DE1172271B - Process for the preparation of xanthone-3-oxyacetic acid alkyl esters - Google Patents
Process for the preparation of xanthone-3-oxyacetic acid alkyl estersInfo
- Publication number
- DE1172271B DE1172271B DEC20599A DEC0020599A DE1172271B DE 1172271 B DE1172271 B DE 1172271B DE C20599 A DEC20599 A DE C20599A DE C0020599 A DEC0020599 A DE C0020599A DE 1172271 B DE1172271 B DE 1172271B
- Authority
- DE
- Germany
- Prior art keywords
- xanthone
- oxyacetic acid
- preparation
- alkyl esters
- acid alkyl
- 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
- 239000002253 acid Substances 0.000 title claims description 17
- 125000005907 alkyl ester group Chemical group 0.000 title claims description 5
- 238000000034 method Methods 0.000 title claims description 4
- 238000002360 preparation method Methods 0.000 title claims description 3
- 150000002148 esters Chemical class 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 14
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 7
- 125000004494 ethyl ester group Chemical group 0.000 description 7
- HSMPDPBYAYSOBC-UHFFFAOYSA-N khellin Chemical compound O1C(C)=CC(=O)C2=C1C(OC)=C1OC=CC1=C2OC HSMPDPBYAYSOBC-UHFFFAOYSA-N 0.000 description 7
- 229960002801 khellin Drugs 0.000 description 7
- 229960001789 papaverine Drugs 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- SXFPNMRWIWIAGS-UHFFFAOYSA-N Khellin Natural products COC1C2CCOC2C(OC)C3OC(C)CC(=O)C13 SXFPNMRWIWIAGS-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- JNELGWHKGNBSMD-UHFFFAOYSA-N xanthone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3OC2=C1 JNELGWHKGNBSMD-UHFFFAOYSA-N 0.000 description 2
- 206010003225 Arteriospasm coronary Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004351 coronary vessel Anatomy 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 230000000304 vasodilatating effect Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/78—Ring systems having three or more relevant rings
- C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
- C07D311/82—Xanthenes
- C07D311/84—Xanthenes with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 9
- C07D311/86—Oxygen atoms, e.g. xanthones
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
Verb wahren Herstellung von Xanthon-3-oxyessigsäurealkylestern Die Erfindung betrifft ein Verfahren zur Herstellung von Xanthon-3-oxyessigsäurealkylestern der allgemeinen Formel in der R einen Alkylrest bedeutet.Verb true Production of xanthone-3-oxyacetic acid alkyl esters The invention relates to a process for the production of xanthone-3-oxyacetic acid alkyl esters of the general formula in which R is an alkyl radical.
Diese neuen Verbindungen besitzen eine starke gefäßerweiternde Wirkung, insbesondere auf die Coronargefäße. Wie in Vergleichsversuchen festgestellt wurde, sind sie in dieser Hinsicht dem Papaverin und dem Khellin bei der Behandlung von Coronarspasmen eindeutig überlegen. These new compounds have a powerful vasodilator effect, especially on the coronary vessels. As was found in comparative tests, they are in this regard the Papaverine and the Khelline in treating Coronary spasms clearly superior.
Eine vergleichende Prüfung zwischen dem erfindungsgemäß hergestellten Xanthon-3-oxyessigsäureäthylester und dem aus dem Journal of the Chemical Society (London), 1956, S. 2142, bekannten Xanthon-1 -oxyessigsäureäthylester bezüglich der coronarerweiternden Wirkung nach der Methode von Kadatz, Arzneimittelforschung, 1959, S. 39, ergab, daß die erfindungsgemäß hergestellte Verbindung bei einer Dosierung von 50 y/kg bei Hunden eine Coronargefäßerweiterung von 94 °/0 für 3 Minuten zeigte, während mit dem bekannten Produkt keine sichere Wirkung feststellbar war. A comparative test between the one produced according to the invention Xanthone-3-oxyacetic acid ethyl ester and that from the Journal of the Chemical Society (London), 1956, p. 2142, known xanthone-1 -oxyacetic acid ethyl ester with respect to the coronary expanding effect according to the method of Kadatz, drug research, 1959, p. 39, showed that the compound prepared according to the invention with one dosage of 50 y / kg in dogs showed coronary vasodilation of 94 ° / 0 for 3 minutes, while with the known product no reliable effect could be determined.
