Asit Chakraborti - Academia.edu (original) (raw)

Papers by Asit Chakraborti

Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a ro... more Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a route to the discovery of new drugs. Understanding the macromolecule-ligand interactions and validation of method used for docking and virtual screening of chemical databases is crucial step in structure-based design. We carried out molecular docking for a set of eighty two structurally diverse COX-1/COX-2 inhibitors including traditional NSAIDs and the recently developed coxibs such as celecoxib, rofecoxib, valdecoxib and etoricoxib using FlexX method to find out how good this method differentiate between the active and inactive compounds. Method. FlexX is one of the fast flexible docking method that uses an incremental construction algorithm to place ligands into an active site. The scoring function (empirical binding free energy) of the FlexX used to estimate the free binding energy of the protein-ligand complex is called F_score. Results. Reproducibility of the experimental conformatio...

New Journal of Chemistry

Visible light promoted tandem dehydrogenation-deaminative cyclocondensation of arylmethyl/ethyl a... more Visible light promoted tandem dehydrogenation-deaminative cyclocondensation of arylmethyl/ethyl amines with ortho-phenylenediamines under aerobic conditions is reported for the synthesis of 2-aryl benzimidazoles/quinoxalines.

Organic & Biomolecular Chemistry

X-ray crystallography data S153-S156 10 Computational Methods S157 11 Cartesian Coordinates of 1w... more X-ray crystallography data S153-S156 10 Computational Methods S157 11 Cartesian Coordinates of 1w, 1w' and 1w-I 2 S158-S160 12 NBO Charges on 1w, 1w-HY and 1w-I 2 S160

Chemistry (Weinheim an der Bergstrasse, Germany), Jan 25, 2018

Remote N-heterocyclic carbenes (rNHCs), such as N-methyl-4-pyridylidene, are known to form coordi... more Remote N-heterocyclic carbenes (rNHCs), such as N-methyl-4-pyridylidene, are known to form coordination complexes with TMs. Herein, it is established that rNHCs can also coordinate to the N centre. Synthesis of some novel divalent N complexes with the general formula (rNHC)→N ←(NHC) and (rNHC)→N ←(rNHC) was achieved, and X-ray diffraction studies supported the coordination bond character between the rNHCs and the N centre. Quantum chemical analysis established the presence of divalent N character at the central nitrogen in these systems.

The Journal of Organic Chemistry

The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyo... more The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via the 5-endo-trig process contrary to Baldwin's rule. On the other hand, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via the 6-exo-trig process in compliance with Baldwin's rule. The mechanistic insights of these cyclocondensation reactions using the hard-soft acid-base principle, quantum chemical calculations (density functional theory), and orbital interaction studies rationalize the selectivity switch of benzothiazole-2-carboxylates versus benzazine-3-ones/benzazine-2,3-diones. The presence of water facilitates these cyclocondensation reactions by lowering of the energy barrier.

European Journal of Medicinal Chemistry, 2017

Guanylthiourea (GTU) derivatives were identified as possible anti-malarial agents, recently, usin... more Guanylthiourea (GTU) derivatives were identified as possible anti-malarial agents, recently, using in vitro studies on Plasmodium falciparum. This article gives an account of the in vivo anti-malarial activity of GTU derivatives against experimental rodent malaria. A total of 20 synthesized GTU derivatives were evaluated for in vivo antimalarial activity, out of which six showed encouraging results; one compound appeared to have curative potential. Molecular docking and molecular dynamics analysis were carried out to understand the molecular level interactions.

