Frequency and Importance of Six Functional Groups that Play a Role in Drug Discovery

Small molecules are composed of chemical functional groups; they are sets of connected atoms or atom groups that determine properties and reactivity of the parent molecule. DrugBank is a rich source of information that containing molecular data about small molecules, their mechanisms, pharmaceutical interaction and targets. In this study, After collecting data of small drug molecules from DrugBank database and classifying them in different categories based on their mechanism of action, the therapeutic properties of the molecules were recorded. Finally, the functional group from the pharmaceutical structures were elucidated and registered for each group. The functional groups were divided into five distinct groups in drug design, and a correlation between identified functional group to pharmaceutical structure were indicated according to the classified functional groups of small molecule and drug categories; then defined their frequency in categories, at high abundant functional group present in categories reported. The most frequent rings were benzene and cyclohexane; the common acid functionality had been acetate (carboxy-); three most repeated saturated heterocyles are piperidine, piperazine and azetidine; among the unsaturated heterocyles, pyridine, imidazole and indole are noticed; This database, that may be guidance for researchers with the aim at designing new drugs.

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Methods of Synthesis of Remdesivir, Favipiravir, Hydroxychloroquine, and Chloroquine: Four Small Molecules Repurposed for Clinical Trials during the Covid-19 Pandemic

Synthesis ◽

10.1055/s-0040-1707386 ◽

2020 ◽

Vol 52 (24) ◽

pp. 3735-3750 ◽

Cited By ~ 1

Author(s):

Nader Al Bujuq

Keyword(s):

Small Molecules ◽

New Drugs ◽

Reference Source ◽

The Novel ◽

Efficacy And Safety ◽

Health Measures ◽

Drug Molecules ◽

Agency Support ◽

Methods Of Synthesis ◽

Novel Coronavirus

AbstractThe novel coronavirus (COVID-19) disease has rapidly evolved into a sweeping pandemic despite public health measures. Screening and development of new vaccines and antivirals are expensive and time consuming. However, the repositioning of available drugs is an essential and universal strategy in the development of new drugs and therefore should receive priority attention as well as international government and agency support. Significant drugs such as chloroquine, hydroxychloroquine, favipiravir and remdesivir, are currently undergoing clinical studies to test their efficacy and safety. Some promising results have been achieved thus far in the treatment of COVID-19. In this article we summarize and discuss the most common synthetic strategies to apply in the preparation of these drug molecules. It is hoped that this compendium will provide an accessible useful guide and reference source for scientists, researchers and academia in their battle against COVD-19.1 Introduction2 Synthesis of Chloroquine (CQ) and Hydroxychloroquine (HCQ)2.1 Synthesis of 4,7-Dichloroquinoline 1 2.2 Synthesis of 2-Amino-5-(diethylamino)pentane (Novoldiamine) 2 2.3 Synthesis of 5-(N-Ethyl-N-2-hydroxyethylamino)-2-pentylamine 4 2.4 Developed Methods for Synthesis of Chloroquine and Hydroxychloroquine2.5 Synthesis of (R)-Chloroquine, (S)-Chloroquine, (R)-Hydroxychloroquine and (S)-Hydroxychloroquine3 Synthesis of Favipiravir (Avigan)4 Synthesis of Remdesivir5 Conclusion

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Spatial Representation of Hydrocarbon Odorants in the Ventrolateral Zones of the Rat Olfactory Bulb

Journal of Neurophysiology ◽

10.1152/jn.00873.2004 ◽

2005 ◽

Vol 93 (2) ◽

pp. 1007-1019 ◽

Cited By ~ 37

Author(s):

Kei M. Igarashi ◽

Kensaku Mori

Keyword(s):

