Synthesis of 5-keto-5-oxime derivatives of milbemycins and their activities against microfilariae.
Starting from milbemycin D (1), milbemycin A4 (2) and milbemycin A3 (3), a series of 5-keto-5-oxime derivatives were synthesized by selective oximation at the alpha,beta-conjugated carbonyl function of the 5-ketomilbemycins (4-6). The activities of the synthesized compounds were studied in dogs naturally infested with microfilariae of Dirofilaria immitis. The 5-keto-5-oximes of milbemycin D (7), A4 (8) and A3 (9) had quite high efficacy to control the microfilariae and more potency than their parents, while the 5-O-acyl oximes (11-15) also exhibited high activity.
Agricultural Chemicals Research Laboratories, Sankyo Co., Ltd., Shiga, Japan.
Y
Y
Tsukamoto
K
K
Sato
S
S
Mio
S
S
Sugai
T
T
Yanai
N
N
Kitano
S
S
Muramatsu
Y
Y
Nakada
J
J
Ide
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D004183:Dirofilaria immitis / Q000187:drug effects*; D004184:Dirofilariasis / Q000188:drug therapy*; D004285:Dogs; D018942:Macrolides; D008842:Microfilariae / Q000187:drug effects; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D018942:Macrolides; D010091:Oximes; C027837:moxidectin