DE2522369A1 - 5-fluoruracilderivate und verfahren zu ihrer herstellung - Google Patents
5-fluoruracilderivate und verfahren zu ihrer herstellungInfo
- Publication number
- DE2522369A1 DE2522369A1 DE19752522369 DE2522369A DE2522369A1 DE 2522369 A1 DE2522369 A1 DE 2522369A1 DE 19752522369 DE19752522369 DE 19752522369 DE 2522369 A DE2522369 A DE 2522369A DE 2522369 A1 DE2522369 A1 DE 2522369A1
- Authority
- DE
- Germany
- Prior art keywords
- fluorouracil
- substituted
- hydrogen
- radicals
- aryloxy
- 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.)
- Granted
Links
- 229960002949 fluorouracil Drugs 0.000 title claims abstract description 17
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 title claims abstract description 16
- 230000000259 anti-tumor effect Effects 0.000 title abstract 2
- 230000000694 effects Effects 0.000 title abstract 2
- 125000002252 acyl group Chemical group 0.000 claims abstract description 7
- 125000003435 aroyl group Chemical group 0.000 claims abstract description 7
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 7
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 238000006243 chemical reaction Methods 0.000 claims description 20
- -1 N1, N3-di- (p-chlorophenoxymethyl) -5-fluorouracil Chemical compound 0.000 claims description 13
- 150000001875 compounds Chemical class 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- 239000002585 base Substances 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- VMOGFYYUTKWVRU-UHFFFAOYSA-N 5-fluoro-1,3-bis(2-oxopropyl)pyrimidine-2,4-dione Chemical compound CC(=O)CN1C=C(F)C(=O)N(CC(C)=O)C1=O VMOGFYYUTKWVRU-UHFFFAOYSA-N 0.000 claims description 4
- 239000003513 alkali Substances 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- NKRIYFURUKACSD-UHFFFAOYSA-N 1-[(4-chlorophenoxy)methyl]-5-fluoropyrimidine-2,4-dione Chemical compound O=C1NC(=O)C(F)=CN1COC1=CC=C(Cl)C=C1 NKRIYFURUKACSD-UHFFFAOYSA-N 0.000 claims description 3
- 150000002366 halogen compounds Chemical class 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 3
- NXAGMTLJANMNIQ-UHFFFAOYSA-N 1,3-bis(ethoxymethyl)-5-fluoropyrimidine-2,4-dione Chemical compound CCOCN1C=C(F)C(=O)N(COCC)C1=O NXAGMTLJANMNIQ-UHFFFAOYSA-N 0.000 claims description 2
- OUAPULXYUWUOHW-UHFFFAOYSA-N 1-(ethoxymethyl)-5-fluoropyrimidine-2,4-dione Chemical compound CCOCN1C=C(F)C(=O)NC1=O OUAPULXYUWUOHW-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 239000000010 aprotic solvent Substances 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- SNKDCTFPQUHAPR-UHFFFAOYSA-N 1-fluoropyrimidine-2,4-dione Chemical class FN1C=CC(=O)NC1=O SNKDCTFPQUHAPR-UHFFFAOYSA-N 0.000 claims 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
- 208000009916 Yoshida Sarcoma Diseases 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 abstract 1
- 230000005764 inhibitory process Effects 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 238000001819 mass spectrum Methods 0.000 description 12
- RNHDAKUGFHSZEV-UHFFFAOYSA-N 1,4-dioxane;hydrate Chemical compound O.C1COCCO1 RNHDAKUGFHSZEV-UHFFFAOYSA-N 0.000 description 11
- 238000004458 analytical method Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 230000000704 physical effect Effects 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 229910001868 water Inorganic materials 0.000 description 3
- PJLGIZXAYTZSIZ-UHFFFAOYSA-N 1-chloro-4-(chloromethoxy)benzene Chemical compound ClCOC1=CC=C(Cl)C=C1 PJLGIZXAYTZSIZ-UHFFFAOYSA-N 0.000 description 2
- JQUPMZWYNQHLFM-UHFFFAOYSA-N 3-[(4-chlorophenoxy)methyl]-5-fluoro-1H-pyrimidine-2,4-dione Chemical compound O=C1C(F)=CNC(=O)N1COC1=CC=C(Cl)C=C1 JQUPMZWYNQHLFM-UHFFFAOYSA-N 0.000 description 2
- OIMRLHCSLQUXLL-UHFFFAOYSA-N 3-chlorobutan-2-one Chemical compound CC(Cl)C(C)=O OIMRLHCSLQUXLL-UHFFFAOYSA-N 0.000 description 2
- NEUUVOGLCVLUFS-UHFFFAOYSA-N 5-fluoro-1,3-bis(methoxymethyl)pyrimidine-2,4-dione Chemical compound COCN1C=C(F)C(=O)N(COC)C1=O NEUUVOGLCVLUFS-UHFFFAOYSA-N 0.000 description 2
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N DMSO-d6 Substances [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 239000002026 chloroform extract Substances 0.000 description 2
