1287261-40-8

Upstream product

• 1223620-63-0 (S)-tert-butyl 7-(2-methoxy-2-oxoethoxy)-3-((4-methoxyphenyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 
• 73-32-5 L-isoleucine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 142335-41-9 (S)-2-(tert-butoxycarbonyl)-7-hydroxy-6,8-diiodo-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid 
• 142335-42-0 (3S)-2-(tert-butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydro-3-isoquinolinecarboxylic acid 
• 300-39-0 3,5-diiodo-l-tyrosine 
• 13139-16-7 N-(tert-butyloxycarbonyl)-L-isoleucine 
• 1287261-33-9 (S)-methyl 2-((3-((4-methoxyphenyl)carbamoyl)-1,2,3,4-tetrahydroisoquinolin-7-yl)oxy) acetate 
• 1223620-39-0 (S)-tert-butyl 7-hydroxy-3-((4-methoxyphenyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate 

Downstream Products

• 1287261-04-4 tert-butyl (2S,3S)-1-((S)-7-(2-(hydroxyamino)-2-oxoethoxy)-3-(4-methoxyphenylcarbamoyl)-3,4-dihydroisoquinolin-2(1H)-yl)-3-methyl-1-oxopentan-2-yl carbamate 
• 1287261-18-0 (S)-2-((2S,3S)-2-amino-3-methylpentanoyl)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide hydrochloride 
• 1314556-93-8 (S)-2-((2S,3S)-2-(3,3-dimethylbutanamido)-3-methylpentanoyl)-7-(2-(hydroxyamino)-2-oxoethoxy)-N-(4-methoxyphenyl)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide 

Relevant academic research and scientific papers

Discovery of a pair of diastereomers as potent HDACs inhibitors: Determination of absolute configuration, biological activity comparison and computational study

Histone deacetylase inhibitors (HDACi) are still the focus of epigenetic modulator development due to their effective intervention in many pathological processes. In our previous research, a potent HDACi was designed, synthesized and validated as a promising antitumor candidate named ZYJ-34c. Enlarged scale synthesis of ZYJ-34c for further detailed research was hindered by the occurrence of a by-product, which was identified as an isomer of ZYJ-34c by HRMS and 1H NMR. Subsequent synthesis route modification and optimization revealed that these two isomers were a pair of epimers and their absolute configurations could be directly determined by our optimized synthesis routes, through which each optically pure epimer could be stereoselectively synthesized, respectively. Based on these results, we concluded that our previously reported absolute configuration of ZYJ-34c was incorrect. It is worth noting that the epimer of ZYJ-34c exhibited more potent HDACs inhibition and both in vitro and in vivo antitumor activities, and moreover, their different HDACs inhibitory activities could be rationalized by computational simulations of their binding modes in HDAC2. The Royal Society of Chemistry 2013.

Development of tetrahydroisoquinoline-based hydroxamic acid derivatives: Potent histone deacetylase inhibitors with marked in vitro and in vivo antitumor activities

Inhibition of histone deacetylase (HDAC) results in growth arrest, differentiation, and apoptosis in nearly all tumor cell lines, promoting HDACs as promising targets for antitumor therapy. In our previous study we developed a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDAC inhibitors (HDACi), among which compound 7d exhibited promising HDAC8 inhibitory and antiproliferative activities. Herein, we report the design and development of a new class of tetrahydroisoquinoline-bearing hydroxamic acid analogues as potential HDACi and anticancer agents. In vitro biological evaluation of these compounds showed improved HDAC8 inhibition (compounds 31a and 31b exhibited mid-nM IC50 values against HDAC8) and potent growth inhibition in multiple tumor cell lines. Most importantly, compounds 25e, 34a, and 34b exhibited excellent in vivo anticancer activities in a human breast carcinoma (MDA-MB-231) xenograft model compared with suberoylanilide hydroxamic acid (SAHA), an approved HDACi. Collectively, our results indicate that tetrahydroisoquinoline bearing a hydroxamic acid is an excellent template to develop novel HDACi as potential anticancer agents.