Im Vergleich zu Papaverin und Khellin zeichnet sich der Xanthon-3-oxyessigsäureäthylester durch eine bedeutend geringere Toxizität aus. Bei intraperitonealer Injektion an Mäusen wurden folgende Toxizitätswerte erhalten: DLóo Papaverin ..... 0,24 g/kg Khellin . ...... 0,155 g/kg Xanthon-3-oxyessigsäureäthylester 0,9 g/kg Obwohl zur Erzielung gleicher gefäßerweiternder Wirkungen die doppelte Menge des Xanthon-3-oxyessigsäureäthylesters gegenüber Papaverin und die gleiche Menge gegenüber Khellin erforderlich ist, ergibt sich auf Grund der Toxizitätsunterschiede eine etwa doppelt so große therapeutische Breite für den Xanthon-3-oxyessigsäureäthylester im Vergleich zum Papaverin und eine etwa sechsfache therapeutische Breite im Vergleich zum Khellin. Außerdem ist die Wirkungsdauer der gleich wirksamen Dosen beim Xanthon-3-oxyessigsäureäthylester nahezu doppelt so lange wie beim Papaverin und um etwa 10°/0 länger als beim Khellin. Ferner bewirkt der Xanthon-3-oxyessigsäureäthylester in gleich wirksamer Dosierung eine viel geringere Blutdrucksenkung als Papaverin und Khellin (8 mm Hg gegenüber 33 bzw. 16 mm Hg). Compared to papaverine and khelline, xanthone-3-oxyacetic acid ethyl ester stands out by a significantly lower toxicity. With intraperitoneal injection on The following toxicity values were obtained in mice: DLóo papaverine ..... 0.24 g / kg Khellin. ...... 0.155 g / kg xanthone-3-oxyacetic acid ethyl ester 0.9 g / kg Although for Double the amount of xanthone-3-oxyacetic acid ethyl ester to achieve the same vasodilating effects to papaverine and the same amount to khelline is required Due to the differences in toxicity, the therapeutic one is about twice as large Width for the xanthone-3-oxyacetic acid ethyl ester compared to papaverine and about six times the therapeutic range compared to khellin. Also is the duration of action of the equally effective doses for ethyl xanthone-3-oxyacetate almost twice as much long as with papaverine and about 10% longer than with khelline. Furthermore, the xanthone-3-oxyacetic acid ethyl ester has an equally effective dosage a much smaller reduction in blood pressure than papaverine and khelline (8 mm Hg as opposed to 33 or 16 mm Hg).
Die Herstellung der Xanthon-3-oxyessigsäurealkylester der oben angegebenen allgemeinen Formel erfolgt dadurch, daß man 3-Oxyxanthon in an sich bekannter Weise mit Halogenessigsäureestern der Formel Hal CH2 - COOR, in der Hal ein Halogenatom darstellt und R die oben angegebene Bedeutung besitzt, umsetzt. The preparation of the xanthone-3-oxyacetic acid alkyl esters of the above general formula is made by using 3-oxyxanthone in a manner known per se with haloacetic acid esters of the formula Hal CH2 - COOR, in which Hal is a halogen atom represents and R has the meaning given above.