- FCYRSDMGOLYDHL-UHFFFAOYSA-N chloromethoxyethane Chemical compound CCOCCl FCYRSDMGOLYDHL-UHFFFAOYSA-N 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 2
- 235000019341 magnesium sulphate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- AVQQQNCBBIEMEU-UHFFFAOYSA-N 1,1,3,3-tetramethylurea Chemical compound CN(C)C(=O)N(C)C AVQQQNCBBIEMEU-UHFFFAOYSA-N 0.000 description 1
- FLAYZKKEOIAALB-UHFFFAOYSA-N 2-bromo-1-(4-chlorophenyl)ethanone Chemical compound ClC1=CC=C(C(=O)CBr)C=C1 FLAYZKKEOIAALB-UHFFFAOYSA-N 0.000 description 1
- VBUBPLAHIFBRJN-UHFFFAOYSA-N 3-(ethoxymethyl)-5-fluoro-1h-pyrimidine-2,4-dione Chemical compound CCOCN1C(=O)NC=C(F)C1=O VBUBPLAHIFBRJN-UHFFFAOYSA-N 0.000 description 1
- TVEXGJYMHHTVKP-UHFFFAOYSA-N 6-oxabicyclo[3.2.1]oct-3-en-7-one Chemical compound C1C2C(=O)OC1C=CC2 TVEXGJYMHHTVKP-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- 206010039491 Sarcoma Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- WBJINCZRORDGAQ-UHFFFAOYSA-N ethyl formate Chemical compound CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 description 1
- 230000009036 growth inhibition Effects 0.000 description 1
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 description 1
- FFASSIQWTSNOTM-UHFFFAOYSA-N methyl 3-[2-(1,3-dioxoisoindol-2-yl)ethyl]-6-fluoro-1h-indole-4-carboxylate Chemical compound O=C1C2=CC=CC=C2C(=O)N1CCC1=CNC2=C1C(C(=O)OC)=CC(F)=C2 FFASSIQWTSNOTM-UHFFFAOYSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
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
- C07D239/52—Two oxygen atoms
- C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
- C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other 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
- C07D239/553—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other 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 with halogen atoms or nitro radicals directly attached to ring carbon atoms, e.g. fluorouracil
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752522369 DE2522369A1 (de) | 1975-05-21 | 1975-05-21 | 5-fluoruracilderivate und verfahren zu ihrer herstellung |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19752522369 DE2522369A1 (de) | 1975-05-21 | 1975-05-21 | 5-fluoruracilderivate und verfahren zu ihrer herstellung |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE2522369A1 true DE2522369A1 (de) | 1976-12-02 |
| DE2522369C2 DE2522369C2 (enrdf_load_stackoverflow) | 1988-11-17 |
Family
ID=5947010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752522369 Granted DE2522369A1 (de) | 1975-05-21 | 1975-05-21 | 5-fluoruracilderivate und verfahren zu ihrer herstellung |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE2522369A1 (enrdf_load_stackoverflow) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6586440B2 (en) | 1990-07-19 | 2003-07-01 | Smithkline Beecham Corporation | Pharmaceutical compositions of 5-alkynyl uracil compounds |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5643913A (en) * | 1990-07-19 | 1997-07-01 | Glaxo Wellcome Inc. | Pharmaceutical compositions of 5-substituted uracil compounds |
| GB9020930D0 (en) | 1990-09-26 | 1990-11-07 | Wellcome Found | Pharmaceutical combinations |
-
1975
- 1975-05-21 DE DE19752522369 patent/DE2522369A1/de active Granted
Non-Patent Citations (8)
| Title |
|---|
| C.A. 75, 64 2389g * |
| C.A. 76, 25 560g * |
| C.A. 82, 106174t * |
| Chem. Lett., 1975, S.129 (=C.A.83, 9973r) * |
| EHRHARDT/RUSCHIG: ArzneimittelV, 1972, S.368 * |
| J. Med. Sci. 23, 1974, S.51 (=C.A. 83, 108468m) * |
| JP 1 27 986-74 (=C.A. 83, 10135a) * |
| JP 37 787-75 (=C.A. 84, 17405t) * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6586440B2 (en) | 1990-07-19 | 2003-07-01 | Smithkline Beecham Corporation | Pharmaceutical compositions of 5-alkynyl uracil compounds |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2522369C2 (enrdf_load_stackoverflow) | 1988-11-17 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8110 | Request for examination paragraph 44 | ||
| 8127 | New person/name/address of the applicant |
Owner name: FUJII, SETSURO, KYOTO, JP |
|
| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition |