Synthesis and aromatase-inhibitory activity of imidazolyl-1,3,5-triazine derivatives.
Triamino-substituted 1,3,5-triazine derivatives were synthesized and tested for inhibitory activities against the aromatase of human placental microsomes and the cytochrome P450 side chain cleavage of cholesterol (P450SCC) of pig adrenal mitochondria. The compounds having imidazolyl and tertiary amino groups as substituents in the 1,3,5-triazine ring showed significant aromatase-inhibitory activity. Among them, compounds 17, 23, 26, 27 and 28 were more active than the reference compound, CGS 16949A. The inhibitory activities of these compounds against P450SCC were much weaker than their aromatase-inhibitory activities. These compounds may be regarded as selective aromatase inhibitors.
Matsuno
T
T
Research Laboratory, Zenyaku Kogyo Co., Ltd., Tokyo, Japan.
Kato
M
M
Tsuchida
Y
Y
Takahashi
M
M
Yaguchi
S
S
Terada
S
S
D000311:Adrenal Glands / Q000201:enzymology; D000818:Animals; D047072:Aromatase Inhibitors; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D017316:Fadrozole / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000737:chemistry*; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D013552:Swine; D014227:Triazines / Q000737:chemistry*
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D007093:Imidazoles; D014227:Triazines; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017316:Fadrozole