Olfactory Bulb ◽

Functional Groups ◽

Spatial Representation ◽

Functional Group ◽

Odorant Receptor ◽

Systematic Difference ◽

Intrinsic Signal ◽

Molecular Features ◽

The Common ◽

Polar Functional Groups

The glomerular sheet of the olfactory bulb (OB) forms odorant receptor maps that are parceled into zones. We previously reported the molecular receptive range (MRR) property of individual glomeruli in the dorsal zone (zone 1) of the OB and showed that polar functional groups play a major role in activating glomeruli in this zone. However, the MRR property of glomeruli in zones 2–4 is not well understood yet. Using the method of intrinsic signal imaging, we recorded odorant-induced glomerular activity from the ventrolateral surface (zones 2–4) of rat OB. While hydrocarbon odorants that lack polar functional groups activate only a few glomeruli in zone 1, we found that a series of hydrocarbon odorants consistently activated many glomeruli in the ventrolateral surface. The hydrocarbon-responsive glomeruli were grouped into two clusters; glomeruli in one cluster (cluster H) responded to benzene-family hydrocarbons but not to cyclic terpene hydrocarbons. Glomeruli in the other cluster (cluster I) responded to both classes of hydrocarbons. Detailed analyses of MRR properties of individual glomeruli using hydrocarbon odorants and polar-functional-group-containing odorants showed that the common and characteristic molecular features effective in activating glomeruli in the clusters H and I are the hydrocarbon skeleton. These results suggest that ORs represented by glomeruli in these clusters recognize primarily the hydrocarbon skeleton of odorants, and thus imply a systematic difference in the manner of recognizing odorant molecular features between ORs in zone 1 and ORs in zones 2–4.

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HobPre: accurate prediction of human oral bioavailability for small molecules

Journal of Cheminformatics ◽

10.1186/s13321-021-00580-6 ◽

2022 ◽

Vol 14 (1) ◽

Author(s):

Min Wei ◽

Xudong Zhang ◽

Xiaolin Pan ◽

Bo Wang ◽

Changge Ji ◽

...

Keyword(s):

Drug Development ◽

Small Molecules ◽

Oral Bioavailability ◽

Computational Models ◽

Experimental Tests ◽

New Drugs ◽

Drug Candidates ◽

Drug Molecules ◽

Key Factor ◽

Input Variables

AbstractHuman oral bioavailability (HOB) is a key factor in determining the fate of new drugs in clinical trials. HOB is conventionally measured using expensive and time-consuming experimental tests. The use of computational models to evaluate HOB before the synthesis of new drugs will be beneficial to the drug development process. In this study, a total of 1588 drug molecules with HOB data were collected from the literature for the development of a classifying model that uses the consensus predictions of five random forest models. The consensus model shows excellent prediction accuracies on two independent test sets with two cutoffs of 20% and 50% for classification of molecules. The analysis of the importance of the input variables allowed the identification of the main molecular descriptors that affect the HOB class value. The model is available as a web server at www.icdrug.com/ICDrug/ADMET for quick assessment of oral bioavailability for small molecules. The results from this study provide an accurate and easy-to-use tool for screening of drug candidates based on HOB, which may be used to reduce the risk of failure in late stage of drug development. Graphical Abstract

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Broad Assessment of Bioactivity of a Collection of Spiroindane Pyrrolidines Through “Cell Painting”

10.26434/chemrxiv.11977707 ◽

2020 ◽

Author(s):

Zarko Boskovic ◽

Manvendra Singh ◽

Zachary Pearson ◽

Nathan Garza

Keyword(s):

Biological Activity ◽

Small Molecules ◽

Functional Groups ◽

Organelle Morphology

A collection of small molecules has been synthesized by composing photo-cycloaddition, C-H functionalization, and N-capping strategies. Multidimensional biological fingerprints of molecules comprising this collection have been recorded as changes in cell and organelle morphology. This untargeted, phenotypic approach allowed for a broad assessment of biological activity to be determined. Reproducibility and the magnitude of measured fingerprints revealed activity of several treatments. Reactive functional groups, such as imines, dominated the observed activity. Two non-reactive candidate compounds with distinct bioactivity fingerprints were identified, as well.

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Catalytic Synthesis of Cyclic Guanidines via Hydrogen Atom Transfer and Radical-Polar Crossover

10.26434/chemrxiv.13318421.v1 ◽

2020 ◽

Author(s):

Shunya Ohuchi ◽

Hiroki Koyama ◽

Hiroki Shigehisa

Keyword(s):

Hydrogen Atom ◽

Functional Group ◽

Hydrogen Atom Transfer ◽

Catalytic Synthesis ◽

Membered Ring ◽

Biologically Active ◽

Atom Transfer ◽

Powerful Method ◽

Protective Groups ◽

The Common

A catalytic synthesis of cyclic guanidines, which are found in many biologically active compounds and natu-ral products, was developed, wherein transition-metal hydrogen atom transfer and radical-polar crossover were employed. This mild and functional-group tolerant process enabled the cyclization of alkenyl guanidines bearing common protective groups, such as Cbz and Boc. This powerful method not only provided the common 5- and 6-membered rings but also an unusual 7-membered ring. The derivatization of the products afforded various heterocycles. We also investigated the se-lective cyclization of mono-protected or hetero-protected (TFA and Boc) alkenyl guanidines and their further derivatiza-tions.

