ES2346288T3 - 2,4-di(hetero-)arilamino(-oxi)-5-pirimidinas sustituidas como agentes antineoplasicos. - Google Patents
2,4-di(hetero-)arilamino(-oxi)-5-pirimidinas sustituidas como agentes antineoplasicos. Download PDFInfo
- Publication number
- ES2346288T3 ES2346288T3 ES01906021T ES01906021T ES2346288T3 ES 2346288 T3 ES2346288 T3 ES 2346288T3 ES 01906021 T ES01906021 T ES 01906021T ES 01906021 T ES01906021 T ES 01906021T ES 2346288 T3 ES2346288 T3 ES 2346288T3
- Authority
- ES
- Spain
- Prior art keywords
- alkyl
- amino
- substituted
- carbamoyl
- heterocyclic group
- 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.)
- Expired - Lifetime
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- 230000000118 anti-neoplastic effect Effects 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 212
- -1 hydroxy, mercapto Chemical class 0.000 claims abstract description 166
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 115
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 67
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 59
- 125000001424 substituent group Chemical group 0.000 claims abstract description 54
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 49
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 47
- 150000003230 pyrimidines Chemical class 0.000 claims abstract description 43
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 150000002148 esters Chemical class 0.000 claims abstract description 40
- 238000001727 in vivo Methods 0.000 claims abstract description 39
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 37
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 36
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 34
- 125000005843 halogen group Chemical group 0.000 claims abstract description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 34
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims abstract description 33
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 31
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 30
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims abstract description 29
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 20
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims abstract description 19
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims abstract description 18
- 125000004429 atom Chemical group 0.000 claims abstract description 18
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims abstract description 17
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 16
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 125000002619 bicyclic group Chemical group 0.000 claims abstract description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 12
- 125000005236 alkanoylamino group Chemical group 0.000 claims abstract description 11
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 10
- 125000002950 monocyclic group Chemical group 0.000 claims abstract description 10
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 8
- 239000001301 oxygen Substances 0.000 claims abstract description 8
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 8
- 239000011593 sulfur Substances 0.000 claims abstract description 8
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 8
- 125000004760 (C1-C4) alkylsulfonylamino group Chemical group 0.000 claims abstract description 7
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
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- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims abstract description 5
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004455 (C1-C3) alkylthio group Chemical group 0.000 claims abstract description 4
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- 238000000034 method Methods 0.000 claims description 107
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- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 9
- 230000006907 apoptotic process Effects 0.000 claims description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 9
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- 239000003814 drug Substances 0.000 claims description 9
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- 238000013508 migration Methods 0.000 claims description 8
- 230000035755 proliferation Effects 0.000 claims description 8
- 230000001093 anti-cancer Effects 0.000 claims description 7
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