Beispiel Eine Mischung aus 8,5 g 3-Oxyxanthon, 7,5 g Bromessigsäureäthylester, 3 g wasserfreiem Kaliumcarbonat und 200 ccm Aceton wird 12 Stunden unter Rühren am Rückfluß erhitzt. Dann läßt man das erhaltene Reaktionsgemisch erkalten, saugt vom ausgeschiedenen Kaliumbromid ab und wäscht mit Aceton nach. Die vereinigten Filtrate werden bis zur Trockne abgedunstet, der verbleibende Rückstand wird mehrmals mit Wasser verrieben, jeweils abgesaugt und schließlich im Vakuumtrockenschrank getrocknet. Anschließend wird der erhaltene Rückstand aus Alkohol umkristallisiert. Es werden 9,5 g Xanthon-3-oxyessigsäureäthylester vom F. 122 bis 124"C erhalten. Example A mixture of 8.5 g of 3-oxyxanthone, 7.5 g of ethyl bromoacetate, 3 g of anhydrous potassium carbonate and 200 ccm of acetone are stirred for 12 hours heated to reflux. The reaction mixture obtained is then allowed to cool, and suction is applied of the precipitated potassium bromide and washes with acetone. The United Filtrates are evaporated to dryness, the remaining residue is several times rubbed with water, vacuumed off and finally in a vacuum drying cabinet dried. The residue obtained is then recrystallized from alcohol. 9.5 g of ethyl xanthone-3-oxyacetate with a melting point of 122 to 124 ° C. are obtained.
In der gleichen Weise werden bei Verwendung der entsprechenden Halogenessigsäurealkylester an Stelle von Bromessigsäureäthylester die folgenden Xanthon 3-oxyessigsäureester erhalten: Xanthon-3-oxyessigsäure-n-butylester, F. 102 bis 1040C; Xanthon-3-oxyessigsäure-i-propylester, F. 126 bis 127°C, Xanthon-3-oxyessigsäure-n-propylester, F. 116"C; Xanthon-3-oxyessigsäure-sec.butylester, F. 107 bis 108°C. In the same way when using the corresponding alkyl haloacetate instead of of ethyl bromoacetate the following xanthone 3-oxyacetic acid ester obtained: xanthone-3-oxyacetic acid n-butyl ester, m.p. 102 to 1040 ° C; I-propyl xanthone-3-oxyacetate, M.p. 126 to 127 ° C, xanthone-3-oxyacetic acid n-propyl ester, M.p. 116 "C; xanthone-3-oxyacetic acid sec.butyl ester, M.p. 107-108 ° C.
Claims (1)
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC20599A DE1172271B (en) | 1960-01-20 | 1960-01-20 | Process for the preparation of xanthone-3-oxyacetic acid alkyl esters |
| GB4413960A GB923132A (en) | 1960-01-20 | 1960-12-22 | New hydroxyxanthone derivatives |
| CH51761A CH392552A (en) | 1960-01-20 | 1961-01-17 | Process for the preparation of oxyxanthone derivatives |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DEC20599A DE1172271B (en) | 1960-01-20 | 1960-01-20 | Process for the preparation of xanthone-3-oxyacetic acid alkyl esters |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1172271B true DE1172271B (en) | 1964-06-18 |
Family
ID=7016832
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DEC20599A Pending DE1172271B (en) | 1960-01-20 | 1960-01-20 | Process for the preparation of xanthone-3-oxyacetic acid alkyl esters |
Country Status (3)
| Country | Link |
|---|---|
| CH (1) | CH392552A (en) |
| DE (1) | DE1172271B (en) |
| GB (1) | GB923132A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0175376A3 (en) * | 1984-09-21 | 1988-07-13 | Chugai Seiyaku Kabushiki Kaisha | Xanthone derivatives and process for producing the same |
-
1960
- 1960-01-20 DE DEC20599A patent/DE1172271B/en active Pending
- 1960-12-22 GB GB4413960A patent/GB923132A/en not_active Expired
-
1961
- 1961-01-17 CH CH51761A patent/CH392552A/en unknown
Non-Patent Citations (1)
| Title |
|---|
| None * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0175376A3 (en) * | 1984-09-21 | 1988-07-13 | Chugai Seiyaku Kabushiki Kaisha | Xanthone derivatives and process for producing the same |
| US4816479A (en) * | 1984-09-21 | 1989-03-28 | Chugai Seiyaku Kabushiki Kaisha | Xanthone derivatives and process for producing the same |
Also Published As
| Publication number | Publication date |
|---|---|
| CH392552A (en) | 1965-05-31 |
| GB923132A (en) | 1963-04-10 |
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