CH507272A - Oxazolidinones inhibiting adrenergic beta-receptors - disease - Google Patents
Oxazolidinones inhibiting adrenergic beta-receptors - diseaseInfo
- Publication number
- CH507272A CH507272A CH1613068A CH1613068A CH507272A CH 507272 A CH507272 A CH 507272A CH 1613068 A CH1613068 A CH 1613068A CH 1613068 A CH1613068 A CH 1613068A CH 507272 A CH507272 A CH 507272A
- Authority
- CH
- Switzerland
- Prior art keywords
- formula
- compound
- dependent
- radical
- isopropylamino group
- Prior art date
Links
- IZXIZTKNFFYFOF-UHFFFAOYSA-N 2-Oxazolidone Chemical class O=C1NCCO1 IZXIZTKNFFYFOF-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 102000012740 beta Adrenergic Receptors Human genes 0.000 title abstract 2
- 108010079452 beta Adrenergic Receptors Proteins 0.000 title abstract 2
- 201000010099 disease Diseases 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title 1
- 230000002401 inhibitory effect Effects 0.000 title 1
- -1 isopropylamino group Chemical group 0.000 claims description 14
- 150000001875 compounds Chemical class 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- KNTZCGBYFGEMFR-UHFFFAOYSA-N (propan-2-ylazaniumyl)formate Chemical class CC(C)NC(O)=O KNTZCGBYFGEMFR-UHFFFAOYSA-N 0.000 claims description 5
- 150000008064 anhydrides Chemical class 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- GSLTVFIVJMCNBH-UHFFFAOYSA-N 2-isocyanatopropane Chemical compound CC(C)N=C=O GSLTVFIVJMCNBH-UHFFFAOYSA-N 0.000 claims description 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- ORGHESHFQPYLAO-UHFFFAOYSA-N vinyl radical Chemical compound C=[CH] ORGHESHFQPYLAO-UHFFFAOYSA-N 0.000 claims description 2
- 230000001419 dependent effect Effects 0.000 claims 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 3
- 125000003342 alkenyl group Chemical group 0.000 abstract 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 abstract 1
- 150000003254 radicals Chemical class 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 241000282326 Felis catus Species 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000700199 Cavia porcellus Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 206010003119 arrhythmia Diseases 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member 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 to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C07D263/24—Oxygen atoms attached in position 2 with hydrocarbon radicals, substituted by oxygen atoms, attached to other ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Oxazolidinones of general formula (I): R = alkenyl with minimum 2 and pref. max. 4C atoms Z = O or S. The new cpds. inhibit adrenergic beta-receptors and are also valuable intermediates in the prepn. of other pharmacologically active cpds. 3-Isopropyl 5-(o-allyloxy-phenoxymethyl)oxazolidinone-2 in particular has pronounced beta-blocking properties.
Description
Verfahren zur Herstellung von neuen Oxazolidin-2-on-verbindungen
Gegenstand der Erfindung ist ein Verfahren zur Herstellung von Oxazolidin-2-on-verbindungen der Formel
EMI1.1
worin R einen mindestens 2 und vorzugsweise nicht mehr als 4 Kohlenstoffatome aufweisenden niederen Alkenylrest bedeutet.
Der Rest R ist vorzugsweise der Vinylrest oder auch ein Propenyl- oder Butenylrest.
Die neuen Verbindungen besitzen wertvolle pharmakologische Eigenschaften. So hemmen sie insbesondere adrenerosche B-Rezeptoren, wie sich im Tierversuch, z.B. an Katzen und isolierten Meerschweinchenherzen zeigt. Die neuen Verbindungen können daher bei Angina pectoris oder Herzrhythmusstörungen Verwendung finden. Die neuen Verbindungen sind aber auch wertvolle Zwischenprodukte für die Herstellung von anderen nützlichen Stoffen, insbesondere von pharmakologisch wirksamen Verbindungen.
Besonders wertvoll bezüglich seiner pharmakologischen Eigenschaften ist das 3-Isopropyl-5-(o-allyloxy -p!lenoxy-methyl)-oxazolidinon-2 der Formel
EMI1.2
das beispielsweise an Katzen bei intravenöser Gabe in Dosen von 0,01 bis 0,1 mg/kg eine ausgesprochene 0-blok- kierende Wirkung aufweist.