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- PIEMJWXGWDBCMN-UHFFFAOYSA-N 2-[4-[(4-anilino-5-bromopyrimidin-2-yl)amino]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 PIEMJWXGWDBCMN-UHFFFAOYSA-N 0.000 claims 1
- WOWFEFJKHWCYLY-UHFFFAOYSA-N 4-n-[5-bromo-4-(6-methylpyridin-2-yl)pyrimidin-2-yl]-1-n-(2-piperidin-1-ylethyl)benzene-1,4-diamine Chemical compound CC1=CC=CC(C=2C(=CN=C(NC=3C=CC(NCCN4CCCCC4)=CC=3)N=2)Br)=N1 WOWFEFJKHWCYLY-UHFFFAOYSA-N 0.000 claims 1
- DUPNQUDKGLFCEW-UHFFFAOYSA-N 5-bromo-2-n-[4-(1-methylpiperidin-4-yl)oxyphenyl]-4-n-phenylpyrimidine-2,4-diamine Chemical compound C1CN(C)CCC1OC(C=C1)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 DUPNQUDKGLFCEW-UHFFFAOYSA-N 0.000 claims 1
- FLYWDADPUYSEFG-UHFFFAOYSA-N 5-bromo-2-n-[4-[2-(dimethylamino)ethoxy]phenyl]-4-n-phenylpyrimidine-2,4-diamine Chemical compound C1=CC(OCCN(C)C)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 FLYWDADPUYSEFG-UHFFFAOYSA-N 0.000 claims 1
- ARBYNWNBIKVNNJ-UHFFFAOYSA-N 5-bromo-2-n-[4-[3-(methylamino)prop-1-ynyl]phenyl]-4-n-phenylpyrimidine-2,4-diamine Chemical compound C1=CC(C#CCNC)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 ARBYNWNBIKVNNJ-UHFFFAOYSA-N 0.000 claims 1
- VGDBUSCPHQFLTB-UHFFFAOYSA-N 5-bromo-4-n-phenyl-2-n-[4-[2-(propan-2-ylamino)ethylamino]phenyl]pyrimidine-2,4-diamine Chemical compound C1=CC(NCCNC(C)C)=CC=C1NC1=NC=C(Br)C(NC=2C=CC=CC=2)=N1 VGDBUSCPHQFLTB-UHFFFAOYSA-N 0.000 claims 1
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- 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
- C07D239/28—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 with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C04—CEMENTS; CONCRETE; ARTIFICIAL STONE; CERAMICS; REFRACTORIES
- C04B—LIME, MAGNESIA; SLAG; CEMENTS; COMPOSITIONS THEREOF, e.g. MORTARS, CONCRETE OR LIKE BUILDING MATERIALS; ARTIFICIAL STONE; CERAMICS; REFRACTORIES; TREATMENT OF NATURAL STONE
- C04B35/00—Shaped ceramic products characterised by their composition; Ceramics compositions; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/622—Forming processes; Processing powders of inorganic compounds preparatory to the manufacturing of ceramic products
- C04B35/626—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B
- C04B35/63—Preparing or treating the powders individually or as batches ; preparing or treating macroscopic reinforcing agents for ceramic products, e.g. fibres; mechanical aspects section B using additives specially adapted for forming the products, e.g.. binder binders
- C04B35/632—Organic additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- 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
- C07D401/12—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 linked by a chain containing hetero atoms as chain links
-
- 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
- C07D403/02—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 two hetero rings
- C07D403/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Ceramic Engineering (AREA)
- Health & Medical Sciences (AREA)
- Inorganic Chemistry (AREA)
- Materials Engineering (AREA)
- Structural Engineering (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Hydrogenated Pyridines (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0004887.6A GB0004887D0 (en) | 2000-03-01 | 2000-03-01 | Chemical compounds |
| GB0004887 | 2000-03-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2346288T3 true ES2346288T3 (es) | 2010-10-14 |
Family
ID=9886703
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES01906021T Expired - Lifetime ES2346288T3 (es) | 2000-03-01 | 2001-02-26 | 2,4-di(hetero-)arilamino(-oxi)-5-pirimidinas sustituidas como agentes antineoplasicos. |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US6838464B2 (OSRAM) |
| EP (1) | EP1278735B1 (OSRAM) |
| JP (2) | JP2003525279A (OSRAM) |
| KR (2) | KR100855258B1 (OSRAM) |
| CN (1) | CN1220684C (OSRAM) |
| AT (1) | ATE472537T1 (OSRAM) |
| AU (2) | AU2001233979B2 (OSRAM) |
| BE (1) | BE2021C507I2 (OSRAM) |
| BR (1) | BR0108879A (OSRAM) |
| CA (1) | CA2398887C (OSRAM) |
| CY (2) | CY1111093T1 (OSRAM) |
| DE (1) | DE60142469D1 (OSRAM) |
| DK (1) | DK1278735T3 (OSRAM) |
| ES (1) | ES2346288T3 (OSRAM) |
| FR (1) | FR21C1010I2 (OSRAM) |
| GB (1) | GB0004887D0 (OSRAM) |
| HK (1) | HK1053111B (OSRAM) |
| IL (2) | IL150920A0 (OSRAM) |
| LU (1) | LUC00197I2 (OSRAM) |
| MX (1) | MXPA02007581A (OSRAM) |
| NO (2) | NO325443B1 (OSRAM) |
| NZ (1) | NZ520502A (OSRAM) |
| PT (1) | PT1278735E (OSRAM) |
| WO (1) | WO2001064656A1 (OSRAM) |
| ZA (1) | ZA200206192B (OSRAM) |
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