401 research outputs found
The Aldol Addition of 1,3-Dicarbonyl Compounds to 2-Cyanobenzaldehyde in the Synthesis of Novel 3-Substituted Isoindolinones
No full textActive methylene compounds in a very effective approach to 3-substitutedisobenzofuranones through tandem aldol/lactonization reactions
No full textIn this article we describe a new accessible methodology for the synthesis of isobenzofuran-1(3H)-ones. In
this process we exploited an effective, economic, useful and environmentally benign K2CO3 catalyzed,
solvent-free one-pot tandemaldol-lactonization reaction between activemethylene compounds andmethyl
2-carboxy benzaldehyde. A particularly simple work-up and purification procedure are additional advantages
addressed to a general green chemistry approach to this important class of heterocyclic compounds
The aldol addition of readily enolizable 1,3-dicarbonyl compounds to 2-cyanobenzaldehyde in the synthesis of novel 3-substituted isoindolinones
No full textThe aldol addition of readily enolizable 1,3-dicarbonyl compounds to 2-cyanobenzaldehyde in the presence of a tertiary amine led to a series of new 3-substituted isoindolinones. Despite the instability of the related aldols, this synthesis was possible because of the intramolecular trapping of the adducts with the cyano group due to a tandem process of cyclization-rearrangement. Simple decarboxylation of some derivatives gave access to some very useful compounds
The first organocatalytic asymmetric synthesis of 3-substituted isoindolinones
No full textHerein we describe the first asymmetric organocatalytic
synthesis of 3-substituted isoindolinones in a convenient aldolcyclization-
rearrangement tandem reaction of malonates with 2-
15 cyanobenzaldehyde. Bifunctional thiourea-cinchona catalysts proved to
be particularly effective, giving the title compounds in high yields and
moderate to good enantiomeric excesses. Moreover an efficient process of
reverse crystallization led to a further enrichment up to >99% ee
The design and synthesis of novel N-heterocyclic compounds, and their evaluation of anti-cancer and anti-viral activity
No full text2010 - 2011The thesis entitled “The design and synthesis of novel N-heterocyclic compounds, and their evaluation of anti-cancer and anti-viral activity" is divided into three chapters.
The title of the thesis clearly reflects the importance of nitrogen heterocycles compounds: in fact they are extremely pivotal structural motifs responsible for eliciting various biological activities in natural products and synthetic medicines. This has attracted the medicinal chemists towards the synthesis of various compounds having nitrogen heterocycles as useful medicines to treat various diseases. It is also evident by a large number of marketed pharmaceutical products possess nitrogen heterocycles. In each chapter different heterocycle moieties belonging to β-carboline, indoles and isoindolinones nucleus respectively are presented.
In the first chapter we presented β-carboline derivatives and their anticancer activity on different cell lines. Our lead compound was harmine, which is the most representative β-carboline alkaloid endowed with antitumor properties showing high cytotoxicity both in vitro against different human tumor cell lines and in vivo. It also exhibited remarkable DNA intercalation capacity and significant Topo I inhibition activity. We designed and synthesized novel β-carbolines derivatives with the aim to evaluate their antiproliferative properties, to acquire more information about the structural requirements for the possible improvement of the cytotoxic potential and to elucidate SARs between substituent properties and antitumor activities. Most of the compounds were evaluated for Topo I inhibitory activity and compaired to harmine. Almost all compounds demonstrated interesting cytotoxic activities in particular against prostate cancer cells PC-3 with IC50 in low micromolar range. Compound X was found to be the most potent one with IC50 value of 8 µM.
In the second chapter we reported the design and synthesis of new arbidol derivatives as antiviral agents: arbidol is an indole compound launched in the Russian Federation for the prophylaxis and treatment of influenza A and B and other acute respiratory viral infections, but due to its relatively high CC50 value, a clinical application is forbidden. So in order to reduce its toxicity and improve its antiviral properties, we carried out some structural modifications at position 2, 4, 5 and 6 on indole nucleus and we evaluated their effect on in vitro, anti- influenza virus (HA), hepatitis C virus (HCV) and chikungunya virus (CHIKV) activities. Viral infections are in fact the most common illnesses experienced by people of all ages and they are also one of the major causes of morbidity and mortality in elderly people and young children throughout the world. Currently, treatments are limited and the increasing prevalence of drug-resistant pathogens highlighted the need for new anti-viral drugs with novel mechanisms of action. Biological evaluation led us to discovery of a new potent influenza virus replication inhibitor, identified in compound 15. Particularly it showed activity against all the tested viruses, both A and B type; moreover it seemed to lead to a better inhibition of some viruses in comparison to Arbidol. This compound was also found to be a promising lead compound for the design of new HCV virus replication inhibitors. Actually, biological study are in course to better study mechanism underwent the action of compound 15, which could act non only as virus replication inhibitor but also as fusion inhibitor. Then a focused analysis on the interaction of this compound with the HA protein will be carried out.
The third chapter is divided into two sections.
Section A provided a brief introduction about aldol addition to 1,3-dicarbonyl compounds and described a simple and effective multicomponent regioselective one pot aldol addition/protection reaction of β-ketoesters to a series of aldehydes in the presence of Me3SiCl and i-Pr2EtN. The analysis of the scope and application of reaction revealed a dramatic dependence of the reactivity on the used substrates.