The Journal of Organic Chemistry, 2017

Cross-dehydrogenative coupling of biorelevant heterocyclic scaffolds with arylmethanes for aroyla... more Cross-dehydrogenative coupling of biorelevant heterocyclic scaffolds with arylmethanes for aroylation during Pd(II)-catalyzed C(sp(2))-H activation has been achieved through dioxygen activation by NHPI. Mass spectrometry and (1)H NMR based kinetic isotope effect studies revealed C-H bond activation as the rate-determining step. Radical scavenging experiments indicated a radical pathway. The (1)H NMR of an aliquot of reaction mixture and in situ trapping with 2-aminothiophenol revealed the formation of aldehyde during aerobic oxidation of the arylmethanes. The reaction has broad scope for different variations of the aroyl source and the directing group that includes benzothiazole, benzooxazole, pyridine, quinoxaline, pyrimidine, and azoarene. The benzylic methylene moiety was found to be the source of the aroyl carbon with the benzyl ether moiety being the most preferred followed by the carbonyl group of aryl aldehyde and the aryl methane. However, the ease of availability of aryl methanes makes them the most attractive as an aroyl source. A time dependent selective mono- and bis-aroylation can be achieved. The 1,3-diarylpyrimidines exhibited regioselective aroylation of the 2-phenyl moiety irrespective of the absence or presence of any substitutent (electron withdrawing or electron donating) in the 3-phenyl moiety. For unsymmetrical azoarenes, selective aroylation took place in the phenyl moiety bearing the substituent.

Journal of pharmaceutical and biomedical analysis, Jan 20, 2017

Combination therapy with the use of fixed-dose combinations (FDCs) is evincing increasing interes... more Combination therapy with the use of fixed-dose combinations (FDCs) is evincing increasing interest of prescribers, manufacturers and even regulators, evidently due to the primary benefit of improved patient compliance. However, owing to potential of drug-drug interaction, FDCs require closer scrutiny with respect to their physical and chemical stability. Accordingly, the purpose of the present study was to explore stability behavior of a popular antihypertensive combination of amlodipine besylate (AML) and losartan potassium (LST). Physical mixtures of the two drugs and multiple marketed formulations were stored under accelerated conditions of temperature and humidity (40°C/75% RH) in a stability chamber and samples were withdrawn after 1 and 3 months. The physical changes were observed visibly, while chemical changes were monitored by HPLC employing a method that could separate the two drugs and all other components present. The combination revealed strong physical instability and ...

The Journal of Organic Chemistry, 2016

Guanylhydrazones have been known for a long time and have wide applications in organic synthesis,... more Guanylhydrazones have been known for a long time and have wide applications in organic synthesis, medicinal chemistry and material science; however, little attention has been paid towards their electronic and structural properties. Quantum chemical analysis on several therapeutically important guanylhydrazones indicated that all of them prefer the azine tautomeric state (by about 3-12 kcal/mol). A set of simple and conjugated azines were designed using quantum chemical methods, whose tautomeric preference towards the azine tautomer is in the range of 3-8 kcal/mol. Twenty new azines were synthesized and isolated in their neutral state. Variable temperature NMR study suggests existence of the azine tautomer even at higher temperatures with no traces of the hydrazone tautomer. The crystal structures of two representative compounds confirmed that the title compounds prefer to exist in their azine tautomeric form.

Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a ro... more Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a route to the discovery of new drugs. Understanding the macromolecule-ligand interactions and validation of method used for docking and virtual screening of chemical databases is crucial step in structure-based design. We therefore carried out molecular docking for a set of eighty two structurally diverse COX-1/COX-2 inhibitors including traditional NSAIDs and the recent developed coxibs using FlexX method to find out how good this method differentiate between the active and inactive compounds. Method. FlexX is one of the fast flexible docking method that uses an incremental construction algorithm to place ligands into an active site. The scoring function (empirical binding free energy) of the flexX used to estimate the free binding energy of the protein-ligand complex is called F_score. Results. Reproducibility of the experimental conformations of the bound ligands such as SC-558, indomethacin, flurbiprofen indicates the better performance of FlexX method. Good correlation between the standard FlexX score (F_score) and the COX-2 inhibitory activity (pIC 50) was observed. Simple linear regression analysis provided the correlation coefficient values of 0.731 and 0.670 for two classes of COX-2 inhibitors. Conclusions. Flexible docking of eighty two structurally diverse COX-2 inhibitors have been successfully carried out. Some false positives and false negatives were observed but considering the limitations of the available docking programs, the results are encouraging. The detailed analysis of the resulted COX-2-ligand complexes may improve our knowledge in understanding the binding interactions in detail. Thus, this study will be useful for the design of novel COX-2 inhibitors based on docking and the resulted bioactive conformations of the ligands will be useful in building structure-based 3-D QSAR model.