Das erfindungsgemässe Verfahren zur Herstellung der neuen Verbindungen ist dadurch gekennzeichnet, dass man eine Verbindung der Formel
II
EMI1.3
intramolekular kondensiert, wobei R die oben genannte Bedeutung hat und einer der Reste X und Y die Isopropylaminogruppe und der andere einen gegen die Isopropylaminogruppe austauschbaren Rest bedeutet.
Ein gegen die Isopropylaminogruppe austauschbarer Rest X ist vor allem eine reaktionsfähig veresterte Hydroxylgruppe, wie besonders eine mit einer starken organischen oder anorganischen Säure, z.B. einer Halogenwasserstoffsäure, wie Chlor-, Brom- oder Jodwasserstoffsäure, oder mit einer Sulfonsäure, wie einer Arylsulfonsäure, z.B. der p-Toluolsulfonsäure, veresterte Hydroxylgruppe.
Ein gegen die Isopropylaminogruppe austauschbarer Rest Y ist vor allem eine reaktionsfähig veresterte Hydroxylgruppe, wie eine der oben genannten, oder eine Aminogruppe.
Ein erfindungsgemässer Ausgangsstoff kann auch in Form eines unter den Reaktionsbedingungen gebildeten rohen Gemisches verwendet werden, wie z.B. wenn man eine Verbindung der Formel
EMI2.1
worin R die oben genannte Bedeutung hat und X, einen gegen die Isopropylaminogruppe austauschbaren Rest, wie einen der oben genannten, bedeutet, mit einem reaktionsfähigen Derivat der Isopropylcarbaminsäure umsetzt.
Dabei entstehen intermediär die oben als Ausgangsstoffe genannten Verbindungen der Formel II, worin X einen gegen die Isopropylaminogruppe austauschbaren Rest bedeutet. Als reaktionsfähige Derivate der Isopropylcarbaminsäure sind vor allem Halogenide, besonders das Chlorid oder Bromid, oder Anhydride, vor allem das innere Anhydrid Isopropylaminoisocyanat, oder Ester zu erwähnen.
Die neuen Verbindungen können als Racemate oder in Form der Antipoden vorliegen. Die Racemate lassen sich in üblicher Weise in die Antipoden zerlegen. Vorteilhaft isoliert man den wirksameren Antipoden.
Die neuen Verbindungen können z.B. in Form pharmazeutischer Präparate Verwendung finden, welche sie in Mischung mit einem für die enterale oder parenterale Applikation geeigneten pharmazeutischen organischen oder anorganischen, festen oder flüssigen Trägermaterial enthalten.
Im folgenden Beispiel sind die Temperaturen in Cel siusvgraden angegeben.
Beispiel
Zu einer Lösung von 12 " l-Chlor-2-hydroxy-3-(o-allyl- oxyphenoxy)-propan in 100 ml Aceton gibt man 5 g-Isopropylisocyanat und 5 g fein gepulvertes Kaliumcarbonat. Nach 4stündigem Kochen werden die ungelösten Anteile filtriert, und das Filtrat dampft man im Vakuum ein. Den Rückstand kristallisiert man aus Methylenchlorid-Petroläther um, und erhält so das 3-Isopropyl-5 - < o-allyloxyphenoxymethyl)-oxazolidinon-(2) der Formel
EMI2.2
in Kristallen vom Fp. 58-600.
Process for the preparation of new oxazolidin-2-one compounds
The invention relates to a process for the preparation of oxazolidin-2-one compounds of the formula
EMI1.1
wherein R denotes a lower alkenyl radical having at least 2 and preferably not more than 4 carbon atoms.
The radical R is preferably the vinyl radical or a propenyl or butenyl radical.
The new compounds have valuable pharmacological properties. In particular, they inhibit adrenergic B receptors, as shown in animal experiments, e.g. shows on cats and isolated guinea pig hearts. The new compounds can therefore be used in angina pectoris or cardiac arrhythmias. The new compounds are also valuable intermediates for the production of other useful substances, in particular pharmacologically active compounds.
