This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has change... more This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has changed the habits of many young adults, but still the uses of (novel) illicit substances remain high. Drug addiction and tolerance seem to be a major worldwide burden. Multiple drug use is not infrequent and it was associated with a higher incidence of major adverse events than single drug use. The emerging illicit substances will be discussed including their pharmacological effects and their chemical synthesis/structure. The goal of this review is to shed more light on such important aspects of illegality, commonly occurring in urban life. Better drug education, increased law enforcement, and rehabilitation programs should be undertaken to tackle a foremost world burden.
Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide a... more Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide an innovative link between thermoplastics and thermosets. The breakthrough idea behind CANs is to at least partially replace irreversible crosslinks in classic thermoset polymers with dynamic covalent bonds that allow for reversible polymer character and recyclability. Besides, CANs also offer other popular features such as self-healing, weldability, configurability, and shape memory. Most CANs are still petroleum-based, yet shifting toward more sustainable approaches is of the utmost interest. Considering this and the high abundance of lignocellulosic biomass, this perspective focuses on all the research found on lignin-based CANs, including both those starting from fractionated lignin and from lignin-based monomers. This is clearly a new branch within bio-based CANs that holds great potential in various industries. Additionally, some examples of thermoset polymers derived from the same lignin building blocks are given to showcase important chemical transformations that can be used for CANs design in the future. Although CAN design has been extended to many different types of bonds, imines and disulfides largely prevail in the current literature. Lastly, a SWOT (strengths, weaknesses, opportunities, and threats) analysis is presented, considering the performance, competition, opportunities, and drawbacks of lignin-derived CANs.
Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide a... more Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide an innovative link between thermoplastics and thermosets. The breakthrough idea behind CANs is to at least partially replace irreversible crosslinks in classic thermoset polymers with dynamic covalent bonds that allow for reversible polymer character and recyclability. Besides, CANs also offer other popular features such as self-healing, weldability, configurability, and shape memory. Most CANs are still petroleum-based, yet shifting toward more sustainable approaches is of the utmost interest. Considering this and the high abundance of lignocellulosic biomass, this perspective focuses on all the research found on lignin-based CANs, including both those starting from fractionated lignin and from lignin-based monomers. This is clearly a new branch within bio-based CANs that holds great potential in various industries. Additionally, some examples of thermoset polymers derived from the same lignin building blocks are given to showcase important chemical transformations that can be used for CANs design in the future. Although CAN design has been extended to many different types of bonds, imines and disulfides largely prevail in the current literature. Lastly, a SWOT (strengths, weaknesses, opportunities, and threats) analysis is presented, considering the performance, competition, opportunities, and drawbacks of lignin-derived CANs.
This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has change... more This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has changed the habits of many young adults, but still the uses of (novel) illicit substances remain high. Drug addiction and tolerance seem to be a major worldwide burden. Multiple drug use is not infrequent and it was associated with a higher incidence of major adverse events than single drug use. The emerging illicit substances will be discussed including their pharmacological effects and their chemical synthesis/structure. The goal of this review is to shed more light on such important aspects of illegality, commonly occurring in urban life. Better drug education, increased law enforcement, and rehabilitation programs should be undertaken to tackle a foremost world burden.
This review describes, from a chemical point of view, the top “blockbuster” small molecule orphan... more This review describes, from a chemical point of view, the top “blockbuster” small molecule orphan drugs according to their forecasted sales in 2026. Orphan drugs are intended for the treatment, prevention, or diagnosis of a rare disease or condition. These molecules are mostly addressed to the treatment of rare forms of cancer. The respiratory and central nervous systems represent other common therapeutic subcategories. This work will show how the orphan drugs market has significantly grown and will account for a consistent part of prescriptions by 2026.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This review describes the recently FDA-approved drugs (in the year 2022). Many of these products ... more This review describes the recently FDA-approved drugs (in the year 2022). Many of these products contain active moieties that FDA had not previously approved, either as a single ingredient or as part of a combination. These products frequently provide important new therapies for patients with multiple unmet diseases. The diverse small molecules are described according to the date of approval and their syntheses is discussed. This review comprises classical chemical scaffolds together with innovative drugs such as a deuterium-containing drug.
