Synthesis and pharmacological activity of fluorescent histamine H1 receptor antagonists related to mepyramine

Fluorescently labeled histamine H(1) receptor antagonists were synthesized starting from N-demethylmepyramine by introduction of omega-aminoalkyl chains (2-8 methylene groups in length) followed by derivatization of the terminal NH(2) group with various fluorophores (fluorescein, naphthofluorescein,...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2003-04, Vol.13 (7), p.1245-1248
Main Authors: LIANTAO LI, KRACHT, Julia, SHIQI PENG, BERNHARDT, Günther, BUSCHAUER, Armin
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain Neoplasms - metabolism
Fluorescent Dyes - chemical synthesis
Fluorescent Dyes - pharmacology
Fura-2 - analogs & derivatives
Fura-2 - chemistry
Glioblastoma - metabolism
Guinea Pigs
Histamine H1 Antagonists - chemical synthesis
Histamine H1 Antagonists - pharmacology
Humans
Ileum - drug effects
Ileum - metabolism
In Vitro Techniques
Indicators and Reagents
Medical sciences
Miscellaneous
Muscle Contraction - drug effects
Muscle, Smooth - drug effects
Muscle, Smooth - metabolism
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Pyrilamine - analogs & derivatives
Pyrilamine - chemical synthesis
Pyrilamine - pharmacology
Spectrophotometry, Ultraviolet
Tumor Cells, Cultured
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Fluorescently labeled histamine H(1) receptor antagonists were synthesized starting from N-demethylmepyramine by introduction of omega-aminoalkyl chains (2-8 methylene groups in length) followed by derivatization of the terminal NH(2) group with various fluorophores (fluorescein, naphthofluorescein, rhodamine, tetramethylrhodamine, BODIPY, dansyl, and nitrobenzoxadiazole (NBD)). On the isolated guinea pig ileum and in a Ca(2+) assay on U373MG human glioblastoma cells the highest H(1) antagonistic activities were found in 5- and 6-carboxyfluorescein labeled compounds with hexa- and octamethylene spacers and in an analogous NBD-aminohexanoyl derivative (pA(2) or pK(B) values in the range: 8.3-9.0; compared to 9.3-9.4 for mepyramine).
ISSN:0960-894X
1464-3405
DOI:10.1016/s0960-894x(03)00113-6