scholarly journals Fluorination methods in drug discovery

2016 ◽  
Vol 14 (36) ◽  
pp. 8398-8427 ◽  
Author(s):  
Damian E. Yerien ◽  
Sergio Bonesi ◽  
Al Postigo
Keyword(s):  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Late Stage ◽  
Biologically Active ◽  
Metabolic Degradation

Late stage fluorination methods applied to biologically-active drugs have provided the pharmaceutical industry with new leads that show improved properties such as modulation of lipophilicity, electronegativity, basicity, bioavailability, and deceleration of metabolic degradation.

scholarly journals Exploring Electrochemical C(sp3)–H Oxidation for the Late-Stage Methylation of Complex Molecules

2021 ◽  
Author(s):  
Song Lin ◽  
Luiz Novaes ◽  
Justin Ho ◽  
Kaining Mao ◽  
Kaida Liu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Late Stage ◽  
De Novo ◽  
Reaction System ◽  
Biologically Active ◽  
Complex Molecules ◽  
Synthetic Strategy ◽  
Mechanistic Analysis ◽  
Methyl Effect ◽  
Operational Simplicity

The “magic methyl” effect – a dramatic boost in the potency of biologically active compounds from the incorporation of a single methyl group – provides a simple yet powerful strategy employed by medicinal chemists in the drug discovery process. Despite significant advances, methodologies that enable the selective C(sp3)–H methylation of structurally complex medicinal agents remain very limited. In this work, we disclose a modular, efficient, and selective strategy for the α-methylation of protected amines (i.e., amides, carbamates, and sulfonamides) by means of electrochemical oxidation. Mechanistic analysis guided our development of an improved electrochemical protocol on the basis of the classic Shono oxidation reaction, which features broad reaction scope, high functional group compatibility, and operational simplicity. Importantly, this reaction system is amenable to the late-stage functionalization of complex targets containing basic nitrogen groups that are prevalent in medicinally active agents. When combined with organozinc-mediated C–C bond formation, our protocol enabled the direct methylation of a myriad of amine derivatives including those that have previously been explored for the “magic methyl” effect. This synthetic strategy thus circumvents multistep de novo synthesis that is currently necessary to access such compounds and has the potential to accelerate drug discovery efforts.

scholarly journals Exploring Electrochemical C(sp3)–H Oxidation for the Late-Stage Methylation of Complex Molecules

2021 ◽  
Author(s):  
Song Lin ◽  
Luiz Novaes ◽  
Justin Ho ◽  
Kaining Mao ◽  
Kaida Liu ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Late Stage ◽  
De Novo ◽  
Reaction System ◽  
Biologically Active ◽  
Complex Molecules ◽  
Synthetic Strategy ◽  
Mechanistic Analysis ◽  
Methyl Effect ◽  
Operational Simplicity

The “magic methyl” effect – a dramatic boost in the potency of biologically active compounds from the incorporation of a single methyl group – provides a simple yet powerful strategy employed by medicinal chemists in the drug discovery process. Despite significant advances, methodologies that enable the selective C(sp3)–H methylation of structurally complex medicinal agents remain very limited. In this work, we disclose a modular, efficient, and selective strategy for the α-methylation of protected amines (i.e., amides, carbamates, and sulfonamides) by means of electrochemical oxidation. Mechanistic analysis guided our development of an improved electrochemical protocol on the basis of the classic Shono oxidation reaction, which features broad reaction scope, high functional group compatibility, and operational simplicity. Importantly, this reaction system is amenable to the late-stage functionalization of complex targets containing basic nitrogen groups that are prevalent in medicinally active agents. When combined with organozinc-mediated C–C bond formation, our protocol enabled the direct methylation of a myriad of amine derivatives including those that have previously been explored for the “magic methyl” effect. This synthetic strategy thus circumvents multistep de novo synthesis that is currently necessary to access such compounds and has the potential to accelerate drug discovery efforts.

