International Conference on Pharmaceutical Chemistry September 05-07, 2016 Frankfurt, Germany

Biography:

Bhimapaka China Raju completed his PhD from Osmania University and Post-doctoral studies from Prof. H C Brown Center for Borane Research, Purdue University, USA. He is the Senior Scientist of CSIR-IICT, India a premier scientific organization. He has published 66 papers in reputed journals and has been serving as an Editorial Board Member of Oriental Journal of Chemistry, International Journal of Chemistry & Applications and E-Journal of Chemistry.

Abstract:

Heterocyclic compounds and their derivatives are important and are present in many biological systems. Among them, pyridine derivatives have found several applications in the pharmaceutical and agrochemical fields. Extensive studies have been carried out on synthesis of pyridine compounds because of their importance as drugs and natural products. Chloronicotinaldehydes are good precursors for the annulation of variety of heterocyclic analogues. Imidacloprid is the first chloronicotinyl insecticide, used worldwide for controlling pests due to its potency, broad spectrum of insecticidal activity with low mammalian toxicity. Our research group focused on 2-chloronicotinaldehyde based heterocyclic compounds, namely, Imidacloprid analogues, 2-chloro-5-methylpyridine-3-olefin derivatives, 1,8-naphthyridines, Baylis-Hillman (BH) adducts, 1H-1,2,3-triazolylbenzohydrazides, Knoevenagel derivatives, (E) α,β-unsaturated esters, ketones and studied their anti-microbial, anti-mycobacterial and anti-cancer activities. Further, we prepared various 1H-1,2,3-triazoles, 1H-1,2,3-triazolylisoxazoles and 1H-1,2,3-triazolyldihydroisoxazoles starting from 2-chloronicotinaldehydes in combination with TMP and screened for their anti-cancer and anti-tubulin properties. 

Biography:

Mrinalkanti Kundu is a Medicinal Chemist and carries 13 years of experience in small molecule therapeutics via orthosteric/allosteric modulation of GPCR, ion channels and enzymes with a track record in delivering pre-clinical candidates for metabolic disorders, pain, oncology and anti-infective programs. He completed his MSc and PhD from Indian Institute of Technology in Bioorganic Chemistry and was awarded Post-doctoral Fellowships in the field of Chemical Biology from University of Uppsala, National Institute on Aging, in collaboration with The Johns Hopkins University and University of Basel and published 10 patents, 15 articles and 1 book chapter.

Abstract:

DNA has played a key role as a molecular target for many of the drugs that have been used for decades in cancer therapeutics. Compounds that target DNA are some of the most effective agents in clinical use and produced increase in cancer patients’ survival but, they are extremely toxic. Consequently, enormous effort has been put into finding more selective agents; thus, there is considerable excitement in identifying cancer-specific DNA targets and thereby resulting in less toxic new therapeutics. This has driven interest in targeting unusual, non-canonical structures of DNA, in order to achieve selectivity while potentially reducing adverse side effects. Accordingly, cell-permeable specific probes targeting G-quadruplex structures should provide researchers with new tools for studying their potential involvement in gene expression, chromosome stability, viral integration and recombination. Significant research is in progress targeting G-quadruplex DNA with small molecules hoping to inhibit cancer growth according to two distinct mechanisms; first, promoter deactivation and second, inhibition of telomerase which is responsible for maintaining length of telomeres, and is involved in around 85% of all cancers. We wish to report the design, synthesis of novel drug-like small molecules and their biological evaluation as potential G-quadruplex stabilizing agents. Efficiency of these synthetic compounds for the stabilization of promoter quadruplex DNA structures was performed along with thorough investigation to assess the quadruplex binding affinity by using various biophysical and biochemical studies. For some of the compounds, the binding mode was explained by molecular modelling studies and their potential anti-cancer inhibitory effect was also tested.

Biography:

Chunduri Venkata Rao is currently a Professor of Chemistry in Sri Venkateswara University Tirupati. His area of research interest is Natural Products Chemistry and Synthesis of bioactive heterocyclic compounds. He has supervised 18 students for PhD and 6 for MPhil. At present 6 Research Scholars are working for their PhD Program. He has published over 70 research papers in national and international peer reviewed journals. He is a life member of ICC, Agra. He is serving as a reviewer and Editorial Board Member of reputed journals. In recent years he focused on the synthesis of various biologically active thieno & seleno pyrimidine derivatives.

