New hypocholesterolemic abietamide derivatives. II. Synthesis and hypocholesterolemic activity of N-phenyl-delta 8-dihydroabietamides.
A series of N-phenyl-delta 8-dihydroabietamide analogs were prepared and tested for hypocholesterolemic activity. The effects of substituents of the phenyl moiety on the activities were quantitatively analyzed by using various substituent parameters. The activities were enhanced by the electron-donating effect of ortho and para substitutents and the bulkiness of ortho substituents. A combination of 2,6-dimethylaniline with resin acids other than delta 8-dihydroabietic acid produced lower activities than N-(2,6-dimethylphenyl)-delta 8-dihydroabietamide, abietane-type carboxamides being somewhat stronger than pimarane-type carboxamides. The conversion of the carboxamide group to other groups resulted in more or less of a decrease in activity, giving evidence that the carboxamide group is important to hypocholesterolemic activity.
Fujita
Y
Y
Research Laboratories, Nippon Shinyaku Co., Ltd., Kyoto, Japan.
Yoshikuni
Y
Y
Sotomatsu
T
T
Mori
T
T
Ozaki
T
T
Sempuku
K
K
Ogino
A
A
Kise
M
M
Enomoto
H
H
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D000924:Anticholesteremic Agents / Q000138:chemical synthesis*; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D000577:Amides; D000924:Anticholesteremic Agents; D004224:Diterpenes