1-pentyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, a selective aromatase inhibitor: in vivo studies.
1-Pentyl, 1-hexyl and 1-heptyl-3-(4-aminophenyl)pyrrolidine-2,5-dione, potent inhibitors of aromatase, lower oestrogen levels in PMSG-stimulated female rats in a comparable manner to the inhibitor aminoglutethimide (AG) used clinically for the treatment of breast cancer. Pharmacokinetic studies in the rat show t 1/2 values for the 1-hexyl compound and AG of 1.8 and 5.5 h respectively. In 4 tests for CNS-depressant activity the overall order of activity was AG > 1-heptyl = 1- hexyl >> 1-pentyl. The 1-pentyl compound has less tendency than AG to depress white cell and platelet counts in mice and overall is the drug candidate for further studies.
Whomsley
R
R
Welsh School of Pharmacy, University of Wales College of Cardiff, S. Glam., U.K.
Dahneem
A Y
AY
Nicholls
P J
PJ
Smith
H J
HJ
Ahmadi
M
M
Khalaf
L F
LF
D000616:Aminoglutethimide / Q000378:metabolism; D000818:Animals; D047072:Aromatase Inhibitors; D002490:Central Nervous System / Q000187:drug effects; D005260:Female; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats
C086122:1-pentyl-3-(4-aminophenyl)pyrrolidine-2,5-dione; D047072:Aromatase Inhibitors; D011760:Pyrrolidinones; D000616:Aminoglutethimide