3-Isopropyl-5- (o-allyloxy-phenoxy-methyl) -oxazolidinone-2 of the formula is particularly valuable with regard to its pharmacological properties
EMI1.2
which, for example, when given intravenously in doses of 0.01 to 0.1 mg / kg in cats, has a pronounced 0-blocking effect.
The process according to the invention for preparing the new compounds is characterized in that a compound of the formula
II
EMI1.3
intramolecularly condensed, where R has the meaning given above and one of the radicals X and Y is the isopropylamino group and the other is a radical that can be exchanged for the isopropylamino group.
A radical X which can be exchanged for the isopropylamino group is above all a reactive esterified hydroxyl group, such as one with a strong organic or inorganic acid, e.g. with a hydrohalic acid such as hydrochloric, bromic or hydroiodic acid, or with a sulfonic acid such as an arylsulfonic acid, e.g. of p-toluenesulfonic acid, esterified hydroxyl group.
A radical Y which can be exchanged for the isopropylamino group is above all a reactive esterified hydroxyl group, such as one of the abovementioned, or an amino group.
A starting material according to the invention can also be used in the form of a crude mixture formed under the reaction conditions, e.g. when you have a compound of the formula
EMI2.1
where R has the abovementioned meaning and X, a radical which can be exchanged for the isopropylamino group, such as one of the abovementioned, is reacted with a reactive derivative of isopropylcarbamic acid.
The compounds of the formula II mentioned above as starting materials, in which X is a radical which can be exchanged for the isopropylamino group, are formed as intermediates. As reactive derivatives of isopropylcarbamic acid, halides, especially the chloride or bromide, or anhydrides, especially the internal anhydride isopropylaminoisocyanate, or esters are to be mentioned.
The new compounds can exist as racemates or in the form of the antipodes. The racemates can be broken down into the antipodes in the usual way. It is advantageous to isolate the more effective antipode.
The new compounds can e.g. in the form of pharmaceutical preparations which contain them as a mixture with a pharmaceutical, organic or inorganic, solid or liquid carrier material suitable for enteral or parenteral administration.
In the following example the temperatures are given in degrees Celsius.
example
5 g of isopropyl isocyanate and 5 g of finely powdered potassium carbonate are added to a solution of 12 "1-chloro-2-hydroxy-3- (o-allyl oxyphenoxy) propane in 100 ml of acetone. After boiling for 4 hours, the undissolved components are filtered and the filtrate is evaporated in vacuo, the residue is recrystallized from methylene chloride-petroleum ether to give 3-isopropyl-5- <o-allyloxyphenoxymethyl) -oxazolidinone- (2) of the formula
EMI2.2
in crystals of m.p. 58-600.
Claims (1)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1613068A CH507272A (en) | 1965-07-09 | 1965-11-17 | Oxazolidinones inhibiting adrenergic beta-receptors - disease |
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1432269A CH490405A (en) | 1965-07-09 | 1965-07-09 | Process for the preparation of new oxazolidine derivatives |
| CH962965A CH484172A (en) | 1965-07-09 | 1965-07-09 | Process for the preparation of a new oxazolidinone |
| CH1613068A CH507272A (en) | 1965-07-09 | 1965-11-17 | Oxazolidinones inhibiting adrenergic beta-receptors - disease |
| CH1585565A CH512504A (en) | 1965-07-09 | 1965-11-17 | Process for the preparation of new oxazolidin-2-one compounds |
| CH1585465A CH500216A (en) | 1965-07-09 | 1965-11-17 | 3-Isopropyl 5-phenoxymethyloxazolidines |
| CH505966A CH507271A (en) | 1965-07-09 | 1966-04-06 | Oxazolidinones inhibiting adrenergic beta-receptors |
| CH667066 | 1966-05-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CH507272A true CH507272A (en) | 1971-05-15 |
Family
ID=27561102
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CH1613068A CH507272A (en) | 1965-07-09 | 1965-11-17 | Oxazolidinones inhibiting adrenergic beta-receptors - disease |
Country Status (1)
| Country | Link |
|---|---|
| CH (1) | CH507272A (en) |
-
1965
- 1965-11-17 CH CH1613068A patent/CH507272A/en not_active IP Right Cessation
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PL | Patent ceased |