Oxazole-Based Compounds As Anticancer Agents

2020 ◽  
Vol 26 (41) ◽  
pp. 7337-7371 ◽  
Author(s):  
Maria A. Chiacchio ◽  
Giuseppe Lanza ◽  
Ugo Chiacchio ◽  
Salvatore V. Giofrè ◽  
Roberto Romeo ◽  
...  
Keyword(s):  
Cancer Research ◽  
Drug Discovery ◽  
Anticancer Agents ◽  
Heterocyclic Compounds ◽  
Chemical Diversity ◽  
Biologically Active ◽  
New Drugs ◽  
The Core ◽  
Anti Cancer ◽  
Biologically Active Derivatives

: Heterocyclic compounds represent a significant target for anti-cancer research and drug discovery, due to their structural and chemical diversity. Oxazoles, with oxygen and nitrogen atoms present in the core structure, enable various types of interactions with different enzymes and receptors, favoring the discovery of new drugs. Aim of this review is to describe the most recent reports on the use of oxazole-based compounds in anticancer research, with reference to the newly discovered iso/oxazole-based drugs, to their synthesis and to the evaluation of the most biologically active derivatives. The corresponding dehydrogenated derivatives, i.e. iso/oxazolines and iso/oxazolidines, are also reported.

Late-stage C–H functionalization offers new opportunities in drug discovery

2021 ◽  
Author(s):  
Lucas Guillemard ◽  
Nikolaos Kaplaneris ◽  
Lutz Ackermann ◽  
Magnus J. Johansson
Keyword(s):  
Drug Discovery ◽  
Late Stage

Synthesis of Pyrazolofuropyrazine via One-Pot SNAr Reaction and Intramolecular Direct C–H Arylation

Synthesis ◽  
2018 ◽  
Vol 50 (07) ◽  
pp. 1493-1498 ◽  
Author(s):  
Shinichiro Fuse ◽  
Hiroyuki Nakamura ◽  
Megumi Inaba ◽  
Shinichi Sato ◽  
Manjusha Joshi
Keyword(s):  
Drug Discovery ◽  
Rapid Development ◽  
Ring System ◽  
Biologically Active ◽  
Drug Candidate ◽  
One Pot ◽  
Ring Systems ◽  
Drug Candidates ◽  
Fused Ring ◽  
Snar Reaction

Fused-ring systems containing heterocycles are attractive templates for drug discovery. Biologically active 6-5-5+6 fused-ring systems that possess heterocycles are available, but these require a relatively large number of synthetic steps for preparation. Therefore, pyrazolofuropyrazine was designed as a 6-5-5+6 ring system template that incorporates ready accessibility for drug discovery. Pyrazolofuropyrazines were successfully constructed in only a few steps via one-pot SNAr reaction/intramolecular C–H direct arylation. As a drug candidate, pyrazolofuropyrazine has earned a favorable LogP, although significant biological activity has yet to be established; the ready accessibility of pyrazolofuropyrazine template, however, offers an opportunity for the rapid development of promising new drug candidates.

scholarly journals Currently Available Strategies for Target Identification of Bioactive Natural Products

2021 ◽  
Vol 9 ◽  
Author(s):  
Gen Li ◽  
Xuling Peng ◽  
Yajing Guo ◽  
Shaoxuan Gong ◽  
Shijie Cao ◽  
...  
Keyword(s):  
Natural Products ◽  
Pharmaceutical Industry ◽  
Drug Research ◽  
Target Identification ◽  
Biologically Active ◽  
Bioactive Natural Products ◽  
Target Sites ◽  
Wide Availability ◽  
Research Findings ◽  
Active Natural

In recent years, biologically active natural products have gradually become important agents in the field of drug research and development because of their wide availability and variety. However, the target sites of many natural products are yet to be identified, which is a setback in the pharmaceutical industry and has seriously hindered the translation of research findings of these natural products as viable candidates for new drug exploitation. This review systematically describes the commonly used strategies for target identification via the application of probe and non-probe approaches. The merits and demerits of each method were summarized using recent examples, with the goal of comparing currently available methods and selecting the optimum techniques for identifying the targets of bioactive natural products.

