GB759174A - Improvements in diuretic acting xanthine derivatives - Google Patents
Improvements in diuretic acting xanthine derivativesInfo
- Publication number
- GB759174A GB759174A GB30304/53A GB3030453A GB759174A GB 759174 A GB759174 A GB 759174A GB 30304/53 A GB30304/53 A GB 30304/53A GB 3030453 A GB3030453 A GB 3030453A GB 759174 A GB759174 A GB 759174A
- Authority
- GB
- United Kingdom
- Prior art keywords
- xanthine
- ethyl
- general formula
- chloro
- thioxanthine
- 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
Links
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title abstract 10
- 239000002934 diuretic Substances 0.000 title 1
- 230000001882 diuretic effect Effects 0.000 title 1
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title 1
- -1 hydroxyalkyl radical Chemical class 0.000 abstract 20
- 229940075420 xanthine Drugs 0.000 abstract 7
- 125000004432 carbon atom Chemical group C* 0.000 abstract 6
- 229910052736 halogen Inorganic materials 0.000 abstract 6
- 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 abstract 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 3
- 239000005864 Sulphur Chemical group 0.000 abstract 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 3
- 150000002367 halogens Chemical class 0.000 abstract 3
- 238000000034 method Methods 0.000 abstract 3
- 229910052760 oxygen Inorganic materials 0.000 abstract 3
- 239000001301 oxygen Substances 0.000 abstract 3
- GIMNFISWKTZFKJ-UHFFFAOYSA-N 1,3-diethyl-7h-purine-2,6-dione Chemical compound O=C1N(CC)C(=O)N(CC)C2=C1NC=N2 GIMNFISWKTZFKJ-UHFFFAOYSA-N 0.000 abstract 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 abstract 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 abstract 2
- 150000001241 acetals Chemical class 0.000 abstract 2
- 229910052783 alkali metal Inorganic materials 0.000 abstract 2
- 125000000217 alkyl group Chemical group 0.000 abstract 2
- 150000001875 compounds Chemical class 0.000 abstract 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 abstract 2
- UKWHYYKOEPRTIC-UHFFFAOYSA-N mercury(ii) oxide Chemical compound [Hg]=O UKWHYYKOEPRTIC-UHFFFAOYSA-N 0.000 abstract 2
- 238000002360 preparation method Methods 0.000 abstract 2
- 239000000376 reactant Substances 0.000 abstract 2
- 159000000000 sodium salts Chemical class 0.000 abstract 2
- ZJYUREBTZZISRC-UHFFFAOYSA-N 1,3-diethyl-7-(2-oxopropyl)purine-2,6-dione Chemical compound O=C1N(CC)C(=O)N(CC)C2=C1N(CC(C)=O)C=N2 ZJYUREBTZZISRC-UHFFFAOYSA-N 0.000 abstract 1
- IIBMYGXJONJGLD-UHFFFAOYSA-N 1,3-dipropyl-2-sulfanylidene-7H-purin-6-one Chemical compound C(CC)N1C(=S)N(C=2N=CNC2C1=O)CCC IIBMYGXJONJGLD-UHFFFAOYSA-N 0.000 abstract 1
- JNOZGFXJZQXOSU-UHFFFAOYSA-N 1-chloro-2-methylpropan-2-ol Chemical compound CC(C)(O)CCl JNOZGFXJZQXOSU-UHFFFAOYSA-N 0.000 abstract 1
- VNBFUGOVQMFIRN-UHFFFAOYSA-N 1-chlorobutan-2-ol Chemical compound CCC(O)CCl VNBFUGOVQMFIRN-UHFFFAOYSA-N 0.000 abstract 1
- YYTSGNJTASLUOY-UHFFFAOYSA-N 1-chloropropan-2-ol Chemical compound CC(O)CCl YYTSGNJTASLUOY-UHFFFAOYSA-N 0.000 abstract 1
- LDLCZOVUSADOIV-UHFFFAOYSA-N 2-bromoethanol Chemical compound OCCBr LDLCZOVUSADOIV-UHFFFAOYSA-N 0.000 abstract 1
- OVXJWSYBABKZMD-UHFFFAOYSA-N 2-chloro-1,1-diethoxyethane Chemical compound CCOC(CCl)OCC OVXJWSYBABKZMD-UHFFFAOYSA-N 0.000 abstract 1
- VZIQXGLTRZLBEX-UHFFFAOYSA-N 2-chloro-1-propanol Chemical compound CC(Cl)CO VZIQXGLTRZLBEX-UHFFFAOYSA-N 0.000 abstract 1