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Computational and Experimental Binding Mechanism of DNA-drug Interactions

Current Pharmaceutical Design ◽

10.2174/1381612824666181106101448 ◽

2019 ◽

Vol 24 (32) ◽

pp. 3739-3757 ◽

Cited By ~ 2

Author(s):

Chandrabose Selvaraj ◽

Sanjeev K. Singh

Keyword(s):

Small Molecules ◽

Self Assembly ◽

Genetic Material ◽

Dna Interaction ◽

Significant Feature ◽

Drug Molecules ◽

Potential Applications ◽

Novel Drug ◽

Groove Binders ◽

Molecular Docking And Dynamics

Nucleic acid is the key unit and a predominant genetic material for interpreting the fundamental basis of genetic information in an organism and now it is used for the evolution of a novel group of therapeutics. To identify the potential impact on the biological science, it receives high recognition in therapeutic applications. Due to its selective recognition of molecular targets and pathways, DNA significantly imparts tremendous specificity of action. Examining the properties of DNA holds numerous advantages in assembly, interconnects, computational elements, along with potential applications of DNA self-assembly and scaffolding include nanoelectronics, biosensors, and programmable/autonomous molecular machines. The interaction of low molecular weight, small molecules with DNA is a significant feature in pharmacology. Based on the mode of binding mechanisms, small molecules are categorized as intercalators and groove binders having a significant role in target-based drug development. The understanding mechanism of drug-DNA interaction plays an important role in the development of novel drug molecules with more effective and lesser side effects. This article attempts to outline those interactions of drug-DNA with both experimental and computational advances, including ultraviolet (UV) -visible spectroscopy, fluorescent spectroscopy, circular dichroism, nuclear magnetic resonance (NMR), molecular docking and dynamics, and quantum mechanical applications.

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Resilience of Epiphytic Lichens to Combined Effects of Increasing Nitrogen and Solar Radiation

Journal of Fungi ◽

10.3390/jof7050333 ◽

2021 ◽

Vol 7 (5) ◽

pp. 333

Author(s):

Lourdes Morillas ◽

Javier Roales ◽

Cristina Cruz ◽

Silvana Munzi

Keyword(s):

Global Change ◽

Solar Radiation ◽

Functional Groups ◽

Physiological Response ◽

Functional Group ◽

Environmental Drivers ◽

Combined Effects ◽

Environmental Stressor ◽

Comprehensive Understanding ◽

Direct Sunlight

Lichens are classified into different functional groups depending on their ecological and physiological response to a given environmental stressor. However, knowledge on lichen response to the synergistic effect of multiple environmental factors is extremely scarce, although vital to get a comprehensive understanding of the effects of global change. We exposed six lichen species belonging to different functional groups to the combined effects of two nitrogen (N) doses and direct sunlight involving both high temperatures and ultraviolet (UV) radiation for 58 days. Irrespective of their functional group, all species showed a homogenous response to N with cumulative, detrimental effects and an inability to recover following sunlight, UV exposure. Moreover, solar radiation made a tolerant species more prone to N pollution’s effects. Our results draw attention to the combined effects of global change and other environmental drivers on canopy defoliation and tree death, with consequences for the protection of ecosystems.

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Fensomea setacea, gen. & sp. nov. (Cladopyxidaceae, Dinophyceae), is neither gonyaulacoid nor peridinioid as inferred from morphological and molecular data

Scientific Reports ◽

10.1038/s41598-021-92107-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Marc Gottschling ◽

Maria Consuelo Carbonell-Moore ◽

Kenneth Neil Mertens ◽

Monika Kirsch ◽

Malte Elbrächter ◽

...

