benzimidazoles derivatives / GSK - LARVOL DELTA

"Congratulations to Yong Lee from @GSK on winning the Best Talk Prize at the National Undergraduate Industrial Placement Showcase 2023 - at The University of Manchester on the 21th May. Titled: Bayesian optimisation approach for process optimisation of benzimidazole derivative" (@SCIYoungChem)

Divergent synthesis of unsymmetrical annulated biheterocyclic compound libraries: Benzimidazole Linked Indolo-benzodiazepines/quinoxaline (ACS) - A reagent based diversification approach coupled with the Pictet-Spengler-type condensation was used to construct the tetracyclic indolo-benzodiazepines/quinoxalines on substituted benzimidazoles;

Oncology

Functionalized Benzimidazole Scaffolds: Privileged Heterocycle for Drug Design in Therapeutic Medicine. (PubMed) - Arch Pharm (Weinheim) - "This manuscript deals with the recent advances in the synthesis of benzimidazole derivatives, the widespread biological activities as well as pharmacokinetic reports. These present them as a toolbox for fighting infectious diseases and also make them excellent candidates for future drug design."

Journal • Biosimilar • Gene Therapies

SYNTHESIS AND IN VITRO ANTIPROLIFERATIVE ACTIVITY OF NOVEL 2-ARYLIDENEAMINOBENZIMIDAZOLE DERIVATIVES. (PubMed) - Acta Pol Pharm - "The most active compound against the cancer cell lines was 4-amino-3-cyano-2-(4-hydroxyphenylene)-1,2-dihydropyrimi-do[1,2-a]benzimidazole (29) (IC50 0.23 ± 0.05 µg/mL against MV4-11 cells) showing in parallel very low cytotoxicity towards mouse fibroblasts. Cisplatin was the control drug."

Journal • Biosimilar • Leukemia • Oncology • Triple Negative Breast Cancer

Cytotoxic, Antiproliferative and Apoptotic Effects of New Benzimidazole Derivatives on A549 Lung Carcinoma and C6 Glioma Cell Lines. (PubMed) - "Anticancer activity of the compounds was evaluated using MTT assay, BrdU assay and flow cytometric analysis on A549 human lung carcinoma and C6 rat glioma cell lines. Compounds bearing dimethylamino moiety exhibited higher antitumor activity."

Journal • Biosimilar • Oncology

Exploration of 2-benzylbenzimidazole scaffold as novel inhibitor of NF-κB. (PubMed) - Bioorg Med Chem - "Although most of the benzimidazole derivatives showed strong inhibitory activity in low micromolar potency, 2-(4-methoxybenzyl)-1H-benzo[d]imidazole (3m; IC50=1.7μM) and 2-(2-methoxybenzyl)-1H-benzo[d]imidazole (3n; IC50=2.4μM) showed the best inhibition. The structure activity relationship revealed that 2-benzylbenzimidazole scaffold with hydrogen bonding acceptor on phenyl ring appears as a pharmacophore."

Journal • Biosimilar

Anti-inflammatory trends of new benzimidazole derivatives. (PubMed) - Future Med Chem - "A strong inhibition of secretory phospholipases A2 was exhibited by benzimidazole derivatives with trifluoromethyl and methoxy substitutions at position 4 of attached phenyl, whereas compound 8 containing pyridine ring substituted with amino group showed very potent 5-lipoxygenase inhibition. Molecular docking experiments were carried out to elucidate the molecular basis of the observed inhibitory activities."

Journal • Biosimilar • Immunology

Phenolic Metabolites of Dalea ornata Affect Both Survival and Motility of the Human Pathogenic Hookworm Ancylostoma ceylanicum. (PubMed) - J Nat Prod - "The rotenoids deguelin (9) and tephrosin (10), predictably perhaps, were the most active, with complete worm mortality observed by day 4 (or earlier) at 6.3 and 6.0 μM, respectively. The effects of 1-10 on hookworm motility and on toxicity to hamster splenocytes were also explored as important measures of treatment potential."

Journal • Biosimilar

Discovery, Optimization, and in vivo Evaluation of Benzimidazole Derivatives AM-8508 and AM-9635 as Potent and Selective PI3K Inhibitors. (PubMed) - J Med Chem - "These compounds which share a benzimidazole bicycle are effective when ad-ministered in vivo at unbound concentrations consistent with their in vitro cell potency as a consequence of improved unbound drug concentration with lower unbound clearance. Furthermore, the compounds demonstrated efficacy in a Keyhole Limpet Hemocyanin (KLH) study in rats, where the blockade of PI3Kactivity by inbibitors 1 and 2 led to effective inhibition of antigen-specific IgG and IgM for-mation after immunization with KLH."

Journal • Biosimilar

Recent Development of Benzimidazole-Containing Antibacterial Agents. (PubMed) - ChemMedChem - "In this minireview we summarize novel benzimidazole derivatives active against various bacterial strains. In particular, we outline the relationship between the structures of variously modified benzimidazoles and their antibacterial activity."

Journal • Review • Biosimilar

Tautomeric and non-tautomeric N-substituted 2-iminobenzimidazolines as new lead compounds for the design of anti-influenza drugs: An in vitro study. (PubMed) - Bioorg Med Chem - "It was found that some of synthesized benzimidazole derivatives (7 of 22, 32%) possess strong virus-inhibiting activity against pandemic influenza virus (IC50's in low micromolar range) with quite moderate cytotoxicity (CC50 in the range of thousands micromoles). Due to their high selectivity (highest SI's=50-83) these compounds are of significant interest for further in vivo experiments as well as for further structural optimization and drug development."

Journal • Biosimilar