- SZIFAVKTNFCBPC-UHFFFAOYSA-N 2-chloroethanol Chemical compound OCCCl SZIFAVKTNFCBPC-UHFFFAOYSA-N 0.000 abstract 1
- XKEHIUIIEXXHJX-UHFFFAOYSA-N 3-chlorobutan-2-ol Chemical compound CC(O)C(C)Cl XKEHIUIIEXXHJX-UHFFFAOYSA-N 0.000 abstract 1
- LAMUXTNQCICZQX-UHFFFAOYSA-N 3-chloropropan-1-ol Chemical compound OCCCCl LAMUXTNQCICZQX-UHFFFAOYSA-N 0.000 abstract 1
- SIJLYRDVTMMSIP-UHFFFAOYSA-N 4-Bromo-1-butanol Chemical compound OCCCCBr SIJLYRDVTMMSIP-UHFFFAOYSA-N 0.000 abstract 1
- AKMIPCJUTXDZKR-UHFFFAOYSA-N 4-chlorobutan-2-ol Chemical compound CC(O)CCCl AKMIPCJUTXDZKR-UHFFFAOYSA-N 0.000 abstract 1
- HXHGULXINZUGJX-UHFFFAOYSA-N 4-chlorobutanol Chemical compound OCCCCCl HXHGULXINZUGJX-UHFFFAOYSA-N 0.000 abstract 1
- PQJUJGAVDBINPI-UHFFFAOYSA-N 9H-thioxanthene Chemical group C1=CC=C2CC3=CC=CC=C3SC2=C1 PQJUJGAVDBINPI-UHFFFAOYSA-N 0.000 abstract 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 abstract 1
- 239000004215 Carbon black (E152) Substances 0.000 abstract 1
- 229920002261 Corn starch Polymers 0.000 abstract 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 abstract 1
- 239000005977 Ethylene Substances 0.000 abstract 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 abstract 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical class CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 abstract 1
- 235000021355 Stearic acid Nutrition 0.000 abstract 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 abstract 1
- 239000002253 acid Substances 0.000 abstract 1
- 239000011230 binding agent Substances 0.000 abstract 1
- 239000000969 carrier Substances 0.000 abstract 1
- 239000003638 chemical reducing agent Substances 0.000 abstract 1
- 239000003795 chemical substances by application Substances 0.000 abstract 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 abstract 1
- 239000008120 corn starch Substances 0.000 abstract 1
- 229940099112 cornstarch Drugs 0.000 abstract 1
- 235000014113 dietary fatty acids Nutrition 0.000 abstract 1
- 150000002148 esters Chemical class 0.000 abstract 1
- 150000002170 ethers Chemical class 0.000 abstract 1
- 239000000194 fatty acid Substances 0.000 abstract 1
- 229930195729 fatty acid Natural products 0.000 abstract 1
- 238000010438 heat treatment Methods 0.000 abstract 1
- 229910003439 heavy metal oxide Inorganic materials 0.000 abstract 1
- 229930195733 hydrocarbon Natural products 0.000 abstract 1
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000006460 hydrolysis reaction Methods 0.000 abstract 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract 1
- 239000008101 lactose Substances 0.000 abstract 1
- 229910000464 lead oxide Inorganic materials 0.000 abstract 1
- QDLAGTHXVHQKRE-UHFFFAOYSA-N lichenxanthone Natural products COC1=CC(O)=C2C(=O)C3=C(C)C=C(OC)C=C3OC2=C1 QDLAGTHXVHQKRE-UHFFFAOYSA-N 0.000 abstract 1
- 239000012280 lithium aluminium hydride Substances 0.000 abstract 1
- 235000019359 magnesium stearate Nutrition 0.000 abstract 1
- 229940101209 mercuric oxide Drugs 0.000 abstract 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 abstract 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 abstract 1
- YEXPOXQUZXUXJW-UHFFFAOYSA-N oxolead Chemical compound [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 238000011946 reduction process Methods 0.000 abstract 1
