Pharmacological studies of 1-(p-chlorophenyl)propanol and 2-(1-hydroxy-3-butenyl)phenol: two new non-narcotic analgesics designed by molecular connectivity.
Molecular topology has been applied to the design of new analgesic drugs. Linear discriminant analysis and connectivity functions were used to design two potentially suitable drugs which were synthesized and tested for analgesic properties by the acetic acid-induced abdominal constriction test in mice and the tail-flick test in rats. In mice, the compound 1-(p-chlorophenyl)propanol showed higher analgesic activity, both intraperitoneally and orally, than acetylsalicylic acid. 2-(1-Hydroxy-3-butenyl)phenol exhibited a lesser protective effect (70% of that shown by acetylsalicylic acid). In rats, acetylsalicylic acid gave the greatest protection against pain when administered intraperitoneally, while 1-(p-chlorophenyl)propanol was the most active orally. The 2-(1-hydroxy-3-butenyl)phenol, both intraperitoneally and orally, showed the least protective effect. These results demonstrated the peripheral analgesic properties of the selected compounds, thus confirming the validity of the molecular design method.
García-March
F J
FJ
Departamento de Química Física, Facultad de Farmacia, Universidad de Valencia, España.
García-Domenech
R
R
Gálvez
J
J
Antón-Fos
G M
GM
de Julián-Ortiz
J V
JV
Giner-Pons
R
R
Recio-Iglesias
M C
MC
D000433:1-Propanol / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D000440:Butanols / Q000494:pharmacology; D015195:Drug Design; D005260:Female; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D020005:Propanols; D051381:Rats; D017208:Rats, Wistar
C105223:1-(4-chlorophenyl)-1-propanol; C105224:2-(1-hydroxy-3-butenyl)phenol; D018712:Analgesics, Non-Narcotic; D000440:Butanols; D010636:Phenols; D020005:Propanols; D000433:1-Propanol