PMID- 10683870
OWN - NLM
STAT- MEDLINE
DCOM- 20000328
LR  - 20141120
IS  - 0031-7144 (Print)
IS  - 0031-7144 (Linking)
VI  - 55
IP  - 1
DP  - 2000 Jan
TI  - Fluorescent-labeled ligands for the benzodiazepine receptor. Part 1: Synthesis 
      and characterization of fluorescent-labeled benzodiazepines.
PG  - 42-8
AB  - Because radioactive labeled ligands in receptor assays have several 
      disadvantages, we synthesized a number of fluorescent-labeled benzodiazepines. 
      Several fluorophores were attached at different positions of 1,4-benzodiazepine 
      molecules in order to assess the impact of the fluorophores and their coupling 
      position on the affinity for the benzodiazepine receptor. Besides the 
      1,4-benzodiazepines, the 1,2-annelated 1,4-benzodiazepines were also used for 
      labeling. A metabolite of flumazenil (18), desethylflumazenil (Ro15-3890, 19), 
      was labeled with the fluorophore 4-bromomethyl-7-methoxycoumarin, with and 
      without the incorporation of a spacer chain, yielding the methyl-methoxycoumarin 
      (Mmc) derivatives Mmc-Ro15-3890 (20a) and Mmc-O-CO-(CH2)3-Ro15-3890 (20b), 
      respectively. After the synthesis, the fluorescent-labeled benzodiazepines were 
      purified by HPLC, using an analytical RP-C18 column. For the purification of 20b, 
      the chromatographic system was optimized, using multi-criteria decision making 
      (MCDM) techniques. The binding affinities for the benzodiazepine receptor and the 
      fluorescence characteristics were determined for the resulting products.
FAU - Janssen, M J
AU  - Janssen MJ
AD  - Department of Analytical Chemistry and Toxicology, University Centre for 
      Pharmacy, Wageningen, The Netherlands.
FAU - Hulst, R
AU  - Hulst R
FAU - Kellogg, R M
AU  - Kellogg RM
FAU - Hendriks, M M
AU  - Hendriks MM
FAU - Ensing, K
AU  - Ensing K
FAU - de Zeeuw, R A
AU  - de Zeeuw RA
LA  - eng
PT  - Journal Article
PL  - Germany
TA  - Pharmazie
JT  - Die Pharmazie
JID - 9800766
RN  - 0 (Fluorescent Dyes)
RN  - 0 (GABA Modulators)
RN  - 0 (Ligands)
RN  - 0 (Receptors, GABA-A)
RN  - 12794-10-4 (Benzodiazepines)
RN  - 40P7XK9392 (Flumazenil)
SB  - IM
MH  - Animals
MH  - Benzodiazepines/*chemical synthesis/chemistry
MH  - Brain Chemistry
MH  - Cattle
MH  - Chromatography, High Pressure Liquid
MH  - Flumazenil/chemistry
MH  - Fluorescent Dyes/*chemical synthesis
MH  - GABA Modulators/chemistry
MH  - In Vitro Techniques
MH  - Ligands
MH  - Magnetic Resonance Spectroscopy
MH  - Membranes/metabolism
MH  - Radioligand Assay
MH  - Receptors, GABA-A/*drug effects/metabolism
MH  - Spectrophotometry, Ultraviolet
EDAT- 2000/02/23 09:00
MHDA- 2000/04/01 09:00
CRDT- 2000/02/23 09:00
PHST- 2000/02/23 09:00 [pubmed]
PHST- 2000/04/01 09:00 [medline]
PHST- 2000/02/23 09:00 [entrez]
PST - ppublish
SO  - Pharmazie. 2000 Jan;55(1):42-8.