European Journal of Medicinal Chemistry, 2016

In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3β inhibitors. Mo... more In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3β inhibitors. Molecular docking analysis was carried to design a series of compounds, which were synthesized using substituted thiourea, 2-bromoacetophenones and benzaldehydes. Out of the twenty five compounds synthesized during this work, the in vitro evaluation against GSK-3 led to the identification of nine compounds with activity in lower nano-molar range (2-85 nM). Further, in vitro evaluation against CDK-2 showed five compounds to be selective towards GSK-3.

Catal. Sci. Technol., 2016

Unprecedented Pd–Ag/Cu–Ag nanocluster-catalyst switch leads to a phenazine/azoarene twist for non... more Unprecedented Pd–Ag/Cu–Ag nanocluster-catalyst switch leads to a phenazine/azoarene twist for non-radical mode C–H activation vs. radical mode N–N self-coupling of anilines.

European Journal of Medicinal Chemistry, 2016

Novel Y-shaped barbituric acid (BA) derivatives have been designed using rational methods includi... more Novel Y-shaped barbituric acid (BA) derivatives have been designed using rational methods including molecular docking. Fourteen novel compounds were synthesized using hydroxyl group protection-deprotection strategies for PPARγ activation. Competitive binding analysis of the synthesized molecules using time-resolved fluorescence resonance energy transfer (FRET) method was carried out, and the IC50 values were determined. The symmetrically substituted derivatives have shown greater binding affinity than unsymmetrically substituted derivatives. Nitrobenzyl and cyanophenyl substituted derivatives have shown reasonable binding affinities (10.1 and 6.5 μM, respectively), while mono and diacetate derivatives were found inactive. Molecular dynamics simulations show that the designed compounds have interaction profiles similar to partial agonists. The most significant finding of our study is that BA derivatives with symmetrically substituted weakly polar side chains result in the desired moderate level of PPARγ binding affinities.

Chem. Commun., 2016

Pd–Ag binary nanocluster-catalysed synchronous double C–N bond formation via C–H activation durin... more Pd–Ag binary nanocluster-catalysed synchronous double C–N bond formation via C–H activation during self-coupling of anilines to form phenazines.

Current medicinal chemistry, 2016

The PDE4 enzyme has been proven to be a versatile drug target for therapeutics to treat diverse d... more The PDE4 enzyme has been proven to be a versatile drug target for therapeutics to treat diverse disease conditions such as asthma, COPD, diabetes, Huntington's disease, and various other inflammatory disorders. The treatment of COPD is the most studied utility for PDE4 inhibitors due to their ability to inhibit inflammatory cell responses. Roflumilast is the only approved drug belonging to this class to treat COPD and has shown significant results in the treatment of asthmatic patients. This perspective highlights the pharmacological details of roflumilast and cilomilast. Moreover, efforts have been made to justify the superiority of roflumilast over cilomilast by detailed comparison of their pharmacological, pharmacokinetic, pharmacodynamic properties and structural features. Several other molecules, with promising PDE4 inhibitory activity have also been highlighted. Commonly associated side effects with this class of compounds, their management, and future direction towards th...

