New aromatase inhibitors. Synthesis and biological activity of aryl-substituted pyrrolizine and indolizine derivatives.
We report herein the design and the synthesis of some aryl-substituted pyrrolizine and indolizine derivatives, on the basis of a hypothetical pharmacophore structure designed to fit the catalytic site of the human cytochrome P450 aromatase. The in vitro biological evaluation of these compounds allowed us to point out two new potent non-steroidal aromatase inhibitors, MR 20494 and MR 20492, with IC50 values in the range of 0.1 microM.
Sonnet
P
P
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Laboratoire de Pharmacochimie, UFR des Sciences Pharmaceutiques, Caen, France.
Dallemagne
P
P
Guillon
J
J
Enguehard
C
C
Stiebing
S
S
Tanguy
J
J
Bureau
R
R
Rault
S
S
Auvray
P
P
Moslemi
S
S
Sourdaine
P
P
Séralini
G E
GE
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D010920:Placenta / Q000201:enzymology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D007212:Indolizines; D011758:Pyrroles; C035094:indolizine