Abstract:

Pyrimidines and fused pyrimidines are important classes of heterocyclic compounds that exhibit a broad spectrum of biological activities such as anticancer, antiviral, antibacterial, antioxidant, anti-inflammatory and analgesic activities. Among them quinazoline is the important scaffold which is an existing core moiety in gefitinib (as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer), lapatinib (as breast cancer treatment). Furthermore bioisosteric replacement of benzene ring in quinazoline by thiophene ring has been an important drug design strategy to optimize various lead structures like thienopyrimidines which shows the outstanding biological activities like Hsp90 ATPase Inhibitory, Tk Inhibitors DHFR inhibitory, CDK4 inhibitory, anti-inflammatory, anticancer and antitubercular activities. These thienopyrimidine  scaffolds also widely used in the drug discovery and have been employed broadly in the design of various kinase inhibitors, including cyclin-dependent kinase, phosphoinositide 3-kinase α(PI3Kα), EGFR/ErbB-2, aurora kinase and also implicated in the potential treatment or prevention of Alzheimer’s disease. Some substituted thieno [2,3-d] pyrimidines also act as a partial agonist for the luteinizing hormone/ choriogonadotropin receptor (LHCGR) and the closely related thyroid-stimulating hormone receptor (TSHR), the above literature survey and enormous importance of thienopyrimidines in present medicinal chemistry encouraged us to select the thienopyrimidine as our basic core moiety.  Hence in the present study a series of thienopyrimidine derivatives have been selected for the synthesis by incorporating the simple pharmacophores like oxadiazole, triazole, triazolothiadiazole, Schiff and Mannich bases and studied for their biological assay for in vitro microbial and cytotoxicity activity studies. All the compounds are well characterized by spectral data.

Biography:

Paulo Roberto Ribeiro Costa obtained his Post-doctoral studies at Université Joseph-Fourier (1984) and Université Paris-Sud (1988). He is Full Professor of Organic Chemistry at the Federal University of Rio de Janeiro since 1996 and has published more than 110 papers in reputed journals. He collaborated with several laboratories of the biological area in projects aiming the discovery of new bioactive compounds, especially isoflavonoid analogues with antiviral, antiparasitic and antineoplasic properties.

Abstract:

Isoflavanoids have being used in our laboratory as inspiration for the preparation of new compounds with antiviral, antiparasitic and antineoplastic activities. Several new 1-carbaisoflavanones, designed as analogues of bioactive natural isoflavanones, were prepared in environmentally appropriate conditions, by palladium catalyzed a-arylation of a-tetralones with o-bromoalkoxyphenols. Compound LQB-314 exhibited the best profile for HCV inhibition, being active in both replicon reporter cells (IC₅₀ 1.8 mM, SI > 111 in Huh7/Rep-Feo1b and IC₅₀ 4.3 mM, SI> 46 in Huh7.5-FGR-JC1-Rluc2A). Compound LQB-307 was the more potent and selective in Huh7.5-FGR-JC1-Rluc2A replicon reporter cells (IC₅₀ 1.5 mM, SI>101.4). Both compounds presented high bioselective index. Several of these substances have been converted in high yields into the corresponding 5-carbapterocarpens (total or partial demethylation of methoxy groups, followed by cyclization in a single step). These pterocarpens also showed potent anti-HCV activity. The best profile in Huh7/Rep-Feo1b replicon reporter cells was observed with LQB-359 (EC₅₀ 5.5 mM/SI 20), while LQB-418 was the most active in Huh7.5-FGR-JC1-Rluc2A replicon reporter cells (EC₅₀ 1.5 mM/SI 70). Hydroxy groups at A- and D-rings are essential for anti-HCV activity, and substitutions in the A-ring at positions 3 and 4 resulted in enhanced activity of the compounds.

