40358-31-4Relevant articles and documents
Chalcone-inspired rA1/A2A adenosine receptor ligands: Ring closure as an alternative to a reactive substructure
Aucamp, Janine,Janse van Rensburg, Helena D.,Legoabe, Lesetja J.,Matthee, Chrisna,Terre’Blanche, Gisella
, (2021/12/30)
Over the past few years, great progress has been made in the development of high-affinity adenosine A1 and/or A2A receptor antagonists—promising agents for the potential treatment of Parkinson's disease. Unfortunately, many of these compounds raise structure-related concerns. The present study investigated the effect of ring closures on the rA1/A2A affinity of compounds containing a highly reactive α,β-unsaturated carbonyl system, hence providing insight into the potential of heterocycles to address these concerns. A total of 12 heterocyclic compounds were synthesised and evaluated in silico and in vitro. The test compounds performed well upon qualitative assessment of drug-likeness and were generally found to be free from potentially problematic fragments. Most also showed low/weak cytotoxicity. Results from radioligand binding experiments confirm that heterocycles (particularly 2-substituted 3-cyanopyridines) can replace the promiscuous α,β-unsaturated ketone functional group without compromising A1/A2A affinity. Structure–activity relationships highlighted the importance of hydrogen bonds in binding to the receptors of interest. Compounds 3c (rA1Ki?=?16?nM; rA2AKi?=?65?nM) and 8a (rA1Ki?=?102?nM; rA2AKi?=?37?nM), which both act as A1 antagonists, showed significant dual A1/A2A affinity and may, therefore, inspire further investigation into heterocycles as potentially safe and potent adenosine receptor antagonists.
Catalyst-free synthesis of 2,3-dihydro-1,5-benzothiazepines in a renewable and biodegradable reaction medium
Yadav, Neetu,Yadav, Vijay B.,Ansari, Mohd Danish,Sagir, Hozeyfa,Verma, Ankit,Siddiqui
supporting information, p. 7011 - 7014 (2019/05/17)
A clean and efficient strategy for the synthesis of benzothiazepines from chalcone and ortho-aminothiophenol has been reported. Here, glycerol, a biodegradable and reusable promoting medium, has been utilized under acid, base or metal-free conditions. The
Microwave assisted synthesis of 1,5-benzothiazepines using greener reaction medium
Kotalwar, Sanjay S.,Kale, Amol D.,Kohire, Ram B.,Jagrut, Vasant B.
, p. 993 - 996 (2019/04/05)
An efficient and eco-friendly synthesis of 1,5-benzothiazepines has been developed by the reaction of various 2-propen-1-ones with 2-aminothiophenol using microwave irradiation in greener reaction medium, glycerol. The clean reaction conditions, shorter r
Di-cationic ionic liquid catalyzed synthesis of 1,5-benzothiazepines
Sakirolla, Raghavendra,Tadiparthi, Krishnaji,Yaeghoobi, Marzieh,Rahman, Noorsaadah Abd.
, p. 107 - 115 (2017/12/26)
A simple and elegant method for the synthesis of 1,5-benzothiazepines has been developed using di-cationic liquid as a solvent cum catalyst by the reaction of o-aminothiophenol with a variety of chalcones under mild reaction conditions. Furthermore the re
A practical synthesis of 2,3-dihydro-1,5-benzothiazepines
Albanese, Domenico C. M.,Gaggero, Nicoletta,Fei, Meng
supporting information, p. 5703 - 5707 (2017/12/06)
2,3-Dihydro-1,5-benzothiazepines have been obtained through a domino process involving a Michael addition of 2-aminothiophenols to chalcones, followed by in situ cyclization. Up to 98% chemical yields have been obtained at room temperature under essential
Nanocrystalline ZSM-5 based bi-functional catalyst for two step and three step tandem reactions
Srivastava, Rajendra,Sarmah, Bhaskar,Satpati, Biswarup
, p. 25998 - 26006 (2015/10/20)
A Pd nanoparticle decorated nanocrystalline ZSM-5 catalyst was prepared for one-pot tandem reactions. The catalyst was characterized by the complementary combination of X-ray diffraction, N2-adsorption, electron microscopy, and NH3-temperature programmed desorption techniques. The catalyst was investigated in the one-pot tandem conversion of benzyl alcohol to 1,3-diphenyl-3-(phenylamino)propan-1-one, (E)-chalcone, and 2,3-dihydro-1,5-benzothiazepine. 1,3-Diphenyl-3-(phenylamino)propan-1-one and (E)-chalcone were prepared by two step tandem reactions from benzyl alcohol, whereas 2,3-dihydro-1,5-benzothiazepine was prepared by a three step tandem reaction from benzyl alcohol. A recycling study shows that no significant decrease in the catalytic activity was observed even after three recycles. To the best of our knowledge, this is the first report which deals with such a simple route to prepare 2,3-dihydro-1,5-benzothiazepines in a one-pot tandem methodology from benzyl alcohol.
