708261-27-2

Upstream product

• 289902-95-0 3-azido-2-(4-t-butylbenzyl)propyl acetate 
• 289902-91-6 2-(4-t-butylbenzyl)-3-hydroxypropyl acetate 
• 289903-00-0 3-azido-2-(4-t-butylbenzyl)-1-propanol 
• 172477-52-0 2-(4-tert-butylbenzyl)-1,3-propanediol 
• 19692-45-6 4-tert-butylbenzyl chloride 
• 37765-76-7 2-(4-tert-butylbenzyl)diethylmalonate 
• 289903-22-6 3-azido-2-(4-t-butylbenzyl)propyl pivalate 

Downstream Products

• 289903-41-9 N-[3-pivaloyloxy-2-(4-t-butylbenzyl)propyl]-2-(4-hydroxy-3-methoxyphenyl)acetamide 
• 289903-60-2 2,2-Dimethyl Propionic Acid 2-{3-[4-(2-Azidoethoxy)-3-methoxybenzyl]thioureido Methyl}-3-(4-t-butylphenyl)propyl Ester 
• 928673-07-8 2,2-dimethyl-propionic acid 3-(4-tert-butyl-phenyl)-2-[3-(3-chloro-5-methoxy-4-methoxymethoxy-benzyl)-thioureidomethyl]-propyl ester 
• 928673-11-4 2,2-dimethyl-propionic acid 2-[3-(2-bromo-5-methoxy-4-methoxymethoxy-benzyl)-thioureidomethyl]-3-(4-tert-butyl-phenyl)-propyl ester 
• 928673-10-3 2,2-dimethyl-propionic acid 3-(4-tert-butyl-phenyl)-2-[3-(2-chloro-5-methoxy-4-methoxymethoxy-benzyl)-thioureidomethyl]-propyl ester 
• 928673-12-5 2,2-dimethyl-propionic acid 3-(4-tert-butyl-phenyl)-2-[3-(2-iodo-5-methoxy-4-methoxymethoxy-benzyl)-thioureidomethyl]-propyl ester 
• 1258845-88-3 2-(4-tert-butylbenzyl)-3-[2-(4-amino-3,5-dibromophenyl)acetamido]propyl pivalate 
• 1258845-82-7 2-(4-tert-butylbenzyl)-3-[2-(4-amino-3-methoxyphenyl)acetamido]propyl pivalate 
• 1258845-83-8 2-(4-tert-butylbenzyl)-3-[2-(4-amino-3-chloro-5-methoxyphenyl)acetamido]propyl pivalate 
• 1258845-84-9 2-(4-tert-butylbenzyl)-3-[2-(4-amino-3-bromo-5-methoxyphenyl)acetamido]propyl pivalate 
• 1258845-90-7 2-(4-tert-butylbenzyl)-3-[2-(2-bromo-4-methanesulfonylamino-5-methoxyphenyl)acetamido]-propyl pivalate 
• 1258845-62-3 2-(4-tert-butylbenzyl)-3-[2-(3-chloro-4-hydroxy-5-methoxyphenyl)acetamido]propyl pivalate 
• 1258845-63-4 2-(4-tert-butylbenzyl)-3-[2-(3-bromo-4-hydroxy-5-methoxyphenyl)acetamido]propyl pivalate 
• 1258845-64-5 2-(4-tert-butylbenzyl)-3-[2-(4-hydroxy-3-iodo-5-methoxyphenyl)acetamido]propyl pivalate 

Relevant academic research and scientific papers

N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea analogues: Novel potent and high affinity antagonists and partial antagonists of the vanilloid receptor

Isosteric replacement of the phenolic hydroxyl group in potent vanilloid receptor (VR1) agonists with the alkylsulfonamido group provides a series of compounds which are effective antagonists to the action of the capsaicin on rat VR1 heterologously expressed in Chinese hamster ovary (CHO) cells. In particular, compound 61, N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N′-[3-fluoro-4- (methylsulfonylamino)benzyl]thiourea was a full antagonist against capsaicin, displayed a Ki value of 7.8 nM (compared to 520 nM for capsazepine and 4 nM for 5-iodoRTX), and showed excellent analgesic activity in mice. Structure-activity analysis of the influence of modifications in the A- and C-regions of 4-methylsulfonamide ligands on VR1 agonism/antagonism indicated that 3-fluoro substitution in the A-region and a 4-tert-butylbenzyl moiety in the C-region favored antagonism, whereas a 3-methoxy group in the A-region and 3-acyloxy2-benzylpropyl moieties in the C-region favored agonism.

Phenolic modification as an approach to improve the pharmacology of the 3-acyloxy-2-benzylpropyl homovanillic amides and thioureas, a promising class of vanilloid receptor agonists and analgesics

In order to improve the analgesic activity and pharmacokinetics of thioureas 2 and 3, which we previously developed as potent vanilloid receptor (VR) agonists, we prepared and characterized phenolic modifications of them and of their amide surro-gates (7, 8). The aminoethyl analogue of the amide template 13 was a potent analgesic with an EC50 =0.96 μg/kg in the AA-induced writhing test and with better in vivo stability than the parent phenol. Copyright

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.