Synthesis and binding affinities of fluoroalkylated raloxifenes.
Three fluoroalkylated derivatives (1-3) of the selective estrogen receptor modulator (SERM), raloxifene, have been synthesized. The key step in the synthesis is the C-C bond formation of benzo[b]thiophene and a substituted phenyl group (ring C) using a Stille reaction. The in vitro binding affinities of the substituted raloxifenes 1-3 are 45, 60, 89%, respectively, relative to the affinity of estradiol, which is higher than the affinity of raloxifene itself (25%). When labeled with the positron-emitting radionuclide, these compounds might be useful as PET imaging agents for estrogen receptor-positive breast tumors.
Lee
Kyo Chul
KC
Department of Chemistry, Inha University, 253 Yonghyundong, Namgu, 402-751, Inchon, South Korea.
Moon
Byung Seok
BS
Lee
Jae Hak
JH
Chung
Kyoo-Hyun
KH
Katzenellenbogen
John A
JA
Chi
Dae Yoon
DY
D005466:Fluorocarbons / Q000138:chemical synthesis* / Q000378:metabolism; D020849:Raloxifene Hydrochloride / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*
D005466:Fluorocarbons; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride