1383717-89-2

Upstream product

• 100-39-0 benzyl bromide 
• 10602-04-7 (4-ethynylphenyl)methanol 
• 22877-01-6 2,4-bis(benzyloxy)acetophenone 
• 89-84-9 2',4'-dihydroxy-4-acetophenone 
• 747414-16-0 (((4-(prop-1-en-2-yl)-1,3-phenylene)bis(oxy))bis(methylene))dibenzene 
• 1383717-80-3 2,4-bis-(benzyloxy)-5-isopropylaniline 
• 1383717-79-0 (((4-isopropyl-6-nitro-1,3-phenylene)bis(oxy))bis(methylene))dibenzene 
• 1383717-88-1 methyl 1-[2,4-bis(benzyloxy)cumenyl]-5-[p-(tert-butyldimethylsilyloxymethyl)phenyl]-1H-1,2,3-triazole-4-carboxylate 
• 1383717-87-0 methyl 3-(4-((tert-butyldimethylsilyloxy)methyl)phenyl)-prop-2-ynoate 
• 1383717-81-4 1,5-bis-benzyloxy-2-isopropyl-4-azido-benzene 
• 1155371-80-4 (((4-isopropyl-1,3-phenylene)bis(oxy))bis(methylene))dibenzene 
• 1093190-17-0 tert-butyl[(4-ethynylphenyl)methoxy]dimethylsilane 

Downstream Products

• 1383717-90-5 1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-(4-methanesulfonyloxy-methyl-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid methyl ester 
• 1383718-04-4 1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-{4-[(2-diethylamino-ethylamino)-methyl]-phenyl}-1H-[1,2,3]triazole-4-carboxylic acid methyl ester 
• 1383717-91-6 methyl 1-[2,4-bis(benzyloxy)cumenyl]-5-[p-(morpholin-4-ylmethyl)phenyl]-1H-1,2,3-triazole-4-carboxylate 
• 1383718-25-9 1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-(4-morpholin-4-ylmethyl-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid ethylamide 
• 1383718-03-3 methyl 1-[2,4-bis(benzyloxy)cumenyl]-5-[p-(bromomethyl)-phenyl]-1H-1,2,3-triazole-4-carboxylate 
• 1581709-46-7 C₃₀H₄₁N₅O₄ 
• 1383717-51-8 1-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-morpholin-4-ylmethylphenyl)-1H-[1,2,3]triazole-4-carboxylic acid cyclopentylamide 
• 1383717-52-9 1-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-morpholin-4-ylmethylphenyl)-1H-[1,2,3]triazole-4-carboxylic acid cyclohexylamide 
• 1383717-53-0 [1-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-morpholin-4-ylmethylphenyl)-1H-[1,2,3]triazol-4-yl]morpholin-4-ylmethanone 
• 1383717-54-1 (S)-2-{[1-(2,4-dihydroxy-5-isopropylphenyl)-5-(4-morpholin-4-ylmethylphenyl)-1H-[1,2,3]triazole-4-carbonyl]amino}-3-methylbutyric acid 
• 1581709-47-8 C₃₀H₄₀N₆O₆ 
• 1581709-48-9 C₂₉H₃₅N₅O₆ 
• 1581709-50-3 C₃₁H₄₁N₅O₆ 
• 1383717-92-7 (R,S)-1-(2,4-bis-benzyloxy-5-isopropyl-phenyl)-5-[4-(3-hydroxy-piperidin-1-ylmethyl)-phenyl]-1H-[1,2,3]triazole-4-carboxylic acid methyl ester 

Relevant academic research and scientific papers

Exploring in vitro and in vivo Hsp90 inhibitors activity against human protozoan parasites

A set of compounds, previously selected as potent Hsp90α inhibitors, has been studied on a panel of human parasites. 5-Aryl-3,4-isoxazolediamide derivatives (1) were active against two protozoa, Trypanosoma brucei rhodesiense and Plasmodium falciparum, with a good tolerability toward cytotoxicity on non-malignant L6 rat myoblast cell line, unlike the 1,5-diaryl,4-carboxamides-1,2,3-triazole derivatives (2) which, while showing a single-digit nM range activity against the same protozoa, were also highly cytotoxic on L6 cells. In a subsequent in vivo study, two isoxazolediamide derivatives, 1a and 1b, were very efficacious on the sleeping sickness-causing agent with a clear parasitaemia during treatment. These data, however, showed that not all protozoa are sensitive to Hsp90 inhibitors, as well as not all Hsp90 inhibitors are equally active on parasites.

Synthesis and evaluation of new Hsp90 inhibitors based on a 1,4,5-trisubstituted 1,2,3-triazole scaffold

Ruthenium catalyzed 1,3-cycloaddition (click chemistry) of an azido moiety installed on dihydroxycumene scaffold with differently substituted aryl propiolates gave a new family of 1,4,5-trisubstituted triazole carboxylic acid derivatives that showed high affinity toward Hsp90 associated with cell proliferation inhibition, both in nanomolar range. The 1,5 arrangement of the resorcinol, the aryl moieties, and the presence of an alkyl (secondary) amide in position 4 of the triazole ring were essential to get high activity. Docking simulations suggested that the triazoles penetrate the Hsp90 ATP binding site. Some 1,4,5-trisubstituted triazole carboxamides induced dramatic depletion of the examined client proteins and a very strong increase in the expression levels of the chaperone Hsp70. In vitro metabolic stability and in vivo preliminary studies on selected compounds have shown promising results comparable to the potent Hsp90 inhibitor NVP-AUY922. One of them, (compound 18, SST0287CL1) was selected for further investigation as the most promising drug candidate.

ARYL TRIAZOLE COMPOUNDS WITH ANTITUMOURAL ACTIVITY

The present invention relates to aryl triazole derivatives of Formula I having antitumoural activity through, as one possible biological target, the molecular chaperone heat shock protein 90 (Hsp90) inhibition. The invention includes the use of such compounds in medicine, in relation to cancer disease as well as other diseases where an inhibition of Hsp90 is responsive, and the pharmaceutical composition containing such compounds.