Dual inhibition of the α-glucosidase and butyrylcholinesterase studied by Molecular Field Topology Analysis
Jabeen, Farukh,Oliferenko, Polina V.,Oliferenko, Alexander A.,Pillai, Girinath G.,Ansari, Farzana Latif,Hall, C. Dennis,Katritzky, Alan R.
, p. 228 - 242 (2014/05/20)
A striking dual inhibition of enzymes α-glucosidase and butyrylcholinesterase by small drug-like molecules, including 1,4-disubstituted-1,2,3-triazoles, chalcones, and benzothiazepines, was rationalized with the help of Molecular Field Topology Analysis, a 3D QSAR technique similar to CoMFA. A common pharmacophore supported the concept of a link existing between type-2 diabetes mellitus and Alzheimer's disease. These findings will be instrumental for rational design of drug candidates for both of these conditions.
Facile synthesis of 1,5-benzothiazepines in water using tetrabutylammonium tribromide
Yan, Yunhui,Yang, Xiaojuan,Wu, Liqiang
experimental part, p. 573 - 579 (2012/06/01)
A simple, environmentally benign, and efficient method was developed for the preparation of 1,5-benzothiazepines via a one-pot condensation reaction of 2-aminothiophenol with 1,3-diaryl-2-propenones using tetrabutylammonium tribromide as an efficient and versatile catalyst in water.
Ionic liquid mediated clean synthesis of some 1,5-benzothiazepines
Yadav, Ashok K.,Gupta, Manish,Kumar, Praveen
, p. 71 - 76 (2013/12/04)
An efficient and environmentally friendly procedure for the synthesis of substituted 2,3-dihydro-1,5-benzothiazepines in ionic liquid has been developed. These derivatives have been synthesized by the condensation of substituted 2-aminobenzenethiol with 1
In silico studies on 2,3-dihydro-1,5-benzothiazepines as cholinesterase inhibitors
Ansari, Farzana Latif,Kalsoom, Saima,Zaheer-Ul-Haq,Ali, Zahra,Jabeen, Farukh
, p. 2329 - 2339 (2012/11/07)
In vitro studies on cholinesterase inhibitory potential on the three sets of 2,3-dihydro-1,5-benzothiazepines have been carried out. The compounds in Set 1 were unsubstituted on ring A, while those in Sets 2 and 3 had a 2′- and 3′-hydoxy substituent, respectively, in ring A. These studies revealed that they are mixed inhibitors of both AChE and BChE as reflected from their IC50 values. It was further observed that 3′-hydroxy substituted benzothiazepines (Set 3) were found to have stronger affinity for both AChE and BChE compared with those of Sets 1 and 2. Moreover, all the compounds in Set 3 were found to be stronger BChE inhibitors than AChE. These experimental observations were rationalized by conducting in silico studies using molecular docking tool of Molecular Operating Environment (MOE) software, thereby, a good correlation was observed between IC50 values and their binding interactions within the enzyme active site. We have observed that these interactions were electrostatic and hydrophobic in nature besides hydrogen bonding. The high BChE inhibitory potential of 3′-hydroxy substituted benzothiazepines was found to be cumulative effect of hydrogen bonding and π-π interactions between the ligand and BChE. These findings may serve as a guideline for synthesizing more potent ChE inhibitors for the treatment of Alzheimer's disease and related dementias. Springer Science+Business Media, LLC 2011.
