Parallel fluorescent probe synthesis based on the large-scale preparation of BODIPY FL propionic acid.
We describe a methodology for quick development of fluorescent probes with the desired potency for the target of interest by using a method of parallel synthesis, termed as Parallel Fluorescent Probe Synthesis (Parallel-FPS). BODIPY FL propionic acid 1 is a widely used fluorophore, but it is difficult to prepare a large amount of 1, which hinders its use in parallel synthesis. Optimization of a synthetic scheme enabled us to obtain 50g of 1 in one batch. With this large quantity of 1 in hand, we performed Parallel-FPS of BODIPY FL-labeled ligands for estrogen related receptor-α (ERRα). An initial trial of the parallel synthesis with various linkers provided a potent ligand for ERRα (Reporter IC50=80nM), demonstrating the usefulness of Parallel-FPS.
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Taisuke
T
Katoh
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Masato
M
Yoshikawa
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Takeshi
T
Yamamoto
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Ryosuke
R
Arai
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Noriyuki
N
Nii
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Yoshihide
Y
Tomata
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Shinkichi
S
Suzuki
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Ryoukichi
R
Koyama
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.
Nobuyuki
N
Negoro
Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. Electronic address: takatoshi.yogo@takeda.com.
Takatoshi
T
Yogo
D001896:Boron Compounds / Q000737:chemistry*; D005456:Fluorescent Dyes / Q000138:chemical synthesis*; D008024:Ligands; D011422:Propionates / Q000737:chemistry*; D011960:Receptors, Estrogen / Q000737:chemistry; D000097983:ERRalpha Estrogen-Related Receptor
D001896:Boron Compounds; D005456:Fluorescent Dyes; D008024:Ligands; D011422:Propionates; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C095489:4,4-difluoro-4-bora-3a,4a-diaza-s-indacene; C029658:propionic acid
BODIPY FL propionic acid; Bulk preparation; ERRα; Parallel fluorescent probe synthesis