2898-08-0Relevant articles and documents
Synthesis and biological evaluation of benzodiazepines containing a pentafluorosulfanyl group
Jose, Arathy,Tareque, Raysa Khan,Mortensen, Martin,Legay, Remi,Coles, Simon J.,Tizzard, Graham J.,Greenland, Barnaby W.,Smart, Trevor G.,Bagley, Mark C.,Spencer, John
, (2021)
The widely used pentafluorosulfanyl group (SF5) was deployed as a bioisosteric replacement for a chloro-group in the benzodiazepine diazepam (Valium). Reaction of 2-amino-5-pentafluorosulfanyl-benzophenone with chloroacetyl chloride followed by hexamethylenetetramine, in the presence of ammonia, led to 7-sulfurpentafluoro-5-phenyl-1H-benzo[1,4]diazepin-2(3H)-one (2c). The latter was able to undergo a Pd-catalysed ortho-arylation, demonstrating that these highly fluorinated benzodiazepines can be further modified to form more complicated scaffolds. The replacement of Cl by the SF5 group, led to a loss of potency for potentiating GABAA receptor activation, most likely because of a lost ligand interaction with His102 in the GABAA receptor α subunit. Dedicated to Professor Jonathan Williams, an inspirational and humble pioneer, a colleague and mentor in chemistry.
Structure-Activity Relationship Studies of Retro-1 Analogues against Shiga Toxin
Abdelkafi, Hajer,Michau, Aurélien,Pons, Valérie,Ngadjeua, Flora,Clerget, Alexandra,Ait Ouarab, Lilia,Buisson, David-Alexandre,Montoir, David,Caramelle, Lucie,Gillet, Daniel,Barbier, Julien,Cintrat, Jean-Christophe
, p. 8114 - 8133 (2020/09/21)
High-throughput screening has shown that Retro-1 inhibits ricin and Shiga toxins by diminishing their intracellular trafficking via the retrograde route, from early endosomes to the Golgi apparatus. To improve the activity of Retro-1, a structure-activity relationship (SAR) study was undertaken and yielded an analogue with a roughly 70-fold better half-maximal effective concentration (EC50) against Shiga toxin cytotoxicity measured in a cell protein synthesis assay.
Molecular docking, synthesis and CNS activity of some novel 1, 4-Benzodiazepine derivatives
Menghani, Sunil S.,Chikhale, Rupesh,Pant, Amit,Mathew, Bijo,Khedekar, Pramod
, p. 690 - 698 (2017/07/15)
Background: A series of new class of twenty four 1, 4-benzodizepines were designed and by using molecular docking study with GABAA receptor, high scoring fourteen molecules were synthesized from this library. Binding affinity of ligands towards GABAA was evaluated on the basis of dock score and bonding interactions like hydrogen bonds, hydrophobic bonds and pi-stacking. Methods: All compounds were found to possess a good dock score, but varied in the formation of bonding interactions. Methoxy group substituted ligands showed particularly very important role in these interactions. All the synthesized molecules were characterized by IR, 1H-NMR and Mass spectrometric data and investigated for their antianxiety and antiepileptic actions. Conclusion: Compound 3-(3-ethoxy-4-hydroxybenzylidene)-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one was found to possess very effective in both the activities. All results, docking as well as pharmacological evaluations were compared to diazepam.