Synthesis, 2015

An ecofriendly approach for the synthesis of highly substituted tetrahydropyridines by an ‘on-wat... more An ecofriendly approach for the synthesis of highly substituted tetrahydropyridines by an ‘on-water’ multicomponent reaction has been demonstrated. The use of water as the reaction medium is essential under the catalytic influence of a surfactant. The use of a variety of anionic, cationic, and non-ionic surfactants in water was examined and the reaction was successfully catalyzed by anionic surfactants sodium dioctyl sulfosuccinate (SDOSS) and sodium dodecyl sulfate (SDS), with the former being superior. The use of an organic solvent together with a catalytic amount of sodium dioctyl sulfosuccinate to form homogeneous conditions afforded inferior yields and highlighted the specific role of water through the creation of microreactors at the water surfactant interface. A mechanistic insight for the five-component reaction leading to the formation of tetrahydropyridines is provided invoking a tandem inter- and intramolecular Mannich reaction pathway.

Chemistry (Weinheim an der Bergstrasse, Germany), Jan 30, 2015

The dative-bond representation (L→E) in compounds with main group elements (E) has triggered exte... more The dative-bond representation (L→E) in compounds with main group elements (E) has triggered extensive debate in the recent past. The scope and limits of this nonclassical coordination bond warrant comprehensive exploration. Particularly compounds with (L→N←L')(+) arrangement are of special interest because of their therapeutic importance. This work reports the design and synthesis of novel chemical species with the general structural formula (L→N←L')(+) carrying the unusual ligand cyclohexa-2,5-diene-4-(diaminomethynyl)-1-ylidene. Four species belonging to the (L→N←L')(+) class carrying this unconventional ligand were synthesized. Quantum chemical and X-ray diffraction analyses showed that the electronic and geometric parameters are consistent with those of already reported divalent N(I) compounds. The molecular orbital analysis, geometric parameters, and spectral data clearly support the L→N and N←L' interactions in these species. The newly identified ligand has th...

Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a ro... more Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a route to the discovery of new drugs. Understanding the macromolecule-ligand interactions and validation of method used for docking and virtual screening of chemical databases is crucial step in structure-based design. We carried out molecular docking for a set of eighty two structurally diverse COX-1/COX-2 inhibitors including traditional NSAIDs and the recently developed coxibs such as celecoxib, rofecoxib, valdecoxib and etoricoxib using FlexX method to find out how good this method differentiate between the active and inactive compounds. Method. FlexX is one of the fast flexible docking method that uses an incremental construction algorithm to place ligands into an active site. The scoring function (empirical binding free energy) of the FlexX used to estimate the free binding energy of the protein-ligand complex is called F_score. Results. Reproducibility of the experimental conformatio...

New Journal of Chemistry

Visible light promoted tandem dehydrogenation-deaminative cyclocondensation of arylmethyl/ethyl a... more Visible light promoted tandem dehydrogenation-deaminative cyclocondensation of arylmethyl/ethyl amines with ortho-phenylenediamines under aerobic conditions is reported for the synthesis of 2-aryl benzimidazoles/quinoxalines.

Organic & Biomolecular Chemistry

X-ray crystallography data S153-S156 10 Computational Methods S157 11 Cartesian Coordinates of 1w... more X-ray crystallography data S153-S156 10 Computational Methods S157 11 Cartesian Coordinates of 1w, 1w' and 1w-I 2 S158-S160 12 NBO Charges on 1w, 1w-HY and 1w-I 2 S160

Chemistry (Weinheim an der Bergstrasse, Germany), Jan 25, 2018

Remote N-heterocyclic carbenes (rNHCs), such as N-methyl-4-pyridylidene, are known to form coordi... more Remote N-heterocyclic carbenes (rNHCs), such as N-methyl-4-pyridylidene, are known to form coordination complexes with TMs. Herein, it is established that rNHCs can also coordinate to the N centre. Synthesis of some novel divalent N complexes with the general formula (rNHC)→N ←(NHC) and (rNHC)→N ←(rNHC) was achieved, and X-ray diffraction studies supported the coordination bond character between the rNHCs and the N centre. Quantum chemical analysis established the presence of divalent N character at the central nitrogen in these systems.

