Department Of Pharmaceutical Sciences and Natural Products

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Author: search.filters.author.Kumar, R.Has files: Yes

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    Cyclocondensation reactions of an electron deactivated 2-aminophenyl tethered imidazole with mono/1, 2-biselectrophiles: synthesis and DFT studies on the rationalisation of imidazo [1, 2-a] quinoxaline versus benzo [f] imidazo [1, 5-a][1, 3, 5] triazepine selectivity switches.
    (Royal Society of Chemistry, 2018) Joshi, G.; Chauhan, M; Kumar, R; Thakur, A; Sharma, S; Singh, R.; Wani, A.A.; Sharon, A.; Bharatam, P.V; Kumar, R.
    Microwave-promoted ring-closure reactions of 5-amino-1-(2-aminophenyl)-1H-imidazole-4-carbonitrile (7) with various mono/1,2-biselectrophiles are presented. The reaction of 7 with aldehydes, ketones and isocyanates produced the corresponding Pictet–Spengler (PS) products i.e. the imidazo[1,2-a]quinoxaline ring system via 6-endo-trig cyclisation. On the other hand, the reaction of 7 with CH(OEt)3, and CDI resulted in the formation of benzo[f]imidazo[1,5-a][1,3,5]triazepine scaffolds via a 7-exo-trig cyclisation process. The mechanistic aspects of these ring cyclisation processes have been analysed and studied to rationalise 6- versus 7-membered ring formation using density functional theory (DFT). DFT calculations revealed the involvement of N-Heterocyclic Carbene (NHC) in the PS reaction mechanism.
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    Unanticipated Cleavage of 2-Nitrophenyl-Substituted N-Formyl Pyrazolines under Bechamp Conditions: Unveiling the Synthesis of 2-Aryl Quinolines and Their Mechanistic Exploration via DFT Studies.
    (ACS Publications, 2018) Joshi, G; Wani, A.A.; Sharma, S; Bhutani, P; Bharatam, P.V.; Paul, A.T.; Kumar, R.
    We herein report for the first time an unusual decomposition of 2-nitrophenyl-substituted N-formyl pyrazolines under Bechamp reduction condition employed to yield 2-aryl quinolines exclusively instead of pyrazolo[1,5-c]quinazolines. The reaction investigation suggests acid-mediated cleavage of 1 followed by a retro-Michael addition, and a subsequent in situ intramolecular reductive cyclization through a modified Friedlander mechanism afforded 2-aryl quinolines (2) in good yields. The proposed mechanistic pathways were supported via experimental evidence and density functional theory studies. B3LYP/6-31+G(d) analysis indicated the involvement of trans-2-hydroxyaminochalcone as a key intermediate and its isomerization and cyclization, leading to unusual product formation.
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    Understanding the multifaceted role of ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) and its altered behaviour in human diseases
    (Bentham Science Publishers B.V., 2015) Cholia, R.P.; Nayyar, H.; Kumar, R.; Mantha, Anil K.
    Ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2) also known as Autotaxin, is a secreted lysophospholipase D, which hydrolyzes lysophosphatidylcholine (LPC) into Lysophosphatidic acid (LPA). LPA is the bioactive product of ENPP2 enzyme, which induces diverse signalling pathways via six LPA-G-protein coupled receptors (GPCRs). ENPP2 is an essential protein for normal development and its altered expression is associated with various human diseases. Cellular ENPP2 silencing results in lethality at the embryonic stage in mice. Initially, it is identified as an autocrine factor in melanoma cells. Different research groups are currently exploring to understand the multifaceted role of ENPP2 in various processes such as embryonic and neural development, migration, invasion, differentiation, proliferation, angiogenesis, and survival. Altered expression of ENPP2 is also associated with various diseases like inflammation, cancer, fibrosis, rheumatoid arthritis and neural defects. In this article, we have summarized structural aspects of ENPP2 and biochemical functions associated with its diverse cellular roles in various human diseases including cancer and Alzheimer's disease (AD). In addition, keeping in view and advocating findings, a note on various phytochemicals and synthetic inhibitors, which are currently explored as therapeutic agents targeting functions of ENPP2 for the treatment of various human diseases is also presented. ? 2015 Bentham Science Publishers.