2244-60-2Relevant academic research and scientific papers
Tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives can specifically target bacterial DNA ligases and can distinguish them from human DNA ligase I
Yadav, Nisha,Khanam, Taran,Shukla, Ankita,Rai, Niyati,Hajela, Kanchan,Ramachandran, Ravishankar
, p. 5475 - 5487 (2015)
DNA ligases are critical components for DNA metabolism in all organisms. NAD+-dependent DNA ligases (LigA) found exclusively in bacteria and certain entomopoxviruses are drawing increasing attention as therapeutic targets as they differ in their cofactor requirement from ATP-dependent eukaryotic homologs. Due to the similarities in the cofactor binding sites of the two classes of DNA ligases, it is necessary to find determinants that can distinguish between them for the exploitation of LigA as an anti-bacterial target. In the present endeavour, we have synthesized and evaluated a series of tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives for their ability to distinguish between bacterial and human DNA ligases. The in vivo inhibition assays that employed LigA deficient E. coli GR501 and S. typhimurium LT2 bacterial strains, rescued by ATP-dependent T4 DNA ligase or Mycobacterium tuberculosis NAD+-dependent DNA ligase (Mtb LigA), respectively, showed that the compounds can specifically inhibit bacterial LigA. The in vitro enzyme inhibition assays using purified MtbLigA, human DNA ligase I & T4 DNA ligase showed specific inhibition of MtbLigA at low micromolar range. Our results demonstrate that tricyclic dihydrobenzoxazepine and tetracyclic indole derivatives can distinguish between bacterial and human DNA ligases by ～5-folds. In silico docking and enzyme inhibition assays identified that the compounds bind to the cofactor binding site and compete with the cofactor. Ethidium bromide displacement and gel-shift assays showed that the inhibitors do not exhibit any unwanted general interactions with the substrate DNA. These results set the stage for the detailed exploration of this compound class for development as antibacterials.
Methods for Treating Cognitive Disorders Using Inhibitors of Histone Deacetylase
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Paragraph 0634, (2017/01/23)
This disclosure relates to compounds for the inhibition of histone deacetylase and treatment of a cognitive disorder or deficit. More particularly, the disclosure provides for compounds of formula (I) wherein Q, J, L and Z are as defined in the specification.
Towards a general ruthenium-catalyzed hydrogenation of secondary and tertiary amides to amines
Cabrero-Antonino, Jose R.,Alberico, Elisabetta,Junge, Kathrin,Junge, Henrik,Beller, Matthias
, p. 3432 - 3442 (2016/05/19)
A broad range of secondary and tertiary amides has been hydrogenated to the corresponding amines under mild conditions using an in situ catalyst generated by combining [Ru(acac)3], 1,1,1-tris(diphenylphosphinomethyl)ethane (Triphos) and Yb(OTf)3. The presence of the metal triflate allows to mitigate reaction conditions compared to previous reports thus improving yields and selectivities in the desired amines. The excellent isolated yields of two scale-up experiments corroborate the feasibility of the reaction protocol. Control experiments indicate that, after the initial reduction of the amide carbonyl group, the reaction proceeds through the reductive amination of the alcohol with the amine arising from collapse of the intermediate hemiaminal.
N-substituted azaheterocyclic carboxylic acids and alkylesters thereof
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, (2008/06/13)
The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.
Heterocyclic compounds
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, (2008/06/13)
The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.
1-,2-,3-,4-,5-,6-,7-,8- AND/OR 9 SUBSTITUTED DIBENZOXAZEPINE COMPOUDS, PHARMACEUTICAL COMPOSITIONS AND METHODS FOR TREATING PAIN
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, (2008/06/13)
The present invention provides substituted dibenzoxazepine compounds of Formula I: STR1 which are useful as analgesic agents for the treatment of pain, pharmaceutical compositions comprising a therapeutically-effective amount of a compound of Formula I in combination with a pharmaceutically-acceptable carrier, and a method for eliminating or ameliorating pain in an animal comprising administering a therapeutically-effective amount of a compound of Formula I to the animal.
3-alkoxy-2-aminopropyl heterocyclic amines and their use as cardiovascular agents
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, (2008/06/13)
Propylamines of the formula (I): STR1 and isomers thereof, particularly those enantiomers and racemates relative to the chiral carbon indicated by an asterisk (*). The propylamines can be used for the treatment of hypertension or angina in humans. A is pyrrolidine, piperidine or morpholine, Z is alkylene, alkenylene, oxygen or a sulfur atom and W is an oxygen or a sulfur atom.