The Journal of Organic Chemistry

The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyo... more The cyclocondensation reaction of 2-aminothiophenols with 1,2-biselectrophiles such as ethyl glyoxalate and diethyl oxalate in aqueous medium leads to the formation of benzothiazole-2-carboxylates via the 5-endo-trig process contrary to Baldwin's rule. On the other hand, the reaction of 2-aminophenols/anilines produced the corresponding benzazine-3-ones or benzazine-2,3-diones via the 6-exo-trig process in compliance with Baldwin's rule. The mechanistic insights of these cyclocondensation reactions using the hard-soft acid-base principle, quantum chemical calculations (density functional theory), and orbital interaction studies rationalize the selectivity switch of benzothiazole-2-carboxylates versus benzazine-3-ones/benzazine-2,3-diones. The presence of water facilitates these cyclocondensation reactions by lowering of the energy barrier.

European Journal of Medicinal Chemistry, 2017

Guanylthiourea (GTU) derivatives were identified as possible anti-malarial agents, recently, usin... more Guanylthiourea (GTU) derivatives were identified as possible anti-malarial agents, recently, using in vitro studies on Plasmodium falciparum. This article gives an account of the in vivo anti-malarial activity of GTU derivatives against experimental rodent malaria. A total of 20 synthesized GTU derivatives were evaluated for in vivo antimalarial activity, out of which six showed encouraging results; one compound appeared to have curative potential. Molecular docking and molecular dynamics analysis were carried out to understand the molecular level interactions.

The Journal of Organic Chemistry, 2017

Cross-dehydrogenative coupling of biorelevant heterocyclic scaffolds with arylmethanes for aroyla... more Cross-dehydrogenative coupling of biorelevant heterocyclic scaffolds with arylmethanes for aroylation during Pd(II)-catalyzed C(sp(2))-H activation has been achieved through dioxygen activation by NHPI. Mass spectrometry and (1)H NMR based kinetic isotope effect studies revealed C-H bond activation as the rate-determining step. Radical scavenging experiments indicated a radical pathway. The (1)H NMR of an aliquot of reaction mixture and in situ trapping with 2-aminothiophenol revealed the formation of aldehyde during aerobic oxidation of the arylmethanes. The reaction has broad scope for different variations of the aroyl source and the directing group that includes benzothiazole, benzooxazole, pyridine, quinoxaline, pyrimidine, and azoarene. The benzylic methylene moiety was found to be the source of the aroyl carbon with the benzyl ether moiety being the most preferred followed by the carbonyl group of aryl aldehyde and the aryl methane. However, the ease of availability of aryl methanes makes them the most attractive as an aroyl source. A time dependent selective mono- and bis-aroylation can be achieved. The 1,3-diarylpyrimidines exhibited regioselective aroylation of the 2-phenyl moiety irrespective of the absence or presence of any substitutent (electron withdrawing or electron donating) in the 3-phenyl moiety. For unsymmetrical azoarenes, selective aroylation took place in the phenyl moiety bearing the substituent.

Journal of pharmaceutical and biomedical analysis, Jan 20, 2017

Combination therapy with the use of fixed-dose combinations (FDCs) is evincing increasing interes... more Combination therapy with the use of fixed-dose combinations (FDCs) is evincing increasing interest of prescribers, manufacturers and even regulators, evidently due to the primary benefit of improved patient compliance. However, owing to potential of drug-drug interaction, FDCs require closer scrutiny with respect to their physical and chemical stability. Accordingly, the purpose of the present study was to explore stability behavior of a popular antihypertensive combination of amlodipine besylate (AML) and losartan potassium (LST). Physical mixtures of the two drugs and multiple marketed formulations were stored under accelerated conditions of temperature and humidity (40°C/75% RH) in a stability chamber and samples were withdrawn after 1 and 3 months. The physical changes were observed visibly, while chemical changes were monitored by HPLC employing a method that could separate the two drugs and all other components present. The combination revealed strong physical instability and ...