Section B described a simple and general access to a series of new phthalimidines derivatives, (mentioned in Section A) in the presence of tertiary amines under very mild conditions exploiting the aldol addition of readily enolizable 1,3 dicarbonyl compounds to 2-cyanobenzaldehyde. Recently, it has been recognized that 3-substituted isoindolinones possess a variety of biological activity, consequently, considerable effort has been devoted to the synthesis of this nitrogen heterocycle, which also act as useful synthetic building blocks and intermediates in organic synthesis.
The obtained 3-substituted isoindolinones were preliminary tested on two different virus strains (HCV and CHIKV virus) to evaluate potential activity on the virus replication, but unfortunately it was found that all compounds were not active. However further studies are desirable focusing on activities like hypnothic, anti-schizophrenia etc, for which isoindolinone moiety also shows important applications. [edited by author]X n.s
Multi-component, regio-selective aldol addition of b-ketoesters to aldehydes: scope and applications
No full textSimple and effective multi-component one-pot aldol addition/protection reactions of b-ketoesters to a series of aldehydes in the presence Me3SiCl and i-Pr2EtN have been described. The analysis of the scope of the reaction revealed a dramatic dependence of the reactivity on the substrates used. Thus the effect of a catalytic amount of DMF and different reaction conditions was widely investigated. Further transformations of the aldol adducts were particularly useful to give valuable diols and compounds with quaternary stereocenters, while X-ray structural analysis gave also important stereochemical information about this challenging reaction
Synthesis and Cytotoxic Activity of New beta-carboline Derivatives
No full textOn the basis of harmine and 1-methoxy-canthin-6-one chemical structures, a series of novel 1,4-disubstituted and 1,4,9-trisubstituted β-carbolines and tetracyclic derivatives were designed and synthesized. Cytotoxic activities of these compounds in vitro were investigated in a human tumor cell line panel. Almost all compounds demonstrated interesting cytotoxic activities in particular against prostate cancer cells PC-3 with IC 50 in the low micromolar range. Compound X was found to be the most potent one with IC 50 value of 8.0 βM; this suggests further studies with models of prostate cancer
Design of inhibitors of influenza virus membrane fusion: Synthesis, structure-activity relationship and in vitro antiviral activity of a novel indole series
No full textThe fusion of virus and endosome membranes is an essential early stage in influenza virus infection. The low pH-induced conformational change which promotes the fusogenic activity of the haemagglutinin (HA) is thus an attractive target as an antiviral strategy. The anti-influenza drug Arbidol is representative of a class of antivirals which inhibits HA-mediated membrane fusion by increasing the acid stability of the HA. In this study two series of indole derivatives structurally related to Arbidol were designed and synthesized to further probe the foundation of its antiviral activity and develop the basis for a structure-activity relationship (SAR). Ethyl 5-(hydroxymethyl)-1-methyl-2-(phenysulphanylmethyl)-1. H-indole-3-carboxylate (15) was identified as one of the most potent inhibitors and more potent than Arbidol against certain subtypes of influenza A viruses. In particular, 15 exhibited a much greater affinity and preference for binding group 2 than group 1 HAs, and exerted a greater stabilising effect, in contrast to Arbidol. The results provide the basis for more detailed SAR studies of Arbidol binding to HA; however, the greater affinity for binding HA was not reflected in a comparable increase in antiviral activity of 15, apparently reflecting the complex nature of the antiviral activity of Arbidol and its derivative
Defensing Confidentiality During Complete Packet Inspection On A Middlebox
No full textIn Internet to encrypt traffic, HTTPS provides secure and private data communication between clients and servers. Network operators often deploy middleboxes to perform deep packet inspection DPI to detect attacks using techniques ranging from simple keyword matching to more advanced machine learning and data mining analysis. But this approach cannot protect users' private information from a service provider who deploys middleboxes. SPABox, a middlebox based system that supports both keyword based and data analysis based DPI functions over encrypted traffic. SPABox preserves privacy by using a novel protocol with a limited connection setup overhead. In this paper to further improve the performance, we are working on the network performance requirements. K. Geetharani | K. Kowsalya | A. M. SenthilKumar | M. S. Vijaykumar | M. Saravanakumar "Defensing Confidentiality During Complete Packet Inspection On A Middlebox" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-2 | Issue-3 , April 2018, URL: https://www.ijtsrd.com/papers/ijtsrd10725.pd
Secondary studies in the academic context: A systematic mapping and survey
No full textContext: Several researchers have reported their experiences in applying secondary studies (Systematic Literature Reviews — SLRs and Systematic Mappings — SMs) in Software Engineering (SE). However, there is still a lack of studies discussing the value of performing secondary studies in an academic context. Goal: The main goal of this study is to provide an overview on the use of secondary studies in an academic context. Method: Two empirical research methods were used. Initially, we conducted a SM to identify the available and relevant studies on the use of secondary studies as a research methodology for conducting SE research projects. Secondly, a survey was performed with 64 SE researchers to identify their perception related to the value of performing secondary studies to support their research projects. Results: Our results show benefits of using secondary studies in the academic context, such as providing an overview of the literature as well as identifying relevant research literature on a research area enabling to find reasons to explain why a research project should be approved for a grant and/or supporting decisions made in a research project. Difficulties faced by SE graduate students with secondary studies are that they tend to be conducted by a team and it demands more effort than a traditional review. Conclusions: Secondary studies are valuable to graduate students. They should consider conducting a secondary study for their research project due to the benefits and contributions provided to develop the overall project. However, the advice of an experienced supervisor is essential to avoid bias. In addition, the acquisition of skills can increase student's motivation to pursue their research projects and prepare them for both academic or industrial careers
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