This review describes the recent Food and Drug Administration (FDA)-approved drugs (in the year 2... more This review describes the recent Food and Drug Administration (FDA)-approved drugs (in the year 2021) containing at least one halogen atom (covalently bound). The structures proposed throughout this work are grouped according to their therapeutical use. Their synthesis is presented as well. The number of halogenated molecules that are reaching the market is regularly preserved, and 14 of the 50 molecules approved by the FDA in the last year contain halogens. This underlines the emergent role of halogens and, in particular, of fluorine and chlorine in the preparation of drugs for the treatment of several diseases such as viral infections, several types of cancer, cardiovascular disease, multiple sclerosis, migraine and inflammatory diseases such as vasculitis.
Protein kinase CK1δ expression and activity is involved in different pathological situations that... more Protein kinase CK1δ expression and activity is involved in different pathological situations that include neuroinflammatory and neurodegenerative diseases. For this reason, protein kinase CK1δ has become a possible therapeutic target for these conditions. 5,6-fused bicyclic heteroaromatic systems that resemble adenine of ATP represent optimal scaffolds for the development of a new class of ATP competitive CK1δ inhibitors. In particular, a new series of [1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-a][1,3,5]triazines was developed. Some crucial interactors have been identified, such as the presence of a free amino group able to interact with the residues of the hinge region at the 5- and 7- positions of the [1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-a][1,3,5]triazine scaffolds, respectively; or the presence of a 3-hydroxyphenyl or 3,5-dihydroxyphenyl moiety at the 2- position of both nuclei. Molecular modeling studies identified the key interactions involved in the inhibitor-protein recognition process that appropriately fit with the outlined structure-activity relationship. Considering the fact that the CK1 protein kinase is involved in various pathologies in particular of the central nervous system, the interest in the development of new inhibitors permeable to the blood-brain barrier represents today an important goal in the pharmaceutical field. The best potent compound of the series is the 5-(7-amino-5-(benzylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)benzen-1,3-diol (compound 51, IC50 = 0.18 μM) that was predicted to have an intermediate ability to cross the membrane in our in vitro assay and represents an optimal starting point to both studies the therapeutic value of protein kinase CK1δ inhibition and to develop new more potent derivatives.
Bacterial cell walls and membranes provide essential protection for bacteria against environmenta... more Bacterial cell walls and membranes provide essential protection for bacteria against environmental influences. Different bacteria possess different cell envelopes and understanding each of these structures is crucial for the design of effective antibacterial drugs whose targets are intracellular. Optimal properties of drugs that are required for their entry into bacteria are still hard to predict. The guidelines that are suitable and well established for the penetration of a drug into eukaryotic cells are poorly adaptable to the complex world of pathogens. Areas covered: The factors that govern the penetration of anti-infection drugs into bacteria are examined and the available strategies to overcome this therapeutically very important barrier are reviewed. The areas covered include optimization of the physicochemical properties of compounds, utilization of iron-chelating compounds, i.e. siderophores, the use of efflux pump inhibitors, and of carriers such as liposomes. Expert opini...
Introduction: Bacterial cell walls and membranes provide essential protection for bacteria agains... more Introduction: Bacterial cell walls and membranes provide essential protection for bacteria against environmental influences. Different bacteria possess different cell envelopes and understanding each of these structures is crucial for the design of effective antibacterial drugs whose targets are intracel-lular. Optimal properties of drugs that are required for their entry into bacteria are still hard to predict. The guidelines that are suitable and well established for the penetration of a drug into eukaryotic cells are poorly adaptable to the complex world of pathogens. Areas covered: The factors that govern the penetration of anti-infection drugs into bacteria are examined and the available strategies to overcome this therapeutically very important barrier are reviewed. The areas covered include optimization of the physicochemical properties of compounds, utilization of iron-chelating compounds, i.e. siderophores, the use of efflux pump inhibitors, and of carriers such as liposomes. Expert opinion: Although several rules governing permeation have recently been proposed for effective antibacterial drugs, none of them has been so far established as the 'golden' rule. Thus, new research is needed to find a more general approach on how to increase the concentration of antibacterial compounds in bacterial cells.
