[Synthesis and pharmacologic action of chiral fomocaine ((4-[2-methyl-3-(morpholin-4-yl)propyl)benzyl)-phenyl-ether and (4-(1-methyl-3-(morpholin-4-yl)propyl]benzyl)-phenyl-ether). 13. Synthesis of new compounds with local anesthetic action].
The syntheses of two chiral fomocaines namely rac ((4-[2-methyl-3-(morpholin-4-yl)propyl]-benzyl)-phenyl-ether (O/G 3) and rac (4-[1-methyl-3-(morpholin-4-yl)propyl]benzyl)-phenyl-ether) (O/G 5) are reported. These compounds are part of a new research program concerning the relation between chirality and local anaesthetic activity in the group of fomocaines. The yield over five steps is in the range of 9% (O/G 3) up to 19.2% (O/G 5). The racemates were resoluted via the diastereomeric salts formed with (+)- or (-)-camphersulfonic acid. The chromatographic resolution in analytical scale is successful using a Daicel OD-column. The enantiomers are stable. The surface anaesthesia of the racemates as well as of the enantiomeres is weaker in comparison with fomocaine. The rate of tissue irritation is higher. The LD50 (mouse i.v.) is in the range between 290-390 mg/kg, while fomocaine shows a LD50 value of 175 mg/kg.
Oelschläger
H
H
Institut für Pharmazie, Friedrich-Schiller-Universität, Jena, Germany.
Glassl
P
P
Seeling
A
A
Wange
J
J
Listing
M
M
Jung
B
B
D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001702:Biopharmaceutics; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007928:Lethal Dose 50; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects; D009025:Morpholines / Q000138:chemical synthesis* / Q000494:pharmacology; D010647:Phenyl Ethers / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013552:Swine
D000779:Anesthetics, Local; D004987:Ethers; D007202:Indicators and Reagents; D009025:Morpholines; D010647:Phenyl Ethers; C435331:fomocaine (4-(1-methyl-3-(morpholin-4-yl)propyl)benzyl)-phenyl-ether; C435330:fomocaine (4-(2-methyl-3-(morpholin-4-yl)propyl)benzyl)-phenyl-ether; C100275:fomocain
Synthese und pharmakologische Wirkung chiraler Fomocaine ((4-[2-Methyl-3-(morpholin-4-yl)propyl]benzyl)-phenyl-ether und (4-[1-Methyl-3-(morpholin-4-yl)propyl]benzyl)-phenyl-ether). 13. Mitteilung zur Synthese neuer Verbindungen mit lokalanästhetischer Wirkung.