Biography:

Sameer Agarwal has obtained Master’s in Chemistry from IIT, Delhi and was awarded DAAD (German Govt. Scholarship) fellowship to purse research project at Karlsruhe University, Germany. He has received PhD degree from Technical University, Dresden, Germany in the field of Synthetic and bio-organic chemistry under direction of Prof. Dr. Hans-Joachim Knölker, FRSC, a well-known scientist of present times for his contribution towards Alkaloid Chemistry. He worked as Research Scientist (Post-Doc), JADO Technologies, (collaboration with Max Planck Institute (MPI) of Molecular Cell Biology and Genetics and Chemsitry Department, Technical University), Germany. He then decided to return to his home country and working with Zydus Research Centre, Cadila Healthcare Ltd., Ahmedabad as Principal Scientist / Group Leader in the area of basic drug discovery and his research interest includes discovery of cardio metabolic, anti-inflammatory and oncology drugs. He has large number of publications in international journals and patents and is a reviewer of many prestigious journals including American Chemical Society. 

Abstract:

TGR5 is a G protein-coupled receptor (GPCR), activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. In our pursuit of novel drugs with distinct mechanism of action for type 2 diabetes we report here the discovery of 2-((2-(4-(1H-imidazol-1-yl) phenoxy) ethyl)thio)-5-(2-(3,4-dimethoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole as a novel, potent, selective and orally bioavailable TGR5 agonist. Using computer aided modeling studies we designed a series of novel 2-thio-imidazole derivatives, and then experimentally established a structure-activity relationship (SAR). The mentioned compound was identified as a TGR5 agonist with EC50 of 57pM and 62pM against the human TGR5 and mouse TGR5 receptors, respectively, in recombinant CRE-directed luciferase reporter gene assays. The compound showed a favorable pharmacokinetic profile. Further, this compound showed in vivo GLP-1 secretion in a C57 mouse model, and it potently reduced glucose excursion in oral glucose tolerance test (OGTT) in DIO C57 mice (ED50 = 7.9 mg/kg; ED90 = 29.2 mg/kg). 

Biography:

A novel series of 1-{[3-(furan-2-yl)-5-substituted phenyl-4,5-dihydro-1,2-oxazol-4-yl]methyl}-4-methyl piperazine, compounds 3a–l have been synthesized. The synthetic work was carried out beginning from 2-acetylfuran through Claisen Schmidt condensation with different types of aromatic aldehyde, affording 1-(furan-2-yl)-3-substituted phenyl prop-2-en-1-ones which on cyclization with hydroxylamine hydrochloride resulted in 3-(furan-2-yl)-5-substitutedphenyl-4,5-dihydro-1,2-oxazole formation. The isoxazolines were subjected to Mannich’s reaction in the presence of N-methyl piperazine to produce the desired products. The chemical structures of the compounds were proved by IR, ¹HNMR, ¹³CNMR and Mass spectrometric data. The antidepressant activity of the compounds was investigated by Porsolt’s behavioral despair (forced swimming) test on Albino mice. Moreover, the antianxiety activity of the newly synthesized compounds was investigated by the plus maze method. Compounds 3a and 3k showed the duration of immobility times of 152.00(s) and 152.33(s) respectively at 10 mg/kg dose level when compared to the standard drug imipramine (149.67s). Compounds 3a and 3k also showed significant antianxiety activity. A computational study for the prediction of ADME properties of the compounds was performed. It was encouraging to note that none of the compounds violated any Lipinski’s parameter. Lipophilicity data also suggested that compounds are lipophilic enough to cross blood brain barrier. The molecular modelling studies also predicted good binding interactions of most active molecules with MAO-A. 

Abstract:

Gita Chawla graduated in Pharmacy from College of Pharmacy, University of Delhi in 1987. Then, she did her MPharm in 1989 from Hamdard College of Pharmacy, University of Delhi and PhD in 1995 from Jamia Hamdard, New Delhi, India. She is Associate Professor in the Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard, New Delhi, India. Her field of specialization includes Medicinal Chemistry/Pharmaceutical Chemistry and Synthetic Chemistry. She has a teaching and research experience of around 21 years during which many students completed their MPharm research work under her guidance and submitted their MPharm theses and has guided PhD scholars also. She has authored numerous research publications in various journals of national and international repute. She has been serving as an Editorial Board Member in international journals of repute

Biography:

Poonam Piplani completed her PhD in the year 1997 and is currently holding the post of a Professor in the Institute. She has a teaching and research experience of over 24 years. She has 35 publications in the journals of both national and international repute and has attended various national and international conferences. She has two major research projects sanctioned by the University Grants Commission and Council of Scientific and Industrial Research, New Delhi. The Commonwealth Scholarship Commission, United Kingdom had selected her for the Commonwealth Academic Staff Fellowship, at the University of Starthclyde, Glasgow, UK. She has been included in the panel of PCI inspectors by the Pharmacy Council of India.