Drug Discovery

2018 ◽  
pp. 399-404
Author(s):  
S. Nassir Ghaemi
Keyword(s):  
Drug Discovery ◽  
Pharmaceutical Industry ◽  
Discovery Process ◽  
Drug Discovery Process ◽  
New Approach ◽  
The Past ◽  
Scientific Exploration ◽  
Clinical Indications ◽  
The Future ◽  
Clinical Diagnoses

Newer and better medications are obtained as part of the drug discovery process, which occurs mainly in the pharmaceutical industry. This process is hampered by excessive attention to marketing demands, as opposed to scientific exploration. It also is impaired by the psychiatric profession’s mistaken ideologies, whether psychoanalytic orthodoxy in the past or DSM beliefs of the present. Wrong clinical phenotypes impair finding new pharmacological mechanisms and targeting them well to the write clinical indications. Perhaps as a consequence, no treatments have been developed in the last few decades, since DSM-III, that are more effective than prior agents. Progress for the future in drug discovery will require not just better neurobiological work, but also a new approach to clinical diagnoses in psychiatry.

scholarly journals Modular synthesis of α-fluorinated arylmethanes via desulfonylative cross-coupling

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Masakazu Nambo ◽  
Jacky C.-H. Yim ◽  
Luiza B. O. Freitas ◽  
Yasuyo Tahara ◽  
Zachary T. Ariki ◽  
...  
Keyword(s):  
Biological Activity ◽  
Late Stage ◽  
Recent Progress ◽  
Cross Coupling ◽  
Biologically Active Compounds ◽  
Biologically Active ◽  
Active Compounds ◽  
Arylboronic Acids ◽  
Modular Synthesis ◽  
Synthetic Routes

Abstract α-Fluoromethylarenes are common substructures in pharmaceuticals and agrochemicals, with the introduction of fluorine often resulting in improved biological activity and stability. Despite recent progress, synthetic routes to α-fluorinated diarylmethanes are still rare. Herein we describe the Pd-catalyzed Suzuki-Miyaura cross-coupling of α-fluorinated benzylic triflones with arylboronic acids affording structurally diverse α-fluorinated diarylmethanes. The ease of synthesis of fluorinated triflones as the key starting materials enables powerful late-stage transformations of known biologically active compounds into fluorinated analogs.

The Potential of Biologically Active Brazilian Plant Species as a Strategy to Search for Molecular Models for Mosquito Control

Planta Medica ◽  
2020 ◽  
Author(s):  
Marilia Valli ◽  
Letícia Cristina Vieira Atanázio ◽  
Gustavo Claro Monteiro ◽  
Roberta Ramos Coelho ◽  
Daniel Pecoraro Demarque ◽  
...  
Keyword(s):  
Natural Products ◽  
Drug Discovery ◽  
Vector Control ◽  
Plant Species ◽  
Mosquito Control ◽  
Biologically Active ◽  
Molecular Models ◽  
Public Health Importance ◽  
Active Compounds ◽  
Brazilian Biodiversity

AbstractNatural products are a valuable source of biologically active compounds and continue to play an important role in modern drug discovery due to their great structural diversity and unique biological properties. Brazilian biodiversity is one of the most extensive in the world and could be an effective source of new chemical entities for drug discovery. Mosquitoes are vectors for the transmission of dengue, Zika, chikungunya, yellow fever, and many other diseases of public health importance. These diseases have a major impact on tropical and subtropical countries, and their incidence has increased dramatically in recent decades, reaching billions of people at risk worldwide. The prevention of these diseases is mainly through vector control, which is becoming more difficult because of the emergence of resistant mosquito populations to the chemical insecticides. Strategies to provide efficient and safe vector control are needed, and secondary metabolites from plant species from the Brazilian biodiversity, especially Cerrado, that are biologically active for mosquito control are herein highlighted. Also, this is a literature revision of targets as insights to promote advances in the task of developing active compounds for vector control. In view of the expansion and occurrence of arboviruses diseases worldwide, scientific reviews on bioactive natural products are important to provide molecular models for vector control and contribute with effective measures to reduce their incidence.

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