JP2000506847A - ４―アミノ―ピリミジン誘導体、これらの化合物を含む医薬品、それらの使用及び製造法 - Google Patents
４―アミノ―ピリミジン誘導体、これらの化合物を含む医薬品、それらの使用及び製造法Info
- Publication number
- JP2000506847A JP2000506847A JP9531444A JP53144497A JP2000506847A JP 2000506847 A JP2000506847 A JP 2000506847A JP 9531444 A JP9531444 A JP 9531444A JP 53144497 A JP53144497 A JP 53144497A JP 2000506847 A JP2000506847 A JP 2000506847A
- Authority
- JP
- Japan
- Prior art keywords
- group
- amino
- piperidinyl
- alkyl
- pyrimidine
- 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.)
- Pending
Links
- 150000005007 4-aminopyrimidines Chemical class 0.000 title claims abstract description 8
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 title claims description 51
- 239000003814 drug Substances 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 22
- -1 1-piperazinyl group Chemical group 0.000 claims description 170
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 92
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 23
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 22
- 239000000460 chlorine Substances 0.000 claims description 20
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 19
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- 229910052801 chlorine Inorganic materials 0.000 claims description 19
- 239000011737 fluorine Substances 0.000 claims description 19
- 229910052731 fluorine Inorganic materials 0.000 claims description 19
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 13
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 125000001841 imino group Chemical group [H]N=* 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 150000001721 carbon Chemical group 0.000 claims description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 7
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000004487 4-tetrahydropyranyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- QVCZZJBJZVMFCN-UHFFFAOYSA-N 7-(4-aminopiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrido[4,3-d]pyrimidin-4-amine Chemical compound C1CC(N)CCN1C1=CC2=NC=NC(NC=3C=C(Cl)C(F)=CC=3)=C2C=N1 QVCZZJBJZVMFCN-UHFFFAOYSA-N 0.000 claims description 5
- 125000003282 alkyl amino group Chemical group 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 5
- 125000006518 morpholino carbonyl group Chemical group [H]C1([H])OC([H])([H])C([H])([H])N(C(*)=O)C1([H])[H] 0.000 claims description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims description 5
- 125000006239 protecting group Chemical group 0.000 claims description 5
- FYZNVJXVYULLRI-UHFFFAOYSA-N 6-(4-aminopiperidin-1-yl)-n-(3-chloro-4-fluorophenyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1CC(N)CCN1C(N=CC1=NC=N2)=CC1=C2NC1=CC=C(F)C(Cl)=C1 FYZNVJXVYULLRI-UHFFFAOYSA-N 0.000 claims description 4
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 229910052740 iodine Inorganic materials 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 230000035755 proliferation Effects 0.000 claims description 4
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 3
- LPTMQSAZKAPFBB-UMSPYCQHSA-N NC1=C(C=C(C=C1Br)NC=1C2=C(N=CN=1)C=NC(=C2)N[C@@H]1CC[C@H](CC1)O)Br Chemical compound NC1=C(C=C(C=C1Br)NC=1C2=C(N=CN=1)C=NC(=C2)N[C@@H]1CC[C@H](CC1)O)Br LPTMQSAZKAPFBB-UMSPYCQHSA-N 0.000 claims description 3
- 230000002159 abnormal effect Effects 0.000 claims description 3
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 230000029936 alkylation Effects 0.000 claims description 3
- 238000005804 alkylation reaction Methods 0.000 claims description 3
- 230000009435 amidation Effects 0.000 claims description 3
- 238000007112 amidation reaction Methods 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 239000000969 carrier Substances 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 150000007522 mineralic acids Chemical class 0.000 claims description 3