The Journal of Organic Chemistry, 2016

Guanylhydrazones have been known for a long time and have wide applications in organic synthesis,... more Guanylhydrazones have been known for a long time and have wide applications in organic synthesis, medicinal chemistry and material science; however, little attention has been paid towards their electronic and structural properties. Quantum chemical analysis on several therapeutically important guanylhydrazones indicated that all of them prefer the azine tautomeric state (by about 3-12 kcal/mol). A set of simple and conjugated azines were designed using quantum chemical methods, whose tautomeric preference towards the azine tautomer is in the range of 3-8 kcal/mol. Twenty new azines were synthesized and isolated in their neutral state. Variable temperature NMR study suggests existence of the azine tautomer even at higher temperatures with no traces of the hydrazone tautomer. The crystal structures of two representative compounds confirmed that the title compounds prefer to exist in their azine tautomeric form.

Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a ro... more Motivation. Three-dimensional structures of pharmacologically important macromolecules offer a route to the discovery of new drugs. Understanding the macromolecule-ligand interactions and validation of method used for docking and virtual screening of chemical databases is crucial step in structure-based design. We therefore carried out molecular docking for a set of eighty two structurally diverse COX-1/COX-2 inhibitors including traditional NSAIDs and the recent developed coxibs using FlexX method to find out how good this method differentiate between the active and inactive compounds. Method. FlexX is one of the fast flexible docking method that uses an incremental construction algorithm to place ligands into an active site. The scoring function (empirical binding free energy) of the flexX used to estimate the free binding energy of the protein-ligand complex is called F_score. Results. Reproducibility of the experimental conformations of the bound ligands such as SC-558, indomethacin, flurbiprofen indicates the better performance of FlexX method. Good correlation between the standard FlexX score (F_score) and the COX-2 inhibitory activity (pIC 50) was observed. Simple linear regression analysis provided the correlation coefficient values of 0.731 and 0.670 for two classes of COX-2 inhibitors. Conclusions. Flexible docking of eighty two structurally diverse COX-2 inhibitors have been successfully carried out. Some false positives and false negatives were observed but considering the limitations of the available docking programs, the results are encouraging. The detailed analysis of the resulted COX-2-ligand complexes may improve our knowledge in understanding the binding interactions in detail. Thus, this study will be useful for the design of novel COX-2 inhibitors based on docking and the resulted bioactive conformations of the ligands will be useful in building structure-based 3-D QSAR model.

European Journal of Medicinal Chemistry, 2016

In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3β inhibitors. Mo... more In this work, iminothiazolidin-4-one derivatives were explored as selective GSK-3β inhibitors. Molecular docking analysis was carried to design a series of compounds, which were synthesized using substituted thiourea, 2-bromoacetophenones and benzaldehydes. Out of the twenty five compounds synthesized during this work, the in vitro evaluation against GSK-3 led to the identification of nine compounds with activity in lower nano-molar range (2-85 nM). Further, in vitro evaluation against CDK-2 showed five compounds to be selective towards GSK-3.

Catal. Sci. Technol., 2016

Unprecedented Pd–Ag/Cu–Ag nanocluster-catalyst switch leads to a phenazine/azoarene twist for non... more Unprecedented Pd–Ag/Cu–Ag nanocluster-catalyst switch leads to a phenazine/azoarene twist for non-radical mode C–H activation vs. radical mode N–N self-coupling of anilines.