Abstract:

These days, dementia is a very costly burden on public health and an unmet medical need. Till date, many molecular targets such as acetylcholinesterase, phosphodiesterase, dopamine receptors, NMDA receptors, acetylcholine receptors etc. and behavioural pharmacological models have been studied for the discovery of new potential cognition enhancers. However, targeting inhibition of acetylcholinesterase has produced many clinically used block buster drugs. Piperazine is considered as a privileged structure as substitution at various positions of this nucleus results in a variety of derivatives possessing diversified biological properties. The functional importance of piperazine derivatives in cognition imposes very high requirements on their development as drug candidates. It was thus envisioned to synthesize some newer compounds having a better therapeutic profile by incorporating N₄ substituted piperazine ring and a substituted aryloxy moiety linked through various spacers in a single molecule. They will probably have the ability to interact with both the catalytic and the peripheral site of AChE, anticipating, the molecules may act as dual binding site AChE inhibitors. These compounds should be able to decrease the cognitive dysfunction and increase the cholinergic neurotransmission. Combining the chemical and pharmacological point of view, a series of novel piperazine derivatives has been designed, synthesized and evaluated for cognition improvement. All the synthesized compounds were evaluated as dual binding site inhibitors of acetylcholinesterase. The compounds encompassed an aryloxy moiety, a substituted piperazine and either a C-2 or C-3 spacer, so that they could interact with both the catalytic site and the peripheral anionic site (PAS) of acetylcholinesterase enzyme. The SAR study revealed that N-(4-{3-[4-(4-fluoro-phenyl)-piperazin-1-yl]-propoxy}-phenyl)-acetamide (I) containing the 4-(N-acetylamino)phenoxy and N₄-(p-fluorophenyl) piperazinyl moieties with a C-3 spacer was found to be the most active with IC₅₀ value 0.49 μM. Docking study showed that the carbonyl O-atom was involved in H-bonding with TYR130 and both the aromatic rings showed π-π stacking contact with Phe330, TRP84 and TRP279. In addition, the compound showed dual binding site inhibition and mixed type inhibition characteristics from enzyme kinetics studies. Furthermore, ex-vivo study exhibited CNS penetration ability, and was found to be active in passive avoidance memory evaluator model at a dose level of 1mg/kg. It also showed significant antiradical activity. Therefore, these evidences suggested that (I) could be developed as a prospective neuroprotectant and a cognition enhancer for the future pursuit. 

Biography:

Asunción Barbero studied Chemistry at the University of Valladolid and received her PhD degree at the same university working with Prof. Pulido. She then held Postdoctoral Fellowships at the University of Cambridge for two years working under the supervision of Prof. Ian Fleming in the study of stereocontrol in organic synthesis using silicon chemistry. She came back to Valladolid as Assistant Professor, was promoted to Associate Professor in 2001 and obtained the Spanish habilitation to full Professor in 2012. She has co-authored numerous international scientific publications and has delivered several invited and plenary lectures. Her current interests include the study of the silyl-cupration of multiple bonds and its application to the synthesis of natural and related products.

Abstract:

Biography:

Settypalli Triloknadh is currently doing PhD as UGC-SRF fellow under the supervision of Prof. C Venkata Rao in the Department of Chemistry, Sri Venkateswara University Tirupati, Andhra Pradesh, India. He has qualified national level Joint CSIR-UGC-JRF & NET exam under JRF category held in June-2011. He has attended several National & International conferences. He has been awarded the Prof. G L Talesara award-2014 for the Best Oral Presentation of his paper in Organic Chemistry Section in the 33^rd Annual National Conference of Indian Council of Chemists held at Department of Applied Chemistry, Indian School of Mines, Dhanbad during 15^th-17^th December, 2014. He has three years of research experience in organic synthesis towards the synthesis of heterocyclic compounds.