- 150000007524 organic acids Chemical class 0.000 claims description 3
- 235000005985 organic acids Nutrition 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 3
- 238000005932 reductive alkylation reaction Methods 0.000 claims description 3
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 3
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- BBQBGOKSFHWOFY-UHFFFAOYSA-N ClC=1C=C(C=CC=1F)NC=1C2=C(N=CN=1)C=NC(=C2)NC1CN2CCC1CC2 Chemical compound ClC=1C=C(C=CC=1F)NC=1C2=C(N=CN=1)C=NC(=C2)NC1CN2CCC1CC2 BBQBGOKSFHWOFY-UHFFFAOYSA-N 0.000 claims description 2
- 206010027476 Metastases Diseases 0.000 claims description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 2
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 2
- 201000011510 cancer Diseases 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 2
- 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 2
- 125000004185 ester group Chemical group 0.000 claims description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
- 230000009401 metastasis Effects 0.000 claims description 2
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims 3
- DUCQQIHFCRFOCR-UHFFFAOYSA-N n-(3-bromophenyl)-6-piperidin-1-ylpyrido[3,4-d]pyrimidin-4-amine Chemical compound BrC1=CC=CC(NC=2C3=CC(=NC=C3N=CN=2)N2CCCCC2)=C1 DUCQQIHFCRFOCR-UHFFFAOYSA-N 0.000 claims 2
- 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 1
- 206010029113 Neovascularisation Diseases 0.000 claims 1
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 1
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims 1
- 125000005277 alkyl imino group Chemical group 0.000 claims 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 1
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims 1
- AGBGLYLKNYLQEL-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-[4-(1-methylpiperidin-4-yl)piperidin-1-yl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCC1C1CCN(C=2N=CC3=NC=NC(NC=4C=C(Cl)C(F)=CC=4)=C3C=2)CC1 AGBGLYLKNYLQEL-UHFFFAOYSA-N 0.000 claims 1
- UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 210000003556 vascular endothelial cell Anatomy 0.000 claims 1
- 239000002253 acid Substances 0.000 abstract description 10
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 abstract description 6
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 abstract description 6
- 201000010099 disease Diseases 0.000 abstract description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 6
- 150000007513 acids Chemical class 0.000 abstract description 4
- 230000002401 inhibitory effect Effects 0.000 abstract description 4
- 230000001404 mediated effect Effects 0.000 abstract description 3
- 230000001613 neoplastic effect Effects 0.000 abstract description 2
- 230000011664 signaling Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 66
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 239000000203 mixture Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- 239000004480 active ingredient Substances 0.000 description 19
- 238000002844 melting Methods 0.000 description 18
- 230000008018 melting Effects 0.000 description 18
- 210000004027 cell Anatomy 0.000 description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 239000003826 tablet Substances 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 13
- 235000011114 ammonium hydroxide Nutrition 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
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- 238000001819 mass spectrum Methods 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
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- 229920002261 Corn starch Polymers 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
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- WCDWBPCFGJXFJZ-UHFFFAOYSA-N etanidazole Chemical group OCCNC(=O)CN1C=CN=C1[N+]([O-])=O WCDWBPCFGJXFJZ-UHFFFAOYSA-N 0.000 description 6