Keyword(s):

Molecular Data ◽

Character Evolution ◽

Ancestral State ◽

Close Relationship ◽

Regular Configuration ◽

The Common ◽

Morphological And Molecular Data ◽

Rrna Sequences

AbstractDinophyte evolution is essentially inferred from the pattern of thecal plates, and two different labelling systems are used for the important subgroups Gonyaulacales and Peridiniales. The partiform hypotheca of cladopyxidoid dinophytes fits into the morphological concepts of neither group, although they are assigned to the Gonyaulacales. Here, we describe the thecate dinophyte Fensomea setacea, gen. & sp. nov., which has a cladopyxidoid tabulation. The cells displayed a Kofoidean plate formula APC, 3′, 4a, 7″, 7C, 6S, 6′′′, 2′′′′, and slender processes were randomly distributed over the echinate or baculate surface. In addition, we obtained rRNA sequences of F. setacea, gen. & sp. nov., but dinophytes that exhibit a partiform hypotheca did not show a close relationship to Gonyaulacales. Character evolution of thecate dinophytes may have progressed from the ancestral state of six postcingular plates, and two more or less symmetrically arranged antapical plates, towards patterns of only five postcingular plates (Peridiniales) or more asymmetrical configurations (Gonyaulacales). Based on our phylogenetic reconsiderations the contact between the posterior sulcal plate and the first postcingular plate, as well as the contact between an antapical plate and the distalmost postcingular plate, do not represent a rare, specialized gonyaulacoid plate configuration (i.e., the partiform hypotheca of cladopyxidoid dinophytes). Instead, these contacts correspond to the common and regular configuration of peridinioid (and other) dinophytes.

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Diversity-oriented synthesis derived indole based spiro and fused small molecules kills artemisinin-resistant Plasmodium falciparum

Malaria Journal ◽

10.1186/s12936-021-03632-2 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Akshaykumar Nayak ◽

Himani Saxena ◽

Chandramohan Bathula ◽

Tarkeshwar Kumar ◽

Souvik Bhattacharjee ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Small Molecules ◽

New Drugs ◽

Developmental Cycle ◽

Oxygen Species ◽

Compound Library ◽

Diversity Oriented Synthesis ◽

Resistant Strains ◽

Acid Catalyzed

Abstract Background Despite numerous efforts to eradicate the disease, malaria continues to remain one of the most dangerous infectious diseases plaguing the world. In the absence of any effective vaccines and with emerging drug resistance in the parasite against the majority of anti-malarial drugs, the search for new drugs is urgently needed for effective malaria treatment. Methods The goal of the present study was to examine the compound library, based on indoles generated through diversity-oriented synthesis belonging to four different architecture, i.e., 1-aryltetrahydro/dihydro-β-carbolines and piperidine/pyrrolidine-fused indole derivatives, for their in vitro anti-plasmodial activity. Trifluoroacetic acid catalyzed transformation involving tryptamine and various aldehydes/ketones provided the library. Results Among all the compounds screened, 1-aryltetrahydro-β-carbolines 2 and 3 displayed significant anti-plasmodial activity against both the artemisinin-sensitive and artemisinin-resistant strain of Plasmodium falciparum. It was observed that these compounds inhibited the overall parasite growth in intra-erythrocytic developmental cycle (IDC) via reactive oxygen species-mediated parasitic death and thus could be potential anti-malarial compounds. Conclusion Overall the compounds 2 and 3 identified in this study shows promising anti-plasmodial activity that can kill both artemisinin-sensitive and artemisinin-resistant strains of P. falciparum.

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Protecting group-free, selective cross-coupling of alkyltrifluoroborates with borylated aryl bromides via photoredox/nickel dual catalysis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1509715112 ◽

2015 ◽

Vol 112 (39) ◽

pp. 12026-12029 ◽

Cited By ~ 66

Author(s):

Yohei Yamashita ◽

John C. Tellis ◽

Gary A. Molander

Keyword(s):

Small Molecules ◽

Functional Group ◽

Cross Coupling ◽

Differential Protection ◽

Coupling Reactions ◽

Protecting Group ◽

Cross Coupling Reactions ◽

Aryl Bromides ◽

Rapid Construction ◽

Metal Catalyzed

Orthogonal reactivity modes offer substantial opportunities for rapid construction of complex small molecules. However, most strategies for imparting orthogonality to cross-coupling reactions rely on differential protection of reactive sites, greatly reducing both atom and step economies. Reported here is a strategy for orthogonal cross-coupling wherein a mechanistically distinct activation mode for transmetalation of sp3-hybridized organoboron reagents enables C-C bond formation in the presence of various protected and unprotected sp2-hybridized organoborons. This manifold has the potential for broad application, because orthogonality is inherent to the activation mode itself. The diversification potential of this platform is shown in the rapid elaboration of a trifunctional lynchpin through various transition metal-catalyzed processes without nonproductive deprotection or functional group manipulation steps.

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