106243-16-7

Usage

Uses

Thioperamide is a highly potent and selective ligand for histamine H3-receptors.

Biological Activity

Potent histamine H 3 and H 4 antagonist/inverse agonist. K i values are 25 and 27 nM for human recombinant H 3 and H 4 receptors respectively. Blocks eosinophil shape change (IC 50 = 1.4 μ M) and chemotaxis (IC 50 = 519 nM) induced by histamine. Freely crosses the blood-brain barrier. Also available as part of the Histamine H 3 Receptor Tocriset? .

InChI:InChI=1/C15H24N4S/c20-15(18-13-4-2-1-3-5-13)19-8-6-12(7-9-19)14-10-16-11-17-14/h10-13H,1-9H2,(H,16,17)(H,18,20)

Upstream product

• 1122-82-3 isothiocyanatocyclohexane 
• 173469-32-4 1-(dimethylsulfamoyl)-4-<4-(4-hydroxy-1-tert-butoxycarbonyl)piperidyl>-(1H)-imidazole 
• 173469-30-2 4-<4-(4-hydroxy-1-tert-butoxycarbonyl)piperidyl>-(1H)-imidazole 
• 79099-07-3 N-tert-butyloxycarbonylpiperidin-4-one 
• 106243-23-6 4-(1H-imidazol-4-yl)-piperidine 

Downstream Products

• 149338-05-6 N-cyclohexyl-4-(5'-nitro-4'-imidazolyl)piperidine-1-carbothioamide 

Relevant academic research and scientific papers

Two Novel Syntheses of the Histamine H3 Antagonist Thioperamide

The previously described route for the synthesis of the histamine H3 antagonist thioperamide 3 has been improved considerably.Furthermore, two straightforward novel synthetic routes towards 3 are described herein.The last synthetic route (Scheme 3) is preferable as it is very suitable for the production of multigram quantities of thioperamide 3.

Design of potent non-thiourea H3-receptor histamine antagonists

Starting from thioperamide, the first potent and selective H3-receptor histamine antagonist, analogues have been synthesized and tested in vitro on rat cerebral cortex to explore structure-activity relationships. The aim has been to design potent compounds which do not possess the thiourea group of thioperamide and which may have improved brain penetration. In a short series of open chain thiourea analogues, the optimum chain length for H3- antagonist potency was found to be (CH2)3. Compounds derived from histamine and possessing an aromatic nitrogen-containing heterocycle on the side chain amino group in place of thiourea show H3-antagonist activity. Furthermore, when the heterocycle is 2-pyridyl, electron-withdrawing substituents (e.g. NO2, CF3, CO2Me) in the pyridine 5-position increased potency. The synthesis of 4-[4(5)-imidazolyl]piperidine and its conversion into the (trifluoromethyl)pyridyl analogue 5b of thioperamide is described; however, 5b is not as potent as thioperamide. Replacing imidazole by pyridine or substituting imidazole on the remote N considerably reduced potency. Replacing the side-chain NH by S increased potency still further and the most potent compound is 2-{[2-[4(5)-imidazolyl]ethyl]thio}-5-nitropyridine (UCL 1199) which has K(i) = 4.8 nM.