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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- 239000007903 gelatin capsule Substances 0.000 description 3
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- BCIIMDOZSUCSEN-UHFFFAOYSA-N piperidin-4-amine Chemical compound NC1CCNCC1 BCIIMDOZSUCSEN-UHFFFAOYSA-N 0.000 description 1
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- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-M 0.000 description 1
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Classifications
-
- 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
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dermatology (AREA)
- Immunology (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 (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE1996108631 DE19608631A1 (de) | 1996-03-06 | 1996-03-06 | 4-Amino-pyrimidin-Derivate, diese Verbindungen enthaltende Arnzeimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19608631.0 | 1996-03-06 | ||
| DE19629652A DE19629652A1 (de) | 1996-03-06 | 1996-07-23 | 4-Amino-pyrimidin-Derivate, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
| DE19629652.8 | 1996-07-23 | ||
| PCT/EP1997/001057 WO1997032881A1 (de) | 1996-03-06 | 1997-03-03 | 4-amino-pyrimidin-derivate, diese verbindungen enthaltende arzneimittel, deren verwendung und verfahren zu ihrer herstellung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000506847A true JP2000506847A (ja) | 2000-06-06 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP9531444A Pending JP2000506847A (ja) | 1996-03-06 | 1997-03-03 | ４―アミノ―ピリミジン誘導体、これらの化合物を含む医薬品、それらの使用及び製造法 |
Country Status (19)
| Country | Link |
|---|---|
| EP (1) | EP0885226A1 (pt) |
| JP (1) | JP2000506847A (pt) |
| KR (1) | KR19990087550A (pt) |
| CN (1) | CN1212695A (pt) |
| AU (1) | AU710274B2 (pt) |
| BG (1) | BG102708A (pt) |
| BR (1) | BR9708312A (pt) |
| CA (1) | CA2243994A1 (pt) |
| CZ (1) | CZ281798A3 (pt) |
| DE (1) | DE19629652A1 (pt) |
| EE (1) | EE9800277A (pt) |
| HU (1) | HUP9901820A3 (pt) |
| IL (1) | IL125404A0 (pt) |
| NO (1) | NO984084D0 (pt) |
| NZ (1) | NZ331546A (pt) |
| PL (1) | PL328771A1 (pt) |
| SK (1) | SK120598A3 (pt) |
| TR (1) | TR199801749T2 (pt) |
| WO (1) | WO1997032881A1 (pt) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008530212A (ja) * | 2005-02-16 | 2008-08-07 | シェーリング コーポレイション | Ｃｘｃｒ３アンタゴニスト活性を有するピペラジン−ピペリジン |
| JP2012510481A (ja) * | 2008-12-01 | 2012-05-10 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌に対するオータキシン阻害剤としての２，５−ジアミノ−置換ピリド［４，３−ｄ］ピリミジン |
Families Citing this family (79)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0880508B1 (en) | 1996-02-13 | 2003-04-16 | AstraZeneca AB | Quinazoline derivatives as vegf inhibitors |
| IL125954A (en) | 1996-03-05 | 2003-06-24 | Zeneca Ltd | Quinazoline derivatives, processes for their preparation, pharmaceutical compositions containing them and use thereof in the manufacture of medicaments having an antiangiogenic and/or vascular permeability reducing effect |
| EP1396489A1 (en) * | 1999-01-27 | 2004-03-10 | Pfizer Products Inc. | Heteroaromatic bicyclic derivatives useful as anticancer agents |
| UA71945C2 (en) * | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| PT1244647E (pt) | 1999-11-05 | 2006-10-31 | Astrazeneca Ab | Derivados de quinazolina como inibidores de vegf |
| CA2530023A1 (en) | 2003-06-24 | 2004-12-29 | Neurosearch A/S | Novel 8-aza-bicyclo[3.2.1]octane derivatives and their use as monoamine neurotransmitter re-uptake inhibitors |
| MX2011004824A (es) | 2008-11-07 | 2012-01-12 | Triact Therapeutics Inc | Uso de derivados de butano catecólico en terapia contra el cáncer. |
| US20120189641A1 (en) | 2009-02-25 | 2012-07-26 | OSI Pharmaceuticals, LLC | Combination anti-cancer therapy |
