1353182-61-2

Upstream product

• 2550-36-9 Cyclohexylmethyl bromide 
• 442-51-3 harmine 
• 487-03-6 harmol 

Downstream Products

• 1353182-81-6 1-methyl-2-(2-fluorobenzyl)-7-cyclohexylmethyloxy-9-cyclohexylmethyl-β-carbolin-2-ium bromide 
• 1353182-75-8 1-methyl-2-benzyl-7-cyclohexylmethyloxy-9-cyclohexylmethyl-β-carbolin-2-ium bromide 
• 1353182-85-0 1-methyl-2-(4-fluorobenzyl)-7-cyclohexylmethyloxy-9-cyclohexylmethyl-β-carbolin-2-ium bromide 

Relevant academic research and scientific papers

Identification and Repurposing of Trisubstituted Harmine Derivatives as Novel Inhibitors of Mycobacterium tuberculosis Phosphoserine Phosphatase

Mycobacterium tuberculosis is still the deadliest bacterial pathogen worldwide and the increasing number of multidrug-resistant tuberculosis cases further complicates this global health issue. M. tuberculosis phosphoserine phosphatase SerB2 is a promising target for drug design. Besides being a key essential metabolic enzyme of the pathogen’s serine pathway, it appears to be involved in immune evasion mechanisms. In this work, a malachite green-based phosphatase assay has been used to screen 122 compounds from an internal chemolibrary. Trisubstituted harmine derivatives were found among the best hits that inhibited SerB2 activity. Synthesis of an original compound helped to discuss a brief structure activity relationship evaluation. Kinetics experiments showed that the most potent derivatives inhibit the phosphatase in a parabolic competitive fashion with apparent inhibition constants (Ki) values in the micromolar range. Their interaction modes with the enzyme were investigated through induced fit docking experiments, leading to results consistent with the experimental data. Cellular assays showed that the selected compounds also inhibited M. tuberculosis growth in vitro. Those promising results may provide a basis for the development of new antimycobacterial agents targeting SerB2.

Novel trisubstituted harmine derivatives with original in vitro anticancer activity

To overcome the intrinsic resistance of cancer cells to apoptotic stimuli, we designed and synthesized approximately 50 novel β-carbolines structurally related to harmine. Harmine is known for its anticancer properties and is a DYRK1A inhibitor. Of the synthesized compounds, the most active in terms of growth inhibition of five cancer cell lines are cytostatic and approximately 100 times more potent than harmine but demonstrated no DYRK1A inhibitory activity. These novel β-carbolines display similar growth inhibitory activity in cancer cells that are sensitive and resistant to apoptotic stimuli. Using ChemGPS-NP, we found that the more active β-carbolines are all more lipophilic and larger than the less active compounds. Lastly, on the basis of the NCI human tumor cell line anticancer drug screen and the NCI COMPARE algorithm, it appears that some of these compounds, including 5a and 5k, seem to act as protein synthesis inhibitors.

BETA CARBOLINE DERIVATIVES USEFUL IN THE TREATMENT OF PROLIFERATIVE DISORDERS

The invention provides novel beta-carboline derivatives of formulae (la) and (lb) useful in the treatment of proliferative disorders including cancer, intermediates used in their preparation, processes for preparing the same and uses thereof.