- 239000012279 sodium borohydride Substances 0.000 abstract 1
- 229910000033 sodium borohydride Inorganic materials 0.000 abstract 1
- 239000007787 solid Substances 0.000 abstract 1
- 239000008117 stearic acid Substances 0.000 abstract 1
- 125000001424 substituent group Chemical group 0.000 abstract 1
- 239000000454 talc Substances 0.000 abstract 1
- 229910052623 talc Inorganic materials 0.000 abstract 1
- 235000012222 talc Nutrition 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention comprises substituted xanthines of the general formula <FORM:0759174/IV(a)/1> wherein X represents oxygen or sulphur, Alk -OH represents a hydroxyalkyl radical containing 2 to 4 carbon atoms and R1 and R11 represent the same or different lower alkyl or alkenyl radicals which together contain at least 3 carbon atoms, and the preparation thereof by reacting a 1,3-dialkyl-xanthine or -thioxanthine of the general formula <FORM:0759174/IV(a)/2> wherein X, R1 and R11 have the above significance, or an alkali metal salt thereof, with a halogen hydrin of or an inner ether of an alkane diol having 2 to 4 carbon atoms, if necessary with the addition of acid binding agents, or by reacting a 1,3-dialkyl-xanthine or -thioxanthine of the above general formula, or an alkali metal salt thereof, with an ester of a halogen hydrin derived from an alkane diol having 2 to 4 carbon atoms and hydrolyzing the 7-acyloxyalkylxanthine- or -thioxanthine thus obtained to form the 7-hydroxyalkyl radical, or by reducing a 7-oxoalkyl-xanthine or -thioxanthine of the general formula <FORM:0759174/IV(a)/3> wherein m is 1, 2 or 3 and n is 0, 1 or 2 (the sum of m and n being at the most 3) and R1, R11 and X have the above significance, or a 7-carboxyalkyl-xanthine- or -thioxanthine of the general formula <FORM:0759174/IV(a)/4> wherein R represents a hydrocarbon radical, m is 1, 2 or 3 and R1, R11 and X have the above significance, the reducing agent in each case being lithium aluminium hydride or sodium borohydride or, in the case of a xanthine of the above general formula in which X is oxygen, by treating the corresponding compound in which X is sulphur with an inorganic desulphurizing agent, e.g. by heating with a heavy metal oxide such as mercuric oxide or lead oxide. Suitable halogen hydrins for use in the processes referred to above are ethylene-chlorohydrin and -bromohydrin, 2-chloro-1-propanol, 1-chloro- 2 - propanol, 3 - chloro - 1 - propanol, 1 - chloro- 2 - butanol, 3 - chloro - 2 - butanol, 4 - chloro- 2 - butanol, 4 - chloro - 1 - butanol, 4 - bromo- 1 - butanol, 1 - chloro - 2 - methyl - 2 - propanol, b -chloropropyl acetate, g -chloropropyl acetate and d -bromobutyl acetate. Suitable inner ethers for use in the process referred to above are ethylene and propylene oxides. Suitable 1,3-dialkyl-xanthines and -thioxanthines for use in the above processes are 1-methyl-3-ethyl-, 1- ethyl - 3 - methyl -, 1,3 - diethyl -, 1 - methyl- 3 - n - propyl -, 1 - ethyl - 3 - n - propyl, 1- ethyl - 3 - isopropyl -, 1,3 - di - n - propyl -, 1- methyl - 3 - n - butyl -, 1 - ethyl - 3 - n - butyl-, 1,3 - di - n - butyl -, 1,3 - di - isobutyl -, 1- ethyl - 3 - allyl -, 1 - allyl - 3 - ethyl -, and 1,3- diallyl - xanthene, 1 - methyl - 3 - ethyl -, 1,3- diethyl - and 1,3 - di - n - propyl - 2 - thioxanthine. Substituents which may