| US20110171124A1 (en) | 2009-02-26 | 2011-07-14 | Osi Pharmaceuticals, Inc. | In situ methods for monitoring the EMT status of tumor cells in vivo |
| WO2010099138A2 (en) | 2009-02-27 | 2010-09-02 | Osi Pharmaceuticals, Inc. | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| JP2012519282A (ja) | 2009-02-27 | 2012-08-23 | オーエスアイ・ファーマシューティカルズ，エルエルシー | 間葉様腫瘍細胞またはその生成を阻害する薬剤を同定するための方法 |
| US8642834B2 (en) | 2009-02-27 | 2014-02-04 | OSI Pharmaceuticals, LLC | Methods for the identification of agents that inhibit mesenchymal-like tumor cells or their formation |
| US20120064072A1 (en) | 2009-03-18 | 2012-03-15 | Maryland Franklin | Combination Cancer Therapy Comprising Administration of an EGFR Inhibitor and an IGF-1R Inhibitor |
| CA2780875A1 (en) | 2009-11-13 | 2011-05-19 | Pangaea Biotech, S.L. | Molecular biomarkers for predicting response to tyrosine kinase inhibitors in lung cancer |
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Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL112249A (en) * | 1994-01-25 | 2001-11-25 | Warner Lambert Co | Pharmaceutical compositions containing di and tricyclic pyrimidine derivatives for inhibiting tyrosine kinases of the epidermal growth factor receptor family and some new such compounds |
| DE4431867A1 (de) * | 1994-09-07 | 1996-03-14 | Thomae Gmbh Dr K | Pyrimido[5,4-d]pyrimidine, diese Verbindungen enthaltende Arzneimittel, deren Verwendung und Verfahren zu ihrer Herstellung |
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- 1997-03-03 EP EP97907066A patent/EP0885226A1/de not_active Ceased
- 1997-03-03 HU HU9901820A patent/HUP9901820A3/hu unknown
- 1997-03-03 CZ CZ982817A patent/CZ281798A3/cs unknown
- 1997-03-03 CN CN97192787A patent/CN1212695A/zh active Pending
- 1997-03-03 PL PL97328771A patent/PL328771A1/xx unknown
- 1997-03-03 NZ NZ331546A patent/NZ331546A/xx unknown
- 1997-03-03 KR KR1019980706987A patent/KR19990087550A/ko not_active Application Discontinuation
- 1997-03-03 BR BR9708312A patent/BR9708312A/pt not_active IP Right Cessation
- 1997-03-03 SK SK1205-98A patent/SK120598A3/sk unknown
- 1997-03-03 AU AU19251/97A patent/AU710274B2/en not_active Ceased
- 1997-03-03 CA CA002243994A patent/CA2243994A1/en not_active Abandoned
- 1997-03-03 WO PCT/EP1997/001057 patent/WO1997032881A1/de not_active Application Discontinuation
- 1997-03-03 TR TR1998/01749T patent/TR199801749T2/xx unknown
- 1997-03-03 EE EE9800277A patent/EE9800277A/xx unknown
- 1997-03-03 JP JP9531444A patent/JP2000506847A/ja active Pending
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1998
- 1998-08-20 BG BG102708A patent/BG102708A/xx unknown
- 1998-09-04 NO NO984084A patent/NO984084D0/no unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008530212A (ja) * | 2005-02-16 | 2008-08-07 | シェーリング コーポレイション | Ｃｘｃｒ３アンタゴニスト活性を有するピペラジン−ピペリジン |
| JP2012510481A (ja) * | 2008-12-01 | 2012-05-10 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング | 癌に対するオータキシン阻害剤としての２，５−ジアミノ−置換ピリド［４，３−ｄ］ピリミジン |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ331546A (en) | 2000-03-27 |
| AU710274B2 (en) | 1999-09-16 |
| HUP9901820A2 (hu) | 1999-09-28 |
| EE9800277A (et) | 1999-02-15 |
| CN1212695A (zh) | 1999-03-31 |
| CZ281798A3 (cs) | 1999-02-17 |
| BG102708A (en) | 1999-09-30 |
| CA2243994A1 (en) | 1997-09-12 |
| KR19990087550A (ko) | 1999-12-27 |
| IL125404A0 (en) | 1999-03-12 |
| NO984084L (no) | 1998-09-04 |
| EP0885226A1 (de) | 1998-12-23 |
| BR9708312A (pt) | 1999-08-03 |
| WO1997032881A1 (de) | 1997-09-12 |
| NO984084D0 (no) | 1998-09-04 |
| AU1925197A (en) | 1997-09-22 |
| HUP9901820A3 (en) | 2001-10-29 |
| PL328771A1 (en) | 1999-02-15 |
| TR199801749T2 (xx) | 1998-12-21 |
| SK120598A3 (en) | 1999-06-11 |
| DE19629652A1 (de) | 1998-01-29 |
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