This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has change... more This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has changed the habits of many young adults, but still the uses of (novel) illicit substances remain high. Drug addiction and tolerance seem to be a major worldwide burden. Multiple drug use is not infrequent and it was associated with a higher incidence of major adverse events than single drug use. The emerging illicit substances will be discussed including their pharmacological effects and their chemical synthesis/structure. The goal of this review is to shed more light on such important aspects of illegality, commonly occurring in urban life. Better drug education, increased law enforcement, and rehabilitation programs should be undertaken to tackle a foremost world burden.
Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide a... more Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide an innovative link between thermoplastics and thermosets. The breakthrough idea behind CANs is to at least partially replace irreversible crosslinks in classic thermoset polymers with dynamic covalent bonds that allow for reversible polymer character and recyclability. Besides, CANs also offer other popular features such as self-healing, weldability, configurability, and shape memory. Most CANs are still petroleum-based, yet shifting toward more sustainable approaches is of the utmost interest. Considering this and the high abundance of lignocellulosic biomass, this perspective focuses on all the research found on lignin-based CANs, including both those starting from fractionated lignin and from lignin-based monomers. This is clearly a new branch within bio-based CANs that holds great potential in various industries. Additionally, some examples of thermoset polymers derived from the same lignin building blocks are given to showcase important chemical transformations that can be used for CANs design in the future. Although CAN design has been extended to many different types of bonds, imines and disulfides largely prevail in the current literature. Lastly, a SWOT (strengths, weaknesses, opportunities, and threats) analysis is presented, considering the performance, competition, opportunities, and drawbacks of lignin-derived CANs.
Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide a... more Covalent adaptable networks (CANs) play an important role in polymer chemistry, as they provide an innovative link between thermoplastics and thermosets. The breakthrough idea behind CANs is to at least partially replace irreversible crosslinks in classic thermoset polymers with dynamic covalent bonds that allow for reversible polymer character and recyclability. Besides, CANs also offer other popular features such as self-healing, weldability, configurability, and shape memory. Most CANs are still petroleum-based, yet shifting toward more sustainable approaches is of the utmost interest. Considering this and the high abundance of lignocellulosic biomass, this perspective focuses on all the research found on lignin-based CANs, including both those starting from fractionated lignin and from lignin-based monomers. This is clearly a new branch within bio-based CANs that holds great potential in various industries. Additionally, some examples of thermoset polymers derived from the same lignin building blocks are given to showcase important chemical transformations that can be used for CANs design in the future. Although CAN design has been extended to many different types of bonds, imines and disulfides largely prevail in the current literature. Lastly, a SWOT (strengths, weaknesses, opportunities, and threats) analysis is presented, considering the performance, competition, opportunities, and drawbacks of lignin-derived CANs.
This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has change... more This mini-review describes recent trends in illicit drug market. The COVID-19 pandemic has changed the habits of many young adults, but still the uses of (novel) illicit substances remain high. Drug addiction and tolerance seem to be a major worldwide burden. Multiple drug use is not infrequent and it was associated with a higher incidence of major adverse events than single drug use. The emerging illicit substances will be discussed including their pharmacological effects and their chemical synthesis/structure. The goal of this review is to shed more light on such important aspects of illegality, commonly occurring in urban life. Better drug education, increased law enforcement, and rehabilitation programs should be undertaken to tackle a foremost world burden.
This review describes, from a chemical point of view, the top “blockbuster” small molecule orphan... more This review describes, from a chemical point of view, the top “blockbuster” small molecule orphan drugs according to their forecasted sales in 2026. Orphan drugs are intended for the treatment, prevention, or diagnosis of a rare disease or condition. These molecules are mostly addressed to the treatment of rare forms of cancer. The respiratory and central nervous systems represent other common therapeutic subcategories. This work will show how the orphan drugs market has significantly grown and will account for a consistent part of prescriptions by 2026.
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
This review describes the recently FDA-approved drugs (in the year 2022). Many of these products ... more This review describes the recently FDA-approved drugs (in the year 2022). Many of these products contain active moieties that FDA had not previously approved, either as a single ingredient or as part of a combination. These products frequently provide important new therapies for patients with multiple unmet diseases. The diverse small molecules are described according to the date of approval and their syntheses is discussed. This review comprises classical chemical scaffolds together with innovative drugs such as a deuterium-containing drug.