Abstract:

Thienopyrimidines occupy a special position among fused pyrimidines compounds these derivatives are characterized by a very broad spectrum of biological activities, such as antimicrobial, antiviral, anticancer, anti-inflammatory, antihistaminic, antipyretics, anticonvulsant, and immunostimulant properties. Along with some other pyrimidine systems containing an annulated five membered hetero aromatic ring, thienopyrimidines are structural analogs of biogenic purines and can be considered as potential nucleic acid antimetabolites. Various thienopyrimidine analogues attracted additional attention due to the broad spectrum of biological properties, they exhibited with a variety of annulations and functional group manipulations possible, some thieno[2,3-d]pyrimidine derivatives have shown interesting biological activity including as Hsp90 ATPase inhibitory, Tk inhibitors, DHFR inhibitory, CDK4 inhibitory activities. Furthermore various 1,2,4-triazole and their fused heterocyclic derivatives are also shows important biological properties like antimigraine, antiviral and analgesic activities. In addition fused heterocycle of1,2,4-triazole i.e., 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole also shows wide spectrum of biological activities including anti-fungal, antibacterial, antiviral, anthelmintic, antitumor, analgesic and anti-inflammatory activities. In view of their biological significance and in continuation of our ongoing research work to find out bioactive thienopyrimidines, the present work is an effort towards the synthesis and biological evaluation of some new 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole tagged thieno[2,3-d]pyrimidine derivatives. All the synthesized compounds are characterized by the spectral analysis. Docking and anti microbial activities of the synthesized are also studied.

Biography:

Sundaram Singh has completed her PhD from BHU, Varanasi. She is the Associate Professor of Chemistry Dept., IIT (BHU), Varanasi. She has published more than 20 papers in reputed journals. Her research area is green synthesis, organic synthesis and evaluation of biological activity. 

Abstract:

Multi-component reactions (MCRs), in which multiple reactions are combined into one synthetic operation, have been used extensively to form carbon-carbon bonds in synthetic chemistry. Such reactions offer a wide range of possibilities for the efficient construction of highly complex molecules in a single procedural step, avoid the complicated purification operations and allow savings of both solvents and reagents. In the past decade, there have been tremendous development in three- and four-component reactions and great efforts continue to be made to develop new MCRs. To date the development of new MCRs is an evolving and exciting research topic in organic synthesis, particularly in the synthesis of heterocyclic compounds. Superoxide chemistry is one of the most fascinating problems of current research. The use of this novel, innocuous and biochemical species has been demonstrated for achieving a number of organic transformations. Despite some progress made in the understating of the organic chemistry of superoxide ion, an important aspect involving the use of superoxide ion in multi-component synthesis still remains untouched and warrants study in this direction. The present report demonstrates a fast and selective multi-component transformation of an amines, cyclic 1, 3-diketone and aldehydes into benzothiazolo-/benzimidazolo-quinazolinone derivatives under mild reaction conditions of superoxide ion at room temperature in excellent yields. 

Biography:

Matthias D’Hooghe received a PhD degree in 2006 from Ghent University (Belgium) for his thesis entitled “2-(Bromomethyl)aziridines as versatile building blocks in organic chemistry”. In 2007, he became Post-doctoral Assistant at Ghent University, and in 2009 he performed a Post-doctoral stay at Eindhoven University of Technology (The Netherlands). In 2010, he was promoted to Research Professor at Ghent University, and was granted tenure in 2015. His main research interests include the chemistry of small-ring azaheterocycles and the synthesis of bioactive heterocyclic compounds. He received several awards and is the author of 117 publications in international peer-reviewed journals.

Abstract:

Small-ring azaheterocyclic systems have acquired a pivotal position as building blocks in medicinal chemistry. In particular, aziridines, azetidines and beta-lactams have been shown to be eligible synthons for the construction of a broad variety of stereodefined heterocyclic frameworks, often endowed with pronounced biological activities. In this presentation, the synthetic flexibility of these three- and four-membered systems toward the preparation of different types of pharmaceutically relevant nitrogen-containing target structures will be explained. In that respect, a number of novel synthetic strategies toward a broad set of important heterocyclic scaffolds will be discussed (see figure below). In particular, different new methods for the regio- and stereoselective rearrangement of aziridines, azetidines and beta-lactams into functionalized four- to seven-membered hetero (bi)cycles will be disclosed. All these compounds represent relevant moieties encountered as substructures in a variety of biologically active natural products and pharmaceuticals.

