Characterization of the binding site of the histamine H3 receptor. 1. Various approaches to the synthesis of 2-(1H-imidazol-4-yl)cyclopropylamine and histaminergic activity of (1R,2R)-and (1S,2S)-2-(1H-imidazol-4-yl)-cyclopropylamine.

Various approaches to the synthesis of all four stereoisomers of 2-(1H- imidazol-4-yl)cyclopropylamine (cyclopropylhistamine) are described. The rapid and convenient synthesis and resolution of trans-cyclopropylhistamine is reported. The absolute configuration of its enantiomers was determined by single-crystal X-ray crystallographic analysis. The distinct transcyclopropylhistamine enantiomers were tested for their activity and affinity on the histamine

Synthesis and pharmacological evaluation of some amino-acid-containing cyproheptadine derivatives as dual antagonists of histamine H1- and leukotriene D4-receptors.

A novel series of cyproheptadine derivatives, in which an amino acid or a dipeptide moiety was introduced at the piperidine nitrogen, have been synthesized. The amino acid and dipeptide moieties were taken as part of leukotriene

Histamine H1 receptor ligands Part I. Novel thiazol-4-ylethanamine derivatives: synthesis and in vitro pharmacology.

A series of 2-substituted thiazol-4-ylethanamines have been synthesized and tested for their histaminergic

Evaluation of the receptor selectivity of the H₃ receptor antagonists, iodophenpropit and thioperamide: an interaction with the 5-HT₃ receptor revealed.

In the present study we evaluated the receptor selectivity of the potent histamine

Fragment based design of new H4 receptor-ligands with anti-inflammatory properties in vivo

Using a previously reported flexible alignment model we have designed, synthesized, and evaluated a series of compounds at the human histamine

Discovery of quinazolines as histamine H4 receptor inverse agonists using a scaffold hopping approach.

From a series of small fragments that was designed to probe the histamine H(4) receptor (H(4)R), we previously described quinoxaline-containing fragments that were grown into high affinity H(4)R ligands in a process that was guided by pharmacophore modeling. With a scaffold hopping exercise and using the same in silico models, we now report the identification and optimization of a series of quinazoline-containing H(4)R compounds. This approach led to the discovery of 6-chloro-N-(furan-3-ylmethyl)2-(4-methylpiperazin-1-yl)quinazolin-4-amine (VUF10499, 54) and 6-chloro-2-(4-methylpiperazin-1-yl)-N-(thiophen-2-ylmethyl)quinazolin-4-amine (VUF10497, 55) as potent human H(4)R inverse agonists (pK(i) = 8.12 and 7.57, respectively). Interestingly, both compounds also possess considerable affinity for the human histamine H(1) receptor (H(1)R) and therefore represent a novel class of dual action H(1)R/H(4)R ligands, a profile that potentially leads to added therapeutic benefit. Compounds from this novel series of quinazolines are antagonists at the rat H(4)R and were found to possess anti-inflammatory properties in vivo in the rat

Triazole ligands reveal distinct molecular features that induce H4R affinity and subtly govern H4R/H3R selectivity

The histamine