be present in the 7-position of the xanthine and thioxanthine reactants for the reduction process are the b -oxoethyl, b -oxopropyl, g -oxopropyl, b -oxobutyl, a - methyl - b - oxopropyl, g - oxobutyl, carbethoxymethyl, a -carbethoxyethyl, b -carbethoxyethyl, a -carbomethoxypropyl and g -carboxypropyl groups. In the examples a number of substituted xanthines of the above general formula are prepared from reactants referred to above. The preparation of the following intermediate compounds is described. 7 - Oxoalkyl - and 7 - carboxyalkyl - xanthines and -thioxanthines of the general formula referred to above are prepared by reacting the corresponding N7-alkali metal compounds with acetals of the required halogen aldehydes followed by hydrolysis, or with the required halogen ketones or halogen fatty acid esters. In the examples 1,3-diethyl-7-acetonyl-xanthine is prepared by reacting the sodium salt of 1,3-diethyl-xanthine and monochloroacetone, and 1,3 - diethyl - 7 - (b - oxo - ethyl) - xanthine is prepared by reacting the sodium salt of 1,3-diethyl-xanthine and chloracetaldehyde diethyl acetal and hydrolysing the resulting acetal with hydrochloric acid.ALSO:A pharmaceutical preparation contains a solid carrier and a substituted xanthine of the general formula: <FORM:0759174/VI/1> wherein X represents oxygen or sulphur, AlkOH represents a hydroxyalkyl radical containing 2 to 4 carbon atoms and R1 and R11 represent the same or different lower alkyl or alkaryl radicals which together contain at least 3 carbon atoms. Suitable carriers are cornstarch, lactose, stearic acid, talc and magnesium stearate.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH759174X | 1952-11-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB759174A true GB759174A (en) | 1956-10-17 |
Family
ID=4534545
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB30304/53A Expired GB759174A (en) | 1952-11-07 | 1953-11-03 | Improvements in diuretic acting xanthine derivatives |
Country Status (1)
| Country | Link |
|---|---|
| GB (1) | GB759174A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS50101386A (en) * | 1974-01-22 | 1975-08-11 | ||
| EP0039780A1 (en) * | 1980-05-02 | 1981-11-18 | Societe Des Produits Nestle S.A. | Di- or trisubstituted xanthines with neuroleptic activity, process for their preparation and pharmaceutical preparations containing them |
| US4454138A (en) * | 1979-04-05 | 1984-06-12 | Johann A. Wuelfing | Xanthine derivatives and their use in pharmaceutical compositions |
-
1953
- 1953-11-03 GB GB30304/53A patent/GB759174A/en not_active Expired
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS50101386A (en) * | 1974-01-22 | 1975-08-11 | ||
| US4242345A (en) | 1974-01-22 | 1980-12-30 | Johann A. Wulfing | 7-(Oxoalkyl)-1,3-dialkyl xanthines, and medicaments containing them |
| JPS5912677B2 (en) * | 1974-01-22 | 1984-03-24 | ヨハン ア ウイルフイング | Production method of xanthine derivatives |
| US4454138A (en) * | 1979-04-05 | 1984-06-12 | Johann A. Wuelfing | Xanthine derivatives and their use in pharmaceutical compositions |
| EP0039780A1 (en) * | 1980-05-02 | 1981-11-18 | Societe Des Produits Nestle S.A. | Di- or trisubstituted xanthines with neuroleptic activity, process for their preparation and pharmaceutical preparations containing them |
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