Biography:

Vânia André has completed his PhD from University of Lisbon and currently a Post-doctoral fellow at Universities of Lisbon and Aveiro. She has published more than 50 papers in reputed international journals, 2 patents, 5 book chapters, 3 national publications and over 80 communications. She attended over 20 international schools/workshops/conferences to enrich her scientific knowledge and build a network of international scientists. Since 2006, she is focused on applying Crystal Engineering and Supramolecular Chemistry towards improving crystal forms of active pharmaceutical ingredients. Currently she is developing bio-inspired metal organic frameworks for enhanced drug storage, delivery and release. 

Abstract:

Nanoporours materials have attracted the interest of both academia and industry in various applications, the best known being gas storage, gas separation and shape/size selective catalysis.  Recently they started to be used in drug storage and delivery as well as in medical imaging and sensing. One of the most important challenges in drug delivery research is the efficient transport and release of drugs in the body using nontoxic nanocarriers to improve their activity and MOFs present the potential characteristics to solve this problem since they combine a high pore volume, a regular porosity and the presence of tunable organic groups within the framework, which allow the modulation of the structure of the framework as well as of the pore size. From a series of different active pharmaceutical ingredients (API) tested, results with nalidixic acid have shown to be promising. Nalidixic acid is a quinolone antibiotic used for the treatment of urinary tract infections, which can also act as bacteriostatic and as bactericidal. Bio-inspired networks of this API with safe metals are being successfully explored. Coordination with different metals, including Zn, Mn and Mg, yielded novel coordination networks. The use  of second ligands, such as oxalic and citric acids, has shown to be successful and it represents a pathway to obtain stuctures with higher porosity. Most of these new forms can be obtained by mechanochemistry, an efficient and environment-friendly synthetic technique.  The solubility and stability of these compounds sustents their viability for pharmaceutical applications.

Biography:

Dominic Ormerod is a Senior Researcher in the Green Chemical Technology group at VITO, which he joined in February 2012. After obtaining a PhD in Organic Chemistry, (1998, Univesité Catholique de Louvain, Louvain-La-Neuve Belgium) in the group of Prof. I. E. Markó, he moved to Janssen Pharmaceutica, Beerse, Belgium in the Department of Chemical Process Development, where he worked from 1998 until January 2012. In his current role, he Leads research directed towards membrane assisted process intensification. He is the author of 14 publications and inventor on 9 patents.

Abstract:

Successful chemical production of molecules whilst simultaneously reducing the environmental impact of the process relies not only on more efficient reactions but also on developments in reactor and separation technology. Recent decades have also witnessed a significant growth in industrial interest in solvent based separations using membranes stable to organic solvents. Thanks to its non-thermal, hence mild and energy-efficient character, organic solvent nanofiltration (OSN) is capable of efficiently concentrating and purifying valuable target molecules, removing post-reaction residues and recovery of spent solvents or catalysts. Furthermore, process intensification can be achieved by the integration of OSN with chemical reactions, resulting in significant gains in purity and/or capacity, and concomitant decreases in energy demand, raw material usage and/or waste volumes. One particular development deals with reactions which require, for various reasons, a high substrate dilution in order to avoid the formation of unwanted secondary products. This results in large volumes of solvent being necessary to produce relatively small quantities of the desired molecule. A typical case where such diluted conditions are required is the synthesis of macrocyclic molecules. Despite this drawback, globally several macrocyclic compounds are being produced on an industrial scale, however in a very inefficient manner. In order to address the economic and environmental shortcomings of high dilution reactions, VITO has developed a processing method that incorporates in line solvent recycling via OSN. This membrane-assisted methodology allows for significant reductions in the solvent load without loss in product yield or analytical purity as compared to a batch process. In collaboration with industrial partners, the potential of this novel methodology has been demonstrated in the preparation of numerous macrocyclic molecules.