289902-97-2

Upstream product

• 102-46-5 4-(chloromethyl)-1,2-dimethylbenzene 
• 289902-87-0 diethyl 3,4-dimethylbenzylmalonate 
• 289902-93-8 3-azido-2-(3,4-dimethylbenzyl)propyl acetate 
• 289902-89-2 2-(3,4-dimethylbenzyl)-3-hydroxypropyl acetate 
• 289902-88-1 2-(3,4-dimethylbenzyl)-1,3-propanediol 

Downstream Products

• 289903-12-4 3-azido-2-(3,4-dimethylbenzyl)propyl pivalate 
• 735331-56-3 N-[3-azido-2-(3,4-dimethylbenzyl)propyl]phthalimide 
• 735331-59-6 tert-butyl N-(3-azido-2-(3,4-dimethylbenzyl)propyl)-N-[(tert-butoxycarbonyl)oxy]carbamate 
• 401573-58-8 N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxy-propyl]hydroxylamine 
• 1025985-78-7 2,2-dimethyl-propionic acid 2-(3,4-dimethyl-benzyl)-3-[3-(3-methoxy-4-methoxymethoxy-benzyl)-thioureido]-propyl ester 
• 735331-61-0 N-[3-azido-2-(3,4-dimethylbenzyl)propyl]-N-hydroxy-2,2-dimethylpropanamide 
• 735331-57-4 N-[3-azido-2-(3,4-dimethylbenzyl)propyl]-2,2-dimethylpropanamide 
• 735331-60-9 N-[3-azido-2-(3,4-dimethylbenzyl)propyl]hydroxylamine 
• 289903-16-8 3-azido-2-(3,4-dimethylbenzyl)propyl 3,4-dimethylbenzoate 

Relevant academic research and scientific papers

Vanilloid analogues containing resinferatoxin pharmacophores as potent vanilloid receptor agonists and analgesics, compositions and uses thereof

The present invention is related to new vanilloid analogues containing resiniferatoxin pharmacophores, pharmaceutical compositions comprising such analogues, and their uses as vanilloid receptor agonists and potent analgesics. The present invention provides a pharmaceutical composition for treating acute, chronic, inflammatory or neuropathic pains or for treating bladder hypersensitivity.

N-(3-acyloxy-2-benzylpropyl)-N′-(4-hydroxy-3-methoxybenzyl)thiourea derivatives as potent vanilloid receptor agonists and analgesics

A series of N-(3-acyloxy-2-benzylpropyl)-N′-(4-hydroxy-3-methoxybenzyl)thiourea derivatives were investigated as vanilloid receptor ligands in an effort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin, which includes the C20-homovanillic moiety, the C3-carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-inflammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with Ki values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also reflected by an excellent analgesic profile in animal tests with ED50 values of 0.5 μg/kg for 23 and 1.0 μg/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show significant anti-inflammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency.