Difluorocarbene Enabled to Access 1,3-oxazin-6-ones from Enamides

Abstract2-Fluoroindoles as an important structural scaffold are widely existing in many bioactive or therapeutic agents. Despite their potential usefulness, efficient constructions of 2-fluoroindole derivatives are very sparce. The development of straightforward synthetic approaches to access 2-fluoroindoles is highly desirable for studying their fundamental properties and applications. Herein, we report an efficient and general strategy for the construction of 2-fluoroindoles in which a wide variety of 2-fluoroindoles were accessed with high efficiency and chemoselectivity. Instead of starting from indole skeletons, our strategy constructs indole scaffolds alongside the incorporation of fluorine atom on C2 position in a formal [4+1] cyclization from readily accessible ortho-vinylanilines and difluorocarbene. In our protocol, commercially accessible halodifluoroalkylative reagents provide one carbon and one fluorine atom by cleaving one C-N tertiary bond and forming one C-N bond and one C-C double bond with ortho-vinylanilines. Downstream transformations on 2-fluoroindoles lead to various valuable bioactive molecules which demonstrated significant synthetic advantages over previous reports. And mechanistic studies suggest that the reaction undergoes a cascade difluorocarbene-trapping and intramolecular Michael addition reaction followed by Csp3-F bond cleavage.

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Synthetic and Biological Attributes of Pyrimidine Derivatives: A Recent update

Current Organic Synthesis ◽

10.2174/1570179418666210706152515 ◽

2021 ◽

Vol 18 ◽

Author(s):

Meenu Devi ◽

Shivangi Jaiswal ◽

Sonika Jain ◽

Navjeet Kaur ◽

Jaya Dwivedi

Keyword(s):

Biological Activities ◽

Structural Diversity ◽

Therapeutic Agents ◽

Pyrimidine Derivatives ◽

Diverse Range ◽

Biological Attributes ◽

Synthetic Approaches ◽

High Degree ◽

Therapeutic Activities ◽

Anti Hiv

: Nitrogen-containing heterocycles attract the attention of chemists due to their multifarious activities. Amongst all, pyrimidine plays a central role and exhibits a broad spectrum of biological activities. Literature is replete with the various aspects of synthetic development in pyrimidine chemistry for a wide array of applications. It aroused our interest to compile various novel and efficient synthetic approaches towards the synthesis of pyrimidine and its derivatives. Pyrimidine derivatives are broadly useful as therapeutic agents, owing to their high degree of structural diversity. They have been recorded to possess a diverse range of therapeutic activities, viz. anticancer, anti-inflammatory, anti-HIV etc.

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Fused Heterocyclic Systems with an s-Triazine Ring. 34. Development of a Practical Approach for the Synthesis of 5-Aza-isoguanines

Molecules ◽

10.3390/molecules24081453 ◽

2019 ◽

Vol 24 (8) ◽

pp. 1453

Author(s):

Junaid ◽

Lim ◽

Zhou ◽

Chui ◽

Dolzhenko

Keyword(s):

Anticancer Agents ◽

Purine Nucleoside Phosphorylase ◽

Practical Method ◽

Therapeutic Agents ◽

Ring Closure ◽

Triazine Ring ◽

Significant Difference ◽

Synthetic Approaches ◽

General Method ◽

Intramolecular Ring

Purine isosteres present excellent opportunities in drug design and development. Using isosteres of natural purines as scaffolds for the construction of new therapeutic agents has been a valid strategy of medicinal chemistry. Inspired by the similarity to isoguanine, we attempted to develop a practical method for the preparation of 5-aza-isoguanines. Several synthetic approaches were explored to establish a robust general protocol for the preparation of these compounds. The significant difference in the reactivity of the C-5 and C-7 electrophilic centers of 1,2,4-triazolo[1,5-a][1,3,5]triazines (5-azapurines) towards nucleophiles was demonstrated. The most practical and general method for the preparation of 5-aza-isoguanines involved a regioselective reaction of ethoxycarbonyl isothiocyanate with a 5-aminotriazole. The intramolecular ring closure of the resulted product followed by the S-methylation afforded 7-methylthio-2-phenyl-1,2,4-triazolo[1,5-a][1,3,5]triazin-5-one, which could be effectively aminated with various amines. The resulted 5-aza-isoguanines resemble a known purine nucleoside phosphorylase inhibitor and could be interesting for further investigations as potential anticancer agents.

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Fluorinated phenylalanines: synthesis and pharmaceutical applications

Beilstein Journal of Organic Chemistry ◽

10.3762/bjoc.16.91 ◽

2020 ◽

Vol 16 ◽

pp. 1022-1050 ◽

Cited By ~ 2

Author(s):

Laila Fathy Awad ◽

Mohammed Salah Ayoup

Keyword(s):

Amino Acids ◽

Drug Research ◽

Enzyme Inhibitors ◽

Therapeutic Proteins ◽

Aromatic Amino Acids ◽

Therapeutic Agents ◽

Synthetic Methods ◽

Pharmaceutical Applications ◽

Recent Advances ◽

Synthetic Approaches

Recent advances in the chemistry of peptides containing fluorinated phenylalanines (Phe) represents a hot topic in drug research over the last few decades. ᴅ- or ʟ-fluorinated phenylalanines have had considerable industrial and pharmaceutical applications and they have been expanded also to play an important role as potential enzyme inhibitors as well as therapeutic agents and topography imaging of tumor ecosystems using PET. Incorporation of fluorinated aromatic amino acids into proteins increases their catabolic stability especially in therapeutic proteins and peptide-based vaccines. This review seeks to summarize the different synthetic approaches in the literature to prepare ᴅ- or ʟ-fluorinated phenylalanines and their pharmaceutical applications with a focus on published synthetic methods that introduce fluorine into the phenyl, the β-carbon or the α-carbon of ᴅ-or ʟ-phenylalanines.

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Water-soluble amphiphilic ruthenium(ii) polypyridyl complexes as potential light-activated therapeutic agents

Chemical Communications ◽

10.1039/d0cc04397d ◽

2020 ◽

Vol 56 (65) ◽

pp. 9332-9335

Author(s):

Sandra Estalayo-Adrián ◽

Salvador Blasco ◽

Sandra A. Bright ◽

Gavin J. McManus ◽

Guillermo Orellana ◽

...

Keyword(s):

Cervical Cancer ◽

Cancer Cells ◽

Cellular Uptake ◽

Therapeutic Agents ◽

Water Soluble ◽

Polypyridyl Complexes ◽

Cervical Cancer Cells

Two new water-soluble amphiphilic Ru(ii) polypyridyl complexes were synthesised and their photophysical and photobiological properties evaluated; both complexes showed a rapid cellular uptake and phototoxicity against HeLa cervical cancer cells.

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Pyridyl disulfide-based thiol–disulfide exchange reaction: shaping the design of redox-responsive polymeric materials

Polymer Chemistry ◽

10.1039/d0py01215g ◽

2020 ◽

Vol 11 (48) ◽

pp. 7603-7624

Author(s):

Ismail Altinbasak ◽

Mehmet Arslan ◽

Rana Sanyal ◽

Amitav Sanyal

Keyword(s):

Exchange Reaction ◽

Functional Materials ◽

Polymeric Materials ◽

Disulfide Exchange ◽

Redox Responsive ◽

Synthetic Approaches

This review provides an overview of synthetic approaches utilized to incorporate the thiol-reactive pyridyl-disulfide motif into various polymeric materials, and briefly highlights its utilization to obtain functional materials.

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Flavonoids in adipose tissue inflammation and atherosclerosis: one arrow, two targets

Clinical Science ◽

10.1042/cs20200356 ◽

2020 ◽

Vol 134 (12) ◽

pp. 1403-1432 ◽

Cited By ~ 2

Author(s):

Manal Muin Fardoun ◽

Dina Maaliki ◽

Nabil Halabi ◽

Rabah Iratni ◽

Alessandra Bitto ◽

...

Keyword(s):

Adipose Tissue ◽

Fruits And Vegetables ◽

Metabolic Diseases ◽

Therapeutic Agents ◽

Adipose Tissue Inflammation ◽

Cellular Mechanisms ◽

Tissue Inflammation ◽

Cholesterol Levels ◽

Naturally Occurring ◽

Pro Inflammatory Cytokines

Abstract Flavonoids are polyphenolic compounds naturally occurring in fruits and vegetables, in addition to beverages such as tea and coffee. Flavonoids are emerging as potent therapeutic agents for cardiovascular as well as metabolic diseases. Several studies corroborated an inverse relationship between flavonoid consumption and cardiovascular disease (CVD) or adipose tissue inflammation (ATI). Flavonoids exert their anti-atherogenic effects by increasing nitric oxide (NO), reducing reactive oxygen species (ROS), and decreasing pro-inflammatory cytokines. In addition, flavonoids alleviate ATI by decreasing triglyceride and cholesterol levels, as well as by attenuating inflammatory mediators. Furthermore, flavonoids inhibit synthesis of fatty acids and promote their oxidation. In this review, we discuss the effect of the main classes of flavonoids, namely flavones, flavonols, flavanols, flavanones, anthocyanins, and isoflavones, on atherosclerosis and ATI. In addition, we dissect the underlying molecular and cellular mechanisms of action for these flavonoids. We conclude by supporting the potential benefit for flavonoids in the management or treatment of CVD; yet, we call for more robust clinical studies for safety and pharmacokinetic values.

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Antithrombotic Therapy for DVT/PE

Hämostaseologie ◽

10.1055/s-0038-1659983 ◽

1997 ◽

Vol 17 (03) ◽

pp. 161-162

Author(s):

Thomas Hyers

Keyword(s):

Molecular Weight ◽

Low Molecular Weight Heparin ◽

Oral Anticoagulants ◽

Cost Effective ◽

Therapeutic Agents ◽

Great Promise ◽

Term Therapy ◽

Low Molecular Weight ◽

Long Term Therapy

SummaryProblems with unfractionated heparin as an antithrombotic have led to the development of new therapeutic agents. Of these, low molecular weight heparin shows great promise and has led to out-patient therapy of DVT/PE in selected patients. Oral anticoagulants remain the choice for long-term therapy. More cost-effective ways to give oral anticoagulants are needed.

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Imaging of central cannabinoid CB1 receptors, a potential target for therapeutic agents in movement disorders

Aktuelle Neurologie ◽

10.1055/s-2005-916290 ◽

2005 ◽

Vol 32 (06) ◽

Author(s):

G Berding ◽

U Schneider ◽

P Gielow ◽

R Buchert ◽

WH Knapp ◽

...

Keyword(s):

Movement Disorders ◽

Therapeutic Agents ◽

Cb1 Receptors ◽

Potential Target

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Non-Steroidal Anti-inflammatory Drugs (NSAIDs): Synthesis of Ibuprofen, Naproxen and Nabumetone

Al Mustansiriyah Journal of Pharmaceutical Sciences ◽

10.32947/ajps.19.03.0409 ◽

2019 ◽

pp. 19-27

Keyword(s):

Review Paper ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Synthetic Approaches

This review paper covers the major synthetic approaches attempted towards the synthesis of some Non-Steroidal Anti-Inflammatory Drugs (Naproxen, Ibuprofen and Nabumetone)

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