omega-Dialkylaminoalkyl ethers of 6-(benzyl or phenyl)-1,3,3-trimethyl-2-oxabicyclo [2.2.2]octan-6-ol with platelet antiaggregating and local anesthetic activities.
The synthesis of 1,3,3-trimethyl-6-phenyl-2-oxabicyclo[2.2.2]octan-6-ol 2 and 6-benzyl-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-ol 3 starting from (+)-1,3,3-trimethyl-2-oxabicyclo[2.2.2]octan-6-one and phenylmagnesium bromide or benzylmagnesium chloride, respectively, is described. Alcohols 2 and 3 gave a series of omega-dialkylaminoalkyl ethers 4 by reaction as sodium salts with omega-chloroalkyldialkylamines in toluene solution. Some compounds 4, in particular those derived from alcohol 2, showed a strong platelet antiaggregating activity in vitro, superior to that of acetylsalicylic acid, as well as in general an appreciable local anesthetic activity and a weak sedative effect in mice.
Schenone
S
S
Istituto di Scienze Farmaceutiche dell'Università Viale Benedetto XV, Genova, Italy.
Bruno
O
O
Ranise
A
A
Bondavalli
F
F
Cenicola
M L
ML
Losasso
C
C
Carnevale
M
M
Ottavo
R
R
D'Antonio
M
M
D000758:Anesthesia; D000779:Anesthetics, Local / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002725:Chloroform; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013055:Spectrophotometry, Infrared; D014693:Ventricular Fibrillation / Q000139:chemically induced / Q000517:prevention & control
D000779:Anesthetics, Local; D001643:Bridged Bicyclo Compounds; D010975:Platelet Aggregation Inhibitors; D002725:Chloroform