This review describes the recent Food and Drug Administration (FDA)-approved drugs (in the year 2... more This review describes the recent Food and Drug Administration (FDA)-approved drugs (in the year 2021) containing at least one halogen atom (covalently bound). The structures proposed throughout this work are grouped according to their therapeutical use. Their synthesis is presented as well. The number of halogenated molecules that are reaching the market is regularly preserved, and 14 of the 50 molecules approved by the FDA in the last year contain halogens. This underlines the emergent role of halogens and, in particular, of fluorine and chlorine in the preparation of drugs for the treatment of several diseases such as viral infections, several types of cancer, cardiovascular disease, multiple sclerosis, migraine and inflammatory diseases such as vasculitis.
Protein kinase CK1δ expression and activity is involved in different pathological situations that... more Protein kinase CK1δ expression and activity is involved in different pathological situations that include neuroinflammatory and neurodegenerative diseases. For this reason, protein kinase CK1δ has become a possible therapeutic target for these conditions. 5,6-fused bicyclic heteroaromatic systems that resemble adenine of ATP represent optimal scaffolds for the development of a new class of ATP competitive CK1δ inhibitors. In particular, a new series of [1,2,4]triazolo[1,5-c]pyrimidines and [1,2,4]triazolo[1,5-a][1,3,5]triazines was developed. Some crucial interactors have been identified, such as the presence of a free amino group able to interact with the residues of the hinge region at the 5- and 7- positions of the [1,2,4]triazolo[1,5-c]pyrimidine and [1,2,4]triazolo[1,5-a][1,3,5]triazine scaffolds, respectively; or the presence of a 3-hydroxyphenyl or 3,5-dihydroxyphenyl moiety at the 2- position of both nuclei. Molecular modeling studies identified the key interactions involved in the inhibitor-protein recognition process that appropriately fit with the outlined structure-activity relationship. Considering the fact that the CK1 protein kinase is involved in various pathologies in particular of the central nervous system, the interest in the development of new inhibitors permeable to the blood-brain barrier represents today an important goal in the pharmaceutical field. The best potent compound of the series is the 5-(7-amino-5-(benzylamino)-[1,2,4]triazolo[1,5-a][1,3,5]triazin-2-yl)benzen-1,3-diol (compound 51, IC50 = 0.18 μM) that was predicted to have an intermediate ability to cross the membrane in our in vitro assay and represents an optimal starting point to both studies the therapeutic value of protein kinase CK1δ inhibition and to develop new more potent derivatives.
Bacterial cell walls and membranes provide essential protection for bacteria against environmenta... more Bacterial cell walls and membranes provide essential protection for bacteria against environmental influences. Different bacteria possess different cell envelopes and understanding each of these structures is crucial for the design of effective antibacterial drugs whose targets are intracellular. Optimal properties of drugs that are required for their entry into bacteria are still hard to predict. The guidelines that are suitable and well established for the penetration of a drug into eukaryotic cells are poorly adaptable to the complex world of pathogens. Areas covered: The factors that govern the penetration of anti-infection drugs into bacteria are examined and the available strategies to overcome this therapeutically very important barrier are reviewed. The areas covered include optimization of the physicochemical properties of compounds, utilization of iron-chelating compounds, i.e. siderophores, the use of efflux pump inhibitors, and of carriers such as liposomes. Expert opini...
Introduction: Bacterial cell walls and membranes provide essential protection for bacteria agains... more Introduction: Bacterial cell walls and membranes provide essential protection for bacteria against environmental influences. Different bacteria possess different cell envelopes and understanding each of these structures is crucial for the design of effective antibacterial drugs whose targets are intracel-lular. Optimal properties of drugs that are required for their entry into bacteria are still hard to predict. The guidelines that are suitable and well established for the penetration of a drug into eukaryotic cells are poorly adaptable to the complex world of pathogens. Areas covered: The factors that govern the penetration of anti-infection drugs into bacteria are examined and the available strategies to overcome this therapeutically very important barrier are reviewed. The areas covered include optimization of the physicochemical properties of compounds, utilization of iron-chelating compounds, i.e. siderophores, the use of efflux pump inhibitors, and of carriers such as liposomes. Expert opinion: Although several rules governing permeation have recently been proposed for effective antibacterial drugs, none of them has been so far established as the 'golden' rule. Thus, new research is needed to find a more general approach on how to increase the concentration of antibacterial compounds in bacterial cells.
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