Design and synthesis of a new type of non steroidal human aromatase inhibitors.
The structure-activity relationship study of one of recently described aromatase inhibitors, compound 1 (MR20814), allowed us to design some related derivatives as potential new inhibitors. Among those we synthesized, chlorophenylpyridylmethylenetetrahydroindolizinone 5 (MR20492) exhibited in vitro a ten-fold higher inhibition of the enzyme (IC50 = 0.2 +/- 0.0 microM and Ki = 10.3 +/- 3.3 nM).
Sonnet
P
P
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Laboratoire de Pharmacochimie, Caen, France.
Guillon
J
J
Enguehard
C
C
Dallemagne
P
P
Bureau
R
R
Rault S Auvray
P
P
Moslemi
S
S
Sourdiane
P
P
Galopin
S
S
Séralini
G E
GE
D047072:Aromatase Inhibitors; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D017316:Fadrozole / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008861:Microsomes / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry / Q000494:pharmacology
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007212:Indolizines; C116636:MR 20492; D011725:Pyridines; D014230:Triazoles; C060523:vorozole; D017316:Fadrozole