,在治疗中的用途 |
| CN2006800237082A Expired - Fee Related CN101213196B (zh) | 2005-07-01 | 2006-06-29 | 吡啶并[2,3-d]嘧啶衍生物，它们的制备，在治疗中的用途 |
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| Application Number | Title | Priority Date | Filing Date |
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| CN2006800237082A Expired - Fee Related CN101213196B (zh) | 2005-07-01 | 2006-06-29 | 吡啶并[2,3-d]嘧啶衍生物，它们的制备，在治疗中的用途 |
Country Status (40)
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2873118B1 (fr) | 2004-07-15 | 2007-11-23 | Sanofi Synthelabo | Derives de pyrido-pyrimidine, leur application en therapeutique |
| FR2887882B1 (fr) * | 2005-07-01 | 2007-09-07 | Sanofi Aventis Sa | Derives de pyrido[2,3-d] pyrimidine, leur preparation, leur application en therapeutique |
| FR2896246B1 (fr) | 2006-01-13 | 2008-08-15 | Sanofi Aventis Sa | Derives de pyrido-pyrimidone, leur preparation, leur application en therapeutique. |
| FR2910813B1 (fr) * | 2006-12-28 | 2009-02-06 | Sanofi Aventis Sa | Nouvelle utilisation therapeutique pour le traitement des leucemies |
| WO2010042998A1 (en) | 2008-10-17 | 2010-04-22 | Akaal Pharma Pty Ltd | S1p receptors modulators |
| WO2010043000A1 (en) | 2008-10-17 | 2010-04-22 | Akaal Pharma Pty Ltd | S1p receptors modulators and their use thereof |
| FR2948568B1 (fr) * | 2009-07-30 | 2012-08-24 | Sanofi Aventis | Formulation pharmaceutique |
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| CN103833771A (zh) * | 2012-11-22 | 2014-06-04 | 天津滨江药物研发有限公司 | 作为蛋白激酶Mek抑制剂的苯并五元杂环化合物及其制备方法和用途 |
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| CN1169726A (zh) * | 1994-11-14 | 1998-01-07 | 沃尼尔·朗伯公司 | 用于抑制蛋白质酪氨酸激酶介导的细胞增殖的6－芳基吡啶并[2,3－d]嘧啶和1,5－二氮杂 |
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