European Journal of Medicinal Chemistry, 2016

Novel Y-shaped barbituric acid (BA) derivatives have been designed using rational methods includi... more Novel Y-shaped barbituric acid (BA) derivatives have been designed using rational methods including molecular docking. Fourteen novel compounds were synthesized using hydroxyl group protection-deprotection strategies for PPARγ activation. Competitive binding analysis of the synthesized molecules using time-resolved fluorescence resonance energy transfer (FRET) method was carried out, and the IC50 values were determined. The symmetrically substituted derivatives have shown greater binding affinity than unsymmetrically substituted derivatives. Nitrobenzyl and cyanophenyl substituted derivatives have shown reasonable binding affinities (10.1 and 6.5 μM, respectively), while mono and diacetate derivatives were found inactive. Molecular dynamics simulations show that the designed compounds have interaction profiles similar to partial agonists. The most significant finding of our study is that BA derivatives with symmetrically substituted weakly polar side chains result in the desired moderate level of PPARγ binding affinities.

Chem. Commun., 2016

Pd–Ag binary nanocluster-catalysed synchronous double C–N bond formation via C–H activation durin... more Pd–Ag binary nanocluster-catalysed synchronous double C–N bond formation via C–H activation during self-coupling of anilines to form phenazines.

Current medicinal chemistry, 2016

The PDE4 enzyme has been proven to be a versatile drug target for therapeutics to treat diverse d... more The PDE4 enzyme has been proven to be a versatile drug target for therapeutics to treat diverse disease conditions such as asthma, COPD, diabetes, Huntington's disease, and various other inflammatory disorders. The treatment of COPD is the most studied utility for PDE4 inhibitors due to their ability to inhibit inflammatory cell responses. Roflumilast is the only approved drug belonging to this class to treat COPD and has shown significant results in the treatment of asthmatic patients. This perspective highlights the pharmacological details of roflumilast and cilomilast. Moreover, efforts have been made to justify the superiority of roflumilast over cilomilast by detailed comparison of their pharmacological, pharmacokinetic, pharmacodynamic properties and structural features. Several other molecules, with promising PDE4 inhibitory activity have also been highlighted. Commonly associated side effects with this class of compounds, their management, and future direction towards th...

Synthesis, 2015

An ecofriendly approach for the synthesis of highly substituted tetrahydropyridines by an ‘on-wat... more An ecofriendly approach for the synthesis of highly substituted tetrahydropyridines by an ‘on-water’ multicomponent reaction has been demonstrated. The use of water as the reaction medium is essential under the catalytic influence of a surfactant. The use of a variety of anionic, cationic, and non-ionic surfactants in water was examined and the reaction was successfully catalyzed by anionic surfactants sodium dioctyl sulfosuccinate (SDOSS) and sodium dodecyl sulfate (SDS), with the former being superior. The use of an organic solvent together with a catalytic amount of sodium dioctyl sulfosuccinate to form homogeneous conditions afforded inferior yields and highlighted the specific role of water through the creation of microreactors at the water surfactant interface. A mechanistic insight for the five-component reaction leading to the formation of tetrahydropyridines is provided invoking a tandem inter- and intramolecular Mannich reaction pathway.

Chemistry (Weinheim an der Bergstrasse, Germany), Jan 30, 2015

The dative-bond representation (L→E) in compounds with main group elements (E) has triggered exte... more The dative-bond representation (L→E) in compounds with main group elements (E) has triggered extensive debate in the recent past. The scope and limits of this nonclassical coordination bond warrant comprehensive exploration. Particularly compounds with (L→N←L')(+) arrangement are of special interest because of their therapeutic importance. This work reports the design and synthesis of novel chemical species with the general structural formula (L→N←L')(+) carrying the unusual ligand cyclohexa-2,5-diene-4-(diaminomethynyl)-1-ylidene. Four species belonging to the (L→N←L')(+) class carrying this unconventional ligand were synthesized. Quantum chemical and X-ray diffraction analyses showed that the electronic and geometric parameters are consistent with those of already reported divalent N(I) compounds. The molecular orbital analysis, geometric parameters, and spectral data clearly support the L→N and N←L